In recent years, long-term prognostic observations of five years or more for early-stage lung cancer have revealed that deaths from other diseases (secondary cancer deaths+non-cancer deaths) account for a considerable proportion of all deaths. In the era of medical advances, achieving a survival of five years after surgery is not the only goal for early-stage lung cancer, for which a good long-term prognosis can be expected. In the future, details of other disease deaths, i.e. what kind of cancer the patients suffered from and what kind of treatment they received in cases of death due to secondary cancers, or what kind of disease led to death due to non-cancer disease, should be confirmed over a much longer period of time than before. Given the above, we thoracic oncologists should evaluate how surgery, adjuvant chemotherapy, or adjuvant radiotherapy affect the long-term events (more than five years after treatment) and re-consider and improve our current treatment strategy properly.

Objective. This study clarified the details concerning sarcopenia as a comorbidity and the relationship between sarcopenia and the prognosis in patients with advanced non-small-cell lung cancer. Study Design. We retrospectively studied 39 patients with stage IV advanced non-small-cell lung cancer and an Eastern Cooperative Oncology Group Performance Status of 0-1. After classifying patients into the non-sarcopenia or sarcopenia group based on their grip strength, gait speed, and psoas muscle index, the proportion in the sarcopenia group was determined. The overall survival (OS) was then compared between patients with and without sarcopenia and by the severity of sarcopenia. Results. Sarcopenia was a comorbidity in 41%, and the sarcopenia group had a significantly worse OS than the non-sarcopenia group (median, 11.0 vs. 17.9 months, p<0.05). Furthermore, the OS decreased with increasing severity of sarcopenia (log-rank test for trend, p<0.05). Conclusion. In advanced non-small-cell lung cancer, the rate of sarcopenia comorbidity is high, even in patients with a good Performance Status, and an accurate evaluation of sarcopenia is necessary to predict the prognosis.

Objective. Mesothelioma patients can apply to the Industrial Accident Compensation Insurance System. However, the evaluation of occupational exposure is a heavy load for physicians. The current status of asbestos exposure interviews has not been clarified. Study Design. A questionnaire survey was conducted on patients, and a stepwise regression analysis was conducted with application (certification) for Industrial Accident Compensation Insurance System as the dependent variable and three "physician's response" items and five "reasons for application for Industrial Accident Compensation Insurance System" items as independent variables. Results. Patients were more likely to apply for workers' compensation insurance when they received more information from their physicians (b=0.276, t[88]=2.336, p=0.021, β=0.242). We also found an increase in applications for Industrial Accident Compensation Insurance System when there was an increase in advice and suggestions from patient groups (b=0.569, t[88]=5.373, p<0.05, β=0.497). Conclusion. It is important to inform patients about applying to the Industrial Accident Compensation Insurance System, and it is necessary to establish a consultation support system at medical institutions and to deepen cooperation with patient groups.

Objective. We verified the usefulness of a new next-generation sequencing modality with the Lung Cancer Compact Panel™ using cytological specimens. Study Design. From December 2021 to February 2022, the wash fluid of lung tumors from 10 patients obtained using endobronchial ultrasonography (EBUS) with a guide sheath (GS), EBUS transbronchial needle aspiration (EBUS-TBNA), and pleural effusion puncture was examined with the Lung Cancer Compact Panel™. We examined the patients' medical records to obtain information on the analysis success rate and detection rate of gene mutations in consecutive cases searched for driver gene mutations. Results. Ten patients (6 lung adenocarcinoma, and 1 each of lung squamous cell carcinoma, small-cell lung cancer, renal cell carcinoma, and organizing pneumonia) and 12 samples (7 from brushing, 2 from EBUS-TBNA, 1 from a transbronchial biopsy [TBB] plus brushing, 1 from a TBB, and 1 from brushing) were examined using the Lung Cancer Compact Panel™. We successfully analyzed all tests in all 10 patients (100%). EGFR L858R, KRAS G12D, or KRAS G12V was detected in lung adenocarcinoma patients. KRAS G12V was detected in the lung squamous cell carcinoma patient. The amounts of nucleic acids from the pleural effusion puncture and EBUS-TBNA were sufficient for the analyses. Conclusion. The Lung Cancer Compact Panel™ was useful for detecting gene mutations using cytological specimens.

Background. Pulmonary pleomorphic carcinoma, a subtype of sarcomatoid carcinoma, is a rare lung malignancy. This cancer is usually resistant to chemo- and radiotherapy, and no standard treatment protocols are currently available. We herein report a case of sarcomatoid carcinoma in a patient who responded to combination therapy using nivolumab plus ipilimumab. Case. A 62-year-old man who was a current smoker was referred to our hospital with right lower extremity paresis. Computed tomography revealed a mass in the right upper lung, and magnetic resonance imaging showed multiple brain metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of the mass revealed sarcomatoid carcinoma with a low expression of programmed cell death ligand-1 (PD-L1), and the tumor proportion score was 10%, being classified as clinical stage IVB (cT3N0M1c [BRA]). Following stereotactic radiotherapy to the brain lesions, he was administered combination immunotherapy using nivolumab (360 mg/kg every 3 weeks) and ipilimumab (1 mg/kg every 6 weeks). We observed shrinkage of both lung and brain lesions, which was considered a partial response, and he showed only mild immunotherapy-induced toxicity. Conclusion. Immune checkpoint inhibitors may serve as an effective therapeutic option in patients with sarcomatoid carcinoma; combination therapy using these agents may provide an improved therapeutic benefit in such cases.

Background. Anaplastic lymphoma kinase (ALK) rearrangement is a rare subset of squamous cell lung cancer (SCC). The efficacy of ALK-tyrosine kinase inhibitors (TKIs) in ALK-rearranged SCC patients remains unclear. Case. A 49-year-old Japanese woman presented to our hospital with symptoms of cough and supraclavicular fossa lymph node swelling. She was diagnosed with SCC (cT4N3M1c, cStage IVB) by a percutaneous core needle biopsy from the supraclavicular fossa lymph node. As the patient was a non-smoking woman, and the progression of the disease was rapid, we suspected the presence of an oncogenic driver. Immunostaining and fluorescence in situ hybridization revealed the presence of an ALK fusion gene. Cytotoxic chemotherapy was not feasible because the patient was suffering from idiopathic thrombocytopenic purpura. She was therefore treated with sequential ALK-TKI therapy involving alectinib, brigatinib, and lorlatinib. The tumors decreased in size with these treatments, but the duration of the effect was shorter than expected, and she ultiamtly died 12 months after the diagnosis. Conclusion. ALK-TKIs are treatment options for ALK-rearranged SCC patients; however, their efficacy is limited. Molecular testing for the ALK fusion gene is recommended even in SCC if the patient has a background that suggests the presence of an oncogenic driver.

Background. Lung cancer is a rare complication of pregnancy. Lung cancer may be diagnosed at an advanced stage because respiratory symptoms can be mistakenly perceived as pregnancy-related, and radiological examinations will probably be avoided due to concerns regarding fetal exposure. Case. A pregnant woman in her late thirties complained of cough that started from approximately the 26^th week of gestation, gradually resulting in dyspnea and appetite loss. Because a chest X-ray performed during the 37^th week of gestation revealed opacity in the entire left lung field, she was immediately admitted to our hospital. Computed tomography revealed total atelectasis of the left lung accompanied by pleural effusion, bilateral hilar and mediastinal lymphadenopathies, and multiple nodular shadows in the right lung. Considering the possibility of carcinomatous pleuritis due to lung cancer, continuous suction drainage of the left pleural effusion was immediately initiated. The following day, her infant was delivered via cesarean section. Pathological and genetic examinations of the pleural effusion sample demonstrated adenocarcinoma and rearrangement of the anaplastic lymphoma kinase (ALK) gene. After initiating alectinib treatment on the 5^th day of hospitalization, the tumor promptly decreased in size and the therapeutic effect has been maintained for more than 1 year. No malignant tumors or developmental anomalies have been observed in her infant. Conclusion. Lung cancer in women of reproductive age is characterized by a relatively high frequency of harboring certain driver gene mutations, which can progress rapidly. Thus, chest X-ray imaging should be performed for patients with persistent respiratory symptoms. Additionally, considering the possibility of the transmission of maternal cancer to offspring, pathological examinations of the mother's placenta and postnatal follow-up of the infant are important.

Background. Markers are required for partial resection of tumors that are difficult to identify intraoperatively. Virtual-assisted lung mapping (VAL-MAP) achieves simultaneous multiple mapping on the lung surface, enabling the resection range to be simulated more accurately than with conventional marking. Indocyanine green (ICG) gives good visibility as the dye used in VAL-MAP. However, since VAL-MAP cannot be used as a central side marker, there is a risk of the surgical margin of the central side closing. We attempted to use ICG injected into the bronchial wall as a central side marker. Case. In an 87-year-old woman who had undergone right lung S¹⁺²a segmentectomy for adenocarcinoma six years earlier, a new ground-glass nodule appeared, and wedge resection was planned for the diagnosis and treatment. Three mappings were placed on the lung surface using ICG-VAL-MAP, and ICG was injected into the bronchial wall of B⁴b on the central side of the tumor. During the operation, the bronchial-injected ICG was confirmed in the interlobar fissure with near-infrared fluorescence imaging, and wedge resection was performed using this as a deep marker. The resection margin was 2.2 cm. No adverse events were observed. Conclusion. ICG injected into the bronchial wall can serve as a central side marker.

Background. Two cycles of chemotherapy and nivolumab, an anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, have been used as the standard therapy for advanced or recurrent non-small cell lung cancer. Clinical trials have demonstrated a significantly higher overall survival with this combination than with chemotherapy alone. However, the management of adverse events is important, as with any other regimen. Case. A 61-year-old man complaining of dyspnea was diagnosed with right upper lobe non-small cell lung cancer (cT4N2M0 cStage IIIB, PD-L1 TPS 15%). Combination therapy of carboplatin, paclitaxel, nivolumab, and ipilimumab was started, and by day 10 of treatment, the tumor had clearly shrunk on chest radiographs. During day 22 of the administration of nivolumab, the patient experienced generalized erythema and nasal obstruction, which was determined to be an infusion-related reaction (IRR) grade 2. Hydrocortisone and H1 and H2 blockers were administered, and the patient's symptoms rapidly improved. Immediately after restarting nivolumab, the patient experienced wheezing, hypotension, and loss of consciousness, leading to cardiopulmonary arrest. The patient did not respond to repeated intravenous adrenaline administration; therefore, he was intubated and placed on an extracorporeal membrane artificial lung (V-A ECMO), which resulted in the resumption of his pulse. Subsequently, the patient was treated with steroids and discharged without any significant complications. Conclusions. Although the frequency of grade ≥3 IRR is quite low with this combination treatment, clinicians should be aware that it remains a distinct possibility.

Background. Lung typical carcinoids with spontaneous regression or paraneoplastic syndromes other than carcinoid syndromes are relatively rare. Case. A 69-year-old man was found to have a chest abnormality during a medical checkup. Chest computed tomography (CT) showed nodules in the right S⁵ and 8/9th intercostal space and a mass in the right parietal pleura, near the 9-10th thoracic spine. The paravertebral mass regressed on chest CT, but right pleural effusion appeared three months later. He was transferred to our hospital and found to have peripheral eosinophilia and eosinophilic pleural effusion. A CT-guided biopsy was performed, as chest CT showed an increase in the size of the nodule at the right chest wall. However, the diagnosis was difficult due to an insufficient sample volume, and thoracoscopic partial lung resection with pleural tumor resection was performed. The histopathological samples showed tumor cells that were positive for neuroendocrine markers. The cell division was extremely low, and the patient was diagnosed with lung typical carcinoid (pT1cN0M1a pStage IVA). After resection, the peripheral eosinophilia improved spontaneously, and the right pleural effusion did not relapse. Despite the advanced stage, the target lesion was resected, and careful follow-up is being conducted. Conclusion. We experienced a very rare case of a patient with lung typical carcinoid with spontaneous regression and paraneoplastic syndromes.

Background. Antiretroviral therapy has been introduced to improve the prognosis of patients with human immunodeficiency virus (HIV) infection, and as a result, non-AIDS-defining cancer (NADC) may affect the prognosis. It has been shown that lung cancer patients with HIV progress faster in comparison to patients without HIV, and have a poor prognosis; however, there is no specific treatment protocol for lung cancer in patients with HIV. Case. The patient was a 55-year-old man who was diagnosed with advanced lung adenocarcinoma and infected with HIV. Platinum-based chemotherapy was administered, but the effect was poor, and docetaxel was started as the next treatment. He then showed prolonged myelosuppression, and his general condition worsened, making it difficult to continue chemotherapy. Conclusion. We report a case of advanced lung cancer in a patient with HIV infection. It is hoped that standard chemotherapy for advanced lung cancer with HIV infection will be established.

Background. Alectinib is an effective and well-tolerated agent for treating anaplastic lymphoma kinase (ALK) fusion gene-positive lung adenocarcinoma. However, treatment with alectinib results in interstitial lung disease (ILD) as an adverse effect, thereby precluding therapy continuation. Several other ALK inhibitors have been studied in clinical trials, and brigatinib is the most recent ALK inhibitor approved in Japan. No reports of patients with ALK fusion gene-positive lung adenocarcinoma successfully treated with brigatinib after alectinib-induced ILD exist, but we herein report two such cases. Cases. Two patients with ALK fusion gene-positive lung adenocarcinoma treated with alectinib developed Common Terminology Criteria for Adverse Events version 5.0 grade 2 and grade 3 ILD (one each). After ILD improvement, treatment with brigatinib was initiated. One patient showed an antitumor effect without ILD recurrence, and the other older patient showed ILD recurrence. ILD disappeared only after withdrawing brigatinib, and a reduced dose produced an antitumor effect without ILD recurrence. Conclusion. In cases of alectinib-induced ILD, switching to brigatinib is a possible therapeutic option. However, patients with a history of ILD in response to ALK inhibitors should be followed carefully.

Background. Retroperitoneal fibrosis is characterized by fibrosis around the abdominal aorta and iliac arteries. Two-thirds of reported cases had idiopathic causes. Idiopathic retroperitoneal fibrosis is thought to result from a local inflammatory reaction to antigens in the atherosclerotic plaques of the abdominal aorta. Therefore, it is thought that idiopathic retroperitoneal fibrosis may be a manifestation of a systemic autoimmune or inflammatory disease. In contrast, anti-programmed cell death 1 (anti-PD-1) antibodies may overexpress innate immunity. There have been only two case reports on retroperitoneal fibrosis during anti-PD-1 antibody treatment. We encountered two cases of retroperitoneal fibrosis during anti-PD-1 antibody treatment. Cases. Case 1 involved a 57-year-old man who experienced recurrence of squamous cell lung carcinoma after resection. More than 75% of his cancer cells were positive for programmed cell death ligand 1 (PD-L1). He experienced urinary urgency after one year and six months of nivolumab treatment. Computed tomography revealed a homogeneous plaque that was isodense with muscle surrounding the abdominal aorta and iliac arteries. Positron emission tomography revealed the accumulation of fluorodeoxyglucose at the same site. The serum IgG4 level was normal. Although a biopsy specimen was not obtained, the patient was diagnosed with retroperitoneal fibrosis. The patient was treated with steroids. Case 2 involved a 64-year-old man with pulmonary large cell carcinoma. An analysis of the cancer cells revealed that 50-74% of the cells were positive for PD-L1. Lower back pain appeared after one year and 11 months of pembrolizumab treatment. Computed tomography revealed right hydronephrosis and homogeneous plaque on the right side of the abdominal aorta. Although a biopsy specimen was not obtained, the patient was diagnosed with retroperitoneal fibrosis. The patient improved once with steroids but relapsed. Conclusion. We hypothesized that the administration of anti-PD-1 antibodies may have affected the onset of retroperitoneal fibrosis.

Background. There have been few reports of limbic encephalitis in patients with cancer. We herein report a case of limbic encephalitis that developed after treatment with immune checkpoint inhibitors for lung cancer and improved after steroid and anticancer drug therapy. Case. A 72-year-old man visited our hospital complaining of hoarseness. Chest computed tomography (CT) showed a left hilar mass, and a transbronchial lung biopsy of the mass revealed an undifferentiated carcinoma. He was diagnosed with stage IVB non-small-cell lung cancer and treated with anticancer drugs, including pembrolizumab, from November of year X−3 to August of year X−1. Since the therapeutic effect was evaluated as a partial response, he was followed closely without treatment thereafter. At the end of January of year X, amnesic symptoms appeared, and head magnetic resonance imaging showed a high signal in both temporal lobes, leading to a diagnosis of limbic encephalitis. This encephalitis was considered a complication of treatment, being either paraneoplastic neurological syndrome (PNS) or an immune-related adverse events, so steroids were administered. Consequently, his symptoms were alleviated. On chest CT, new mediastinal lymph node enlargement (#4R) was observed, so endobronchial ultrasound-guided transbronchial needle aspiration was performed. The biopsy specimen revealed the histology of the tumor to be so undifferentiated. However, its resemblance to the histology of the primary tumor led to a diagnosis of metastasis. Chemotherapy was started as second-line treatment and resulted in further improvement of the neurological symptoms. Conclusion. Symptoms of PNS often precede the diagnosis of cancer, and the response to steroid treatment is considered poor. Since the delayed onset of neurological symptoms and the presence of a response to steroids in this case were not typical of PNS, we suspect that pembrolizumab influenced the development of limbic encephalitis.