Etoposide soft capsule combined with anlotinib in the third-line treatment of advanced non-small cell lung cancer: a retrospective cohort study.

Background: The physical tolerance in the advanced non-small cell lung cancer (NSCLC) patient often deteriorates, with a limited effective rate of the third-line treatment. This study retrospectively analyzed the efficacy and safety of etoposide soft capsules combined with anlotinib in the third-line treatment of advanced NSCLC. Methods: A retrospective study was conducted on 46 patients with advanced NSCLC who had failed second-line treatment. Progression-free survival (PFS) of advanced NSCLC patients served as an endpoint. Kaplan-Meier survival curves were applied to evaluate the short-term efficacy of anlotinib treatment in advanced NSCLC patients. Results: Among 46 third-line NSCLC patients, none had complete remission (CR), 9 had partial remission (PR), 29 had stable disease (SD), and 8 had progressive disease (PD). The objective response rate (ORR) was 19.57%, the disease control rate (DCR) was 82.61%, the median progression-free survival (mPFS) was 6.3 months, and the median overall survival (mOS) was 10.1 months. Common adverse reactions included fatigue, hypertension, nausea, stomatitis, leukopenia, hand-foot syndrome, abnormal liver function, proteinuria, hemoptysis, and hypothyroidism, among others. The incidence of grade 3 adverse reactions was 8.9%, and there were no grade 4 adverse reactions. Conclusions: Etoposide soft capsule combined with anlotinib demonstrated a marked effect on the third-line treatment of advanced NSCLC patients, and is well tolerated.

Preoperative state anxiety predicts postoperative health-related quality of life: A prospective observational study on patients undergoing lung cancer surgery.

Objective: Improving quality of life (QOL) after surgery is very important. Recently, preoperative anxiety has been suggested to predict postoperative health-related (HR) QOL, however the accuracy of anxiety measurement remains problematic. We examined the relationship between preoperative anxiety level and postoperative HRQOL using qualitative and quantitative assessment of anxiety. Method: We used a detailed anxiety assessment to quantitatively investigate preoperative anxiety as a predictor of postoperative HRQOL in lung cancer patients. Fifty one patients who underwent surgery for lung cancer were included. They were assessed four times: on admission, on discharge, 1 month after surgery, and 3 months after surgery. Anxiety was measured separately as "state anxiety" and "trait anxiety" using the State-Trait Anxiety Inventory, and HRQOL was measured using the EuroQol 5 dimension 5-level. Results: The HRQOL decreased at discharge and gradually recovered over time, reaching the same level at 3 months after surgery as at admission. HRQOL score was lower at discharge than at pre-surgery and 3 months after the surgery (p < 0.0001 each), and the score at 1 month after the surgery was lower than at pre-surgery (p = 0.007). In addition, multiple regression analysis showed that HRQOL at discharge was associated with "state anxiety" rather than "trait anxiety" at admission (p = 0.004). Conclusion: This study identifies the types of anxiety that affect postoperative HRQOL. We suggest that postoperative HRQOL on discharge may be improved by interventions such as psychological or medication treatment for preoperative state anxiety if identified preoperative state anxiety can be managed appropriately.

Efficacy and safety of anlotinib combined with carboplatin and pemetrexed as first-line induction therapy followed by anlotinib plus pemetrexed as maintenance therapy in EGFR/ALK wild-type advanced non-squamous non-small cell lung cancer in China: a multicenter, single-arm trial.

Background: The efficacy and safety of chemotherapy strategies combining the multi-target receptor tyrosine kinase inhibitor in patients with advanced EGFR/ALK wild-type non-squamous non-small-cell lung cancer (nsq-NSCLC) are undetermined. We aimed to investigate the efficacy and safety of anlotinib combined with carboplatin/pemetrexed-based chemotherapy followed by maintenance therapy (anlotinib plus pemetrexed) in advanced EGFR/ALK wild-type nsq-NSCLC. Methods: Eligible patients with wild-type EGFR/ALK advanced nsq-NSCLC who received first-line therapy in Henan Province from March 2019 to February 2021 were recruited. All patients were treated with anlotinib in combination with carboplatin/pemetrexed-based chemotherapy, followed by maintenance therapy (anlotinib plus pemetrexed). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs). Response and AEs were assessed based on the Response Evaluation Criteria in Solid Tumors (1.1) and National Cancer Institute - Common Terminology Criteria for Adverse Events v.4.0.3, respectively. The follow-up interval for survival was 6 weeks and the safety follow-up was performed until the end of treatment. Kaplan-Meier analysis was used to calculate the median PFS and OS. Results: Thirty-eight participants with median age of 62 (range, 33-75) years were evaluated. Five participants were still on maintenance therapy until the end of the study. The majority were non-smokers (68.4%). The median follow-up was 13.6 (range, 12.3-14.9) months. The median PFS (mPFS) was 10.5 (95% CI: 4.1, 17.0) months, and the median OS was 23.4 [95% CI: not evaluable (NE), NE] months. The DCR and ORR were 94.7% and 60.5%, respectively. Grade 3 and above treatment-related adverse events (TRAEs) happened to 12 participants. The most common TRAEs were hypertension (23.7%), neutropenia (19.4%), and bone marrow toxicity (10.5%). Seven patients discontinued treatment, including two patients during induction and five patients during maintenance treatment. No grade 5 TRAE was reported. In the non-smoker participants, the mPFS was 14.5 (95% CI: 4.0-25.0) months. Conclusions: Anlotinib in combination with carboplatin/pemetrexed-based chemotherapy followed by anlotinib plus pemetrexed as maintenance therapy might be an effective choice in treating patients with wild-type EGFR/ALK advanced nsq-NSCLC.

Impact of the first surge of the coronavirus disease pandemic on general thoracic surgery practices in Kanagawa: a questionnaire survey by the Kanagawa General Thoracic Surgical Study Group.

OBJECTIVES: The first surge in severe acute respiratory syndrome coronavirus 2 infection had a significant impact on health care institutions. Understanding how the pandemic affected general thoracic surgery would provide valuable data for establishing a health care protocol for upcoming surges. METHODS: A questionnaire survey on coronavirus disease-related patient statistics and health care was conducted between February 2020 and June 2020 across 14 facilities affiliated with the Kanagawa General Thoracic Surgery Study Group. RESULTS: The average number of newly referred patients from February to June 2020 was 65% of that during the same period in 2019. Six facilities placed restrictions on medical care services, among which four restricted surgeries. At all institutions and those placed on surgical restriction, the total number of surgeries under general anesthesia was 92% and 78%, the total number of primary lung cancers was 94% and 86%, and the total number of surgeries for pneumothorax was 71% and 77% of that in the preceding year, respectively. Infection control and insufficient resources of the medical material were the most influential factors impacting the medical institutions' decision to restrict the services provided. CONCLUSIONS: Restrictions on surgery had a significant impact on the care provided by general thoracic surgery departments. To avoid patient inconvenience, establishing a collaborative system that refers patients to operational medical institutions in case of medical treatment restrictions may be useful.

A case of epithelioid cell granulomas arising at the margin of lung resection, with high accumulation on 18F-fluorodeoxyglucose-positron emission tomography.

It is important to distinguish tumour recurrence from other conditions that could show high accumulation on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). We describe the case of a 78-year-old woman who underwent partial resection of the left lower lung lobe for carcinoid treatment 20 years previously. Five years earlier, chest radiography revealed an abnormal shadow, and chest computed tomography (CT) showed partial atelectasis in the left S8. Periodical CT showed that the atelectasis had developed into a mass. The patient was referred to our hospital. A mass of 45 mm diameter was detected on CT and it had a maximum standardized uptake value of 8.91 on FDG-PET. We suspected recurrence and performed surgery. Pathological examination revealed epithelioid cell granuloma (maximum diameter, 25 mm) with necrosis. Tissue culture showed no evidence of Mycobacterium tuberculosis. However, serum anti-MAC antibody level was elevated, suggesting epithelioid cell granuloma caused by non-tuberculous Mycobacterium infection.

Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial.

BACKGROUND: Although platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC. METHODS: Enrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity (RDI) was 79% for S-1 and 80% for cisplatin. The 2-year DFS rate was 42.1%, and 2-year OS rate was 83.3%. CONCLUSIONS: This study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy. TRIAL REGISTRATION: This study was registered on the UMIN clinical study registration site (protocol ID: UMIN000016191) on December 1, 2015.

The Usefulness of Positron-Emission Tomography Findings in the Management of Anterior Mediastinal Tumors.

PURPOSE: We performed a retrospective analysis to evaluate the usefulness of positron-emission tomography/computed tomography (PET/CT) findings in the classification and management of anterior mediastinal tumors. METHODS: Between 2006 and 2015, 105 patients with anterior mediastinal tumor received PET/CT. 18F-fluorodeoxyglucose (18F-FDG)-PET images were obtained 60 minutes after the injection of 18F-FDG. RESULTS: The histological classifications were as follows: thymoma (n = 49), thymic carcinoma (TC) (n = 19), malignant lymphoma (ML) (n = 8), teratoma (n = 7), thymic cyst (n = 14), and others (n = 8). Upon visual inspection (SUV max: >2.0), all of the malignant tumors showed 18F-FDG accumulation (with the exception of one type A thymoma). Two of the 14 thymic cysts and three of the seven teratomas showed slight 18F-FDG accumulation. The SUV max values of the low-grade thymomas, high-grade thymomas, TCs and MLs were 3.14 ± 0.73, 4.34 ± 1.49, 8.59 ± 3.05, and 10.08 ± 2.53, respectively, with significant differences between the low- and high-grade thymomas, and between TCs and MLs. The sensitivity, specificity and accuracy of 18F-FDG in the detection of low-grade thymomas and thymomas with a maximum diameter of ≤50 mm and an SUV max of ≤3.4 were 85%, 48%, and 60%, respectively. CONCLUSION: FDG-PET/CT is an objective and useful modality in the differential diagnosis and management of anterior mediastinal tumors.

Expression of PTEN and its pseudogene PTENP1, and promoter methylation of PTEN in non-tumourous thymus and thymic tumours.

AIMS: Mutation or promoter methylation of the phosphatase tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN) promotes some cancers. Moreover, PTENP1 (PTEN pseudogene) transcript regulates PTEN expression and is thought to be associated with tumourigenesis in some cancers. Here, we investigated PTEN expression in thymic epithelium and thymic epithelial tumours. METHODS: Immunohistochemical analysis of PTEN was performed on two non-tumourous thymus (NT) samples, 33 thymomas (three type A, eight type AB, 11 type B1, six type B2, and five type B3), and four thymic carcinomas (TCs). In 16 cases (two NT, three A, five B1, two B2, one B3 and three TC), analyses of mutations, promoter methylation and comparisons of PTEN mRNA and PTENP1 transcripts were undertaken using PCR-direct sequencing, methylation-specific PCR, and reverse-transcription real-time PCR after target cell collection with laser microdissection. RESULTS: PTEN protein was not immunohistochemically detected in NT epithelium or types B1 or B2 thymoma cells, but was expressed in type A thymoma and carcinoma cells. Neither PTEN mutations nor promoter methylation were detected in any samples. Statistical analysis revealed that PTEN mRNA expression was highest in NT epithelium and lowest in type A thymoma cells. PTENP1 transcript expression did not significantly differ among NT, thymoma and TC samples. CONCLUSIONS: We speculated that NT epithelium and types B1/B2 thymoma cells have a mechanism of PTEN translation repression and/or acceleration of protein degradation, whereas type A thymoma cells exhibit transcriptional repression of PTEN mRNA and accelerated translation and/or protein accumulation.

Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic Events.

Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder caused by genetic mutations in the folliculin (FLCN) gene. Individuals with BHD have multiple pulmonary cysts and are at a high risk for developing renal cell carcinomas (RCCs). Currently, little information is available about whether pulmonary cysts are absolutely benign or if the lungs are at an increased risk for developing neoplasms. Herein, we describe 14 pulmonary neoplastic lesions in 7 patients with BHD. All patients were confirmed to have germline FLCN mutations. Neoplasm histologies included adenocarcinoma in situ (n = 2), minimally invasive adenocarcinoma (n = 1), papillary adenocarcinoma (n = 1), micropapillary adenocarcinoma (n = 1), atypical adenomatous hyperplasia (n = 8), and micronodular pneumocyte hyperplasia (MPH)-like lesion (n = 1). Five of the six adenocarcinoma/MPH-like lesions (83.3%) demonstrated a loss of heterozygosity (LOH) of FLCN. All of these lesions lacked mutant alleles and preserved wild-type alleles. Three invasive adenocarcinomas possessed additional somatic events: 2 had a somatic mutation in the epidermal growth factor receptor gene (EGFR) and another had a somatic mutation in KRAS. Immunohistochemical analysis revealed that most of the lesions were immunostained for phospho-mammalian target of rapamycin (p-mTOR) and phospho-S6. Collective data indicated that pulmonary neoplasms of peripheral adenocarcinomatous lineage in BHD patients frequently exhibit LOH of FLCN with mTOR pathway signaling. Additional driver gene mutations were detected only in invasive cases, suggesting that FLCN LOH may be an underlying abnormality that cooperates with major driver gene mutations in the progression of pulmonary adenocarcinomas in BHD patients.

Correlation between histological invasiveness and the computed tomography value in pure ground-glass nodules.

PURPOSE: The purpose of this study was to evaluate the correlation between histological invasiveness and the computed tomography (CT) value and size in pure ground-glass nodules (GGNs) to determine optimal "follow-up or resection" strategies. METHODS: Between 2001 and 2014, 78 resected, pure GGNs were retrospectively evaluated. The maximum diameter and CT value of pure GGNs were measured using a computer graphics support system. RESULTS: All GGNs with a maximum diameter ≤10 mm and CT value ≤-600 Hounsfield units (HU) were considered to be noninvasive lesions, while 21 of 26 (81 %) with a maximum diameter >10 mm and CT value >-600 HU were considered to be invasive lesions. With respect to the correlation between each histological type and pure GGN with a maximum diameter ≤10 mm and CT value ≤-600 HU, the specificity was 90 % and the sensitivity and negative predictive value were both 100 % in atypical adenomatous hyperplasia (AAH), while the specificity was 58 % and the sensitivity and positive predictive value were 0 % in minimally invasive and invasive adenocarcinoma. CONCLUSION: Pure GGNs with a maximum diameter of ≤10 mm and CT value of ≤-600 HU are nearly always pre-invasive lesions; therefore, surgery should be carefully selected in such patients.

A Surgical Case of Bronchial Artery Aneurysm Directory Connecting with Pulmonary Artery.

We present a surgical case of bronchial artery aneurysm (BAA) connecting pulmonary artery accompanied with racemose hemangioma. This is a third surgical case report of BAA directly connecting pulmonary artery in the English literature. A 63-year-old female was found a BAA, 2 cm in diameter, connecting right A4 pulmonary artery. The patient underwent two attempts for embolization. However, due to extensive collaterals, there was persistent flow in the aneurysm. Standard lateral thoracotomy was performed. A BAA was located between A4 and A5 PA. A small branch of A4 PA was separated, and the small vessel connecting to the BAA could be ligated. A5 PA was separated similarly, however BAA was ruptured not to identify the other small vessel connecting to the BAA. After a clamp of the BAA, middle lobe lobectomy was performed. We removed the aneurysm with dilated bronchial artery connecting to the aneurysm. The postoperative course was uneventful.

One-dimensional mean computed tomography value evaluation of ground-glass opacity on high-resolution images.

OBJECTIVE: Differentiation of atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and invasive carcinoma on computed tomography (CT) is useful for determining "follow-up or resection" strategies for lesions displaying ground-glass opacity (GGO). The purpose of this study is to evaluate one-dimensional quantitative CT values of GGO on high-resolution CT (HRCT) images using computer-aided diagnosis. METHODS: Between April 2001 and March 2010, a total of 44 nodules in 42 patients with pure or mixed GGOs ≤2 cm were retrospectively evaluated. Maximum diameter and one-dimensional mean CT (m-CT) value of the diameter were measured using a computer graphics support system (HOPE/DrABLE-EX, Fujitsu, Tokyo, Japan) that displays a CT density profile across the tumor. RESULTS: m-CT values were -682 ± 64 HU (range) for AAH lesions, -544 ± 179 (range) for Type A lesions, -496 ± 147 (range) for Type B lesions, and -371 ± 142 (range) for invasive lesions. AAH lesions had a significantly lower m-CT value than Type B lesions. AAH, Type A, and Type B lesions had significantly lower m-CT values than invasive lesions (p < 0.05). All seven GGO lesions with a maximum diameter ≤1 cm and m-CT value ≤-600 HU were pre-invasive lesions, while 16 of 22 (73 %) cases with maximum diameter >1 cm and m-CT value >-600 HU were invasive lesions. CONCLUSION: Observation may be indicated for GGO lesions with a maximum diameter ≤1 cm and m-CT value ≤-600 HU.

Radical resection of a pleomorphic carcinoma after relieving airway obstruction by the endobronchial snare method.

A 69-year-old man was hospitalized for fever and cough. He was diagnosed with and treated for an abscess in the left lower jaw and pneumonia by an otolaryngologist, but the pneumonia persisted with no improvement. Chest computed tomography revealed the presence of a heterogeneous torose lesion in the inlet of the left upper bronchus, and bronchoscopy revealed an endobronchial tumor with a smooth surface. An episode of sudden dyspnea occurred and was resolved after the patient changed his sitting position. We concluded that this symptom occurred because the tumor was incarcerated in the left lower lobe bronchus. The tumor was excised by bronchofi berscopic snare resection under tracheal intubation. It was found to be a pleomorphic carcinoma, and left upper lobectomy was performed. There has been no recurrence during the 3 years since the operation.

Thymoma with intracystic dissemination arising in a unilocular thymic cyst.

A 33-year-old asymptomatic woman was referred to our hospital for evaluation of an abnormal shadow on a chest radiograph. A chest-computed tomogram revealed a cystic, partially solid tumor in the right inferior mediastinum. Following an initial diagnosis of cystic teratoma, surgery was performed. The tumor, a well-encapsulated, thin-walled cyst located within the right inferior lobe of the thymus, was extirpated by partial resection of the thymus. The cut surface revealed a unilocular cyst containing multiple grayish-white tumors on the inner cyst walls. Some tumors detached from the wall owing to loose connections. Microscopic findings revealed that the cyst was lined with squamous epithelium. The tumor on the cyst wall was diagnosed to be a type B1 thymoma. Based on these findings, we diagnosed this case as a thymoma originating from the wall of a thymic cyst, accompanied by intracystic dissemination from the tumor.