[Tracheobronchial Foreign Body].

Foreign body aspiration is most common in infants of <3 years of age and the elderly. Peanuts and plant seeds account for approximately 70~80% of airway foreign bodies in children, while dental materials( e.g., dentures and crowns) are common in adults. Tracheobronchial foreign bodies are diagnosed by detailed history taking, careful auscultation, chest radiography, and computed tomography (CT). Chest radiography should be performed in frontal and lateral views. CT is useful for assessing the presence of a foreign body, the site of involvement, and secondary changes (e.g., pneumonia or atelectasis). In urgent cases with severe dyspnea, life-saving measures, including endotracheal intubation, administration of oxygen, and securing an intravenous line should be performed first, followed by immediate removal. Removal is often performed with a rigid bronchoscope in children, and a flexible bronchoscope under local anesthesia in adults. When removal by flexible bronchoscope is difficult, a rigid bronchoscope is used. Surgical removal is considered when bronchoscopic removal is difficult or associated with a high risk of complications( e.g., major bleeding or bronchial perforation). After removal, pneumonia is likely to occur, so antibiotic agents should be administered. For airway foreign bodies, appropriate and immediate treatment is required from the diagnosis to removal and post-removal management.

[Reoperation for Secondary Cancer Following the Excision of Pulmonary Cancer].

There has been an increase in cases in which complete recovery is possible through surgery thanks to improvements in multimodal therapy along with increased early-stage pulmonary cancer in conjunction with the spread of pulmonary cancer computed tomography (CT) examinations and advancements in image diagnostic technologies. Moreover, post-operative follow-ups are now conducted for a relatively longer period of time, so there are now more opportunities to treat secondary cancer. It is difficult to determine if nodules that occur following pulmonary cancer surgery are cases of secondary cancer or cases of relapse. In the case of a solitary nodule, it cannot be assumed that there has been a complete recovery from cancer, so reoperation should be actively considered. In the event of reoperation, not only should the expected post-operative pulmonary function be considered, but whether the location is the same lung or the other lung, the blood flow distribution of the remaining lung, as well as other factors, should also be considered. Reoperation on the same lung is extremely difficult because it assumes a high degree of accretion in the cavum thoracis. Even if reduction surgery or lobectomy of the remaining lung is planned, separation is difficult, with potential unforeseen conditions such as hemorrhaging. Therefore, this assumes unavoidable total extirpation of the remaining lung. Regarding reoperation on the other lung, attention must be paid to management of the respiratory system during surgery. Further, blood circulation relies on the lung in which the reoperation is to be performed more than expected, with cases existing in which complications such as pulmonary edema may occur due to a rapid reduction of the pulmonary vascular bed as a result of a pulmonary resection. In particular, attention must be paid to respiratory failure and heart failure in the event of a lobectomy in both lungs. Prior to surgery, it is beneficial to evaluate the blood distribution with a pulmonary blood flow scintigram. As suggested above, reoperation on secondary cancer following pulmonary cancer excision requires a detailed treatment plan before the operation.

[Surgical Treatment and Outcomes for Synchronous Multiple Lung Cancer].

OBJECTIVES: With the advent of high-resolution chest imaging systems and lung cancer screening programs, the number of patients diagnosed with multiple primary lung cancers is increasing. For the treatment of multiple lung cancers, a surgical procedure that preserves the lung function while ensuring curability is required. We herein report the surgical strategy and outcomes of synchronous multiple lung cancer. SUBJECTS: The subjects were 83 patients with synchronous multiple lung cancer who received surgical resection between January 2010 and March 2020. Cases within the same lobe were excluded, and only cases with two or more lobes involved were included in this study. RESULTS: The study enrolled 39 male and 44 female patients, and the mean age was 67.8 years old. Sixty-five patients had cancers within a unilateral lobe, and all had undergone surgery for one term. Eighteen patients had cancers in bilateral lobes, and 17 of them received secondary surgery for more advanced cancer. Bilobectomy was performed in 9 patients( 10.8%), consisting of 5 upper-middle lobectomies, 3 middle-lower lobectomies, and 1 right middle lobectomy with left lower lobectomy. Seventy-four patients (89.2%) underwent combination surgery with sublobar resection, such as segmentectomy and partial resection. Pneumonectomy was not performed in any patients. The histologic type was adenocarcinoma in 78 patients (94.0%), and 37 patients (47.4%) had adenocarcinoma in situ. Regarding the most advanced pathological stage, 57 patients( 68.7%) were stage≤Ⅰ, and 26( 31.3%) were stage≥Ⅱ. Postoperative complications were observed in 29 patients( 34.9%), and persistent pulmonary fistula of ≥7 days after the surgery was the most common, being observed in 16 patients. Operative death within 30 days after surgery occurred in 2 patients( 2.4%)[ due to pneumonia in 1 and cerebral infarction in 1]. None of the patients required home oxygen therapy after surgery. Recurrence occurred in 20 patients;14 of these had pathological stage ≥Ⅱ, 11 had lymph node metastases, and 2 had pleural dissemination. The recurrence patterns were metastasis to other organs, pleural dissemination, or lymph node metastasis;no local recurrence was observed. The mean recurrence-free survival was 32.4 months, and the five-year survival rate was 84.8%. On comparing outcomes according to the most advanced pathological stage, the five-year survival rate for stage ≤Ⅰdisease was 94.9%, and that for stage ≥Ⅱ disease was 61.7%, showing a significantly better prognosis for stage ≤Ⅰdisease (p<0.001). CONCLUSIONS: Selecting an appropriate operative procedure for synchronous multiple lung cancer renders the prognosis equivalent to that of single cancer. Surgical treatments, including sublobar resection, are thus deemed important.

Urinary metabolites identified using metabolomic analysis as potential biomarkers of nocturia in elderly men.

PURPOSE: To investigate the association between nocturia and urinary metabolites in elderly men using metabolomic analysis. METHODS: We recruited 66 men aged 65-80 years. The 3-day frequency volume chart (FCV), International Prostate Symptom Score (IPSS), and quality of life score were used to assess micturition behavior. Participants with the total IPSS > 0 and ≥ 1.5 micturition on an average for three nights were included in the nocturia group. Participants with the total IPSS < 8 and < 1.5 micturition at night were included in the control group. We conducted a comprehensive metabolomic analysis of urine samples. Metabolites were compared between the groups using an unpaired t test. A multivariable logistic regression analysis was used to determine the relationship between nocturia and these metabolites. RESULTS: The nocturia and control groups consisted of 45 and 21 men, respectively. There were no differences in the background factors between the groups except for receiving anticholinergic drug and having life style-related diseases. The FVC revealed that nocturnal urine volume, 24 h micturition frequency, and nocturnal micturition frequency were significantly higher in the nocturia group than in the control group. The metabolomic analysis revealed 16 metabolites, which were differentially expressed between the groups. The multivariate analysis showed that increased serotonin level and decreased 3-hydroxypropionic acid and 3-indoleacetonitrile levels were associated with nocturia. CONCLUSIONS: These findings suggest that abnormal urinary metabolites including serotonin, 3-hydroxypropionic acid, and 3-indoleacetonitrile are involved in the pathogenesis of nocturia in elderly men.

Liquid chromatography-mass spectrometry identification of serum biomarkers for nocturia in aged men.

PURPOSE: We aimed to investigate the association between nocturia and serum metabolites identified using metabolomics analysis. METHODS: This study enrolled 66 men aged 65-80 years, recruited from the outpatient department of a university hospital. The participants were stratified as follows: Nocturia group [45 men with any total international prostate symptom score (IPSS) and an average of 3 nights ≥ 1.5 micturitions/night] and Control group (21 men with total IPSS < 8 and an average of 3 nights < 1.5 micturitions/night). The 24-h frequency-volume chart, IPSS, and Quality-of-Life questionnaire were used to evaluate micturition behavior. Serum metabolite profiles were obtained using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics analysis and compared between the two groups using the unpaired t test. The relationship between serum metabolites and nocturia was determined using multivariable logistic regression analysis. RESULTS: There were no differences in background factors between the Nocturia and Control groups. In the IPSS, mean total scores in the Nocturia and Control groups were 12.4 and 4.0, respectively. On frequency-volume chart analysis, nocturnal urine volume and micturition frequency during daytime and nighttime were significantly higher in the Nocturia group. LC-MS highlighted 13 serum metabolites as potential biomarkers of nocturia. On multivariate analysis, increased levels of palmitoylethanolamide, 4-hydroxydocosahexaenoic acid, 9-hydroxyoctadecadienoic acid, 20-hydroxydocosahexaenoic acid, 13-hydroxyoctadecadienoic acid, arachidonoylethanolamide, eicosapentaenoic acid, 12-hydroxy-eicosatetraenoic acid, and arachidonic acid were associated with nocturia. CONCLUSIONS: In aged men, the pathogenesis of nocturia involves abnormal metabolism in several signaling pathways involving omega-3 and omega-6 polyunsaturated fatty acids, as well as endocannabinoids.

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

BACKGROUND: The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. MATERIAL AND METHODS: Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. RESULTS: Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. CONCLUSIONS: SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Distinct prognostic roles and heterogeneity of TTF1 copy number and TTF1 protein expression in non-small cell lung cancer.

Thyroid transcription factor 1 (TTF1) located on chromosome band 14q13.3 is an oncogene and a suppressor gene in non-small cell lung cancer (NSCLC). The prognostic relevance of TTF1 copy number alterations (CNAs) and their association with TTF1 protein expression are poorly understood. Here, we assessed TTF1 CNAs and protein expression using microarrays in a cohort of 636 NSCLC, including 423 adenocarcinoma (ADC) and 171 squamous cell carcinoma (SCC). In addition, fluorescent in situ hybridization and immunohistochemistry were performed. TTF1 CNAs were detected in 23% of NSCLC (23% of ADC and 20% of SCC). Specifically, TTF1 amplification and polysomy were observed in 5% and 18% of NSCLC, and in 7% and 16% of ADC, respectively. TTF1 expression was detected in 85% of ADC. TTF1 CNAs were significantly associated with advanced tumor stage, EGFR mutations, and TTF1 expression. A multivariate Cox hazards model analysis of overall survival and recurrence-free survival demonstrated that both TTF1 amplification and polysomy were independent indicators of an unfavorable prognosis in patients with NSCLC. Survival was inversely correlated with TTF1 copy number. In contrast, TTF1 protein expression was an independent favorable prognostic factor. Intratumoral and intertumoral heterogeneities of TTF1 CNAs and TTF1 protein expression were assessed using primary cores from 138 pairs of primary tumors and corresponding nodal metastases. The concordance rate for TTF1 CNAs and TTF1 protein expression was high within tumors and between primary and metastatic tumors. Altogether, these results suggest that TTF1 CNAs are correlated with TTF1 protein expression, but have opposing effects on survival.

[Outcome of Surgical Treatment of Locally Advanced Lung Cancer after Induction Chemoradiotherapy].

OBJECTIVE: The outcome of surgical treatment of non-small-cell lung cancer after induction chemoradiotherapy was investigated. SUBJECTS: The subjects were 74 patients with non-small-cell lung cancer who received induction chemoradiotherapy( ICRT) between 1998 and 2016. ICRT was administered to pT3 lung cancer invading the chest wall(20 patients), pT4 lung cancer invading the adjacent organ(22 patients), and cN2 lung cancer(32 patients). cN2 was confirmed by mediastinoscopy(13 patients) and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)(19 patients). RESULTS: Sixty-eight and 6 patients were male and female, respectively, and the mean age was 59.6 years old. The histologic type was adenocarcinoma in 43 patients, squamous cell carcinoma in 24, adenosquamous carcinoma in 5, and others in 2. In chemotherapy, 2 or more anticancer drugs including platinum agent were administered. The radiation dosage was 36 Gy in 1 patient, 40 Gy in 43, 50 Gy in 28, and 60 Gy in 2. The effect of ICRT was complete response( CR) in 1 patient, partial response( PR) in 40, and stable disease (SD) in 33 (CR+PR:55.4%). The surgical procedure was lobectomy in 60 patients, pneumonectomy in 10, bilobectomy in 3, and segmentectomy in 1. Tracheobronchoplasty was performed in 9 patients, and combined resection of the vertebral body, left atrium, carina, superior vena cava, aorta, and brachiocephalic subclavian artery was performed in 7, 5, 4, 3, 3, and 3 patients, respectively. Regarding postoperative complications, empyema developed in 5 patients, acute respiratory distress syndrome(ARDS)in 3, pneumonia in 3, tracheobronchial dehiscence in 2, postoperative hemorrhage in 1, atrial fibrillation in 1, and others in 5. Postoperative complication rate was 27.0%, and operative death occurred due to postoperative hemorrhage in 1 patient. Complete resection was achieved in 69 patients(93.2%). Regarding the histological effect of ICRT, Ef.1/2/3 = 32/28/14(Ef.2-3:56.7%), and down stage was achieved in 24 patients (32.4%). The 5-year survival rate of all 74 patients was 51.0%, median survival time (MST)was 62.7 months, and the recurrence-free survival rate was 47.3%. Recurrence occurred in 28 patients (40.6%)with complete resection and the recurrence was distant metastasis in 20 of them. Regarding the outcome by the effect of ICRT, the 5-year survival rates of patients who achieved CR+PR/SD, Ef.2-3/Ef.0-1, and down stage/non-down stage were 66.0%/34.3%(p=0.009), 73.2%/20.1%(p=0.001), and 83.7%/44.0%(p=0.02), respectively, showing that the outcomes of patients who achieved CR/PR, Ef.2-3, and down stage were significantly favorable. CONCLUSION: The morbidity and mortality rates of patients who underwent surgery after ICRT were 27 and 1.4%, respectively. More than half of the patients achieved CR-PR and Ef.2-3, 1/3 of the cases were down staged, and the outcomes of these patients were significantly favorable. Surgery after ICRT may improve the treatment outcome of patients with locally advanced lung cancer.

Characterization of V-set and immunoglobulin domain containing 1 exerting a tumor suppressor function in gastric, lung, and esophageal cancer cells.

V-set and immunoglobulin domain containing 1 (VSIG1) is a newly discovered member of the immunoglobulin superfamily of proteins, expressed in normal stomach and testis. In cancers, however, the clinical and biological roles of VSIG1 remain unknown. Here we investigated VSIG1 expression in 11 cancers and assessed the prognostic roles of VSIG1 in patients with gastric cancer (GC) (n = 362) and non-small-cell lung cancer (n = 650). V-set and immunoglobulin domain containing 1 was downregulated in 60.5% of GC specimens, and high VSIG1 expression was identified as an independent favorable prognostic factor for overall survival in GC patients (hazard ratio, 0.58; 95% confidence interval, 0.35-0.96). Among lung adenocarcinomas (n = 428), VSIG1 was significantly and inversely associated with thyroid transcription factor 1 expression and was frequently expressed in the invasive mucinous subtype (17 of 19, 89.5%). In addition, VSIG1 was expressed in a subset of pancreatic, ovarian, and prostate cancers. The variant 2 VSIG1 transcript was the dominant form in these tissues and cancer cells. Introduction of VSIG1 significantly reduced the proliferative ability of MKN1 and MKN28 GC cells and H1299 lung cancer cells and downregulated cell migration of these cells, as well as of KYSE150, an esophageal cancer cell line. Cell invasion of MKN1, MKN28, and KYSE150 cells was also reduced by VSIG1 introduction. In vitro characterization revealed that VSIG1 forms homodimers through homophilic cis-interactions but not through homophilic trans-interactions. These results suggest that VSIG1 possesses tumor suppressive functions that are translated into favorable prognosis of VSIG1-expressing GC patients.

WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma.

Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test). An immunohistochemical analysis for LAC (n = 237) showed that WDR62 proteins were also significantly overexpressed in LAC (P < 0.0001, Mann-Whitney U test). A Kaplan-Meier analysis demonstrated that patients with LAC who exhibit WDR62 overexpression have a short overall survival (P = 0.0378, log-rank test), and a multivariate analysis revealed that WDR62 overexpression was an independent predictor of a poor survival outcome among LAC patients (hazard ratio, 2.032; 95% confidence interval, 1.071-3.777; P = 0.0305). Next, we examined the functional effect of WDR62 overexpression on the lung cancer cell line H1299. WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification in the lung cells. Finally, we disclosed that the concurrent overexpression of WDR62 and TPX2 is common in diverse human cancers, using data from the Cancer Genome Atlas. These results suggested that WDR62 overexpression is associated with a poor prognosis in patients with LAC and leads to an increase in the malignant potential of lung cells.

A Phase II Study of Partial and Subtotal Thymectomy for Thymoma (JART02).

BACKGROUND: We believe the merit of preservation of a part of the thymus following surgery for thymoma. We evaluated the efficacy of partial or subtotal thymectomy for early-stage thymoma in the prospective study. METHODS: The Japanese Association for Research on the Thymus conducted a multiple institutional study of thymectomy for thymoma localized in the thymus without total thymectomy. Patients without autoimmune disease who had an anterior mediastinal tumor that had been clinically diagnosed as an early-stage thymoma were enrolled in the study. Patients who were positive for anti-acetylcholine receptor antibodies were excluded. RESULTS: Sixty-three patients were enrolled preoperatively; 27 patients were judged as being inappropriate based on the other thymic pathologies or tumor invasion. The remaining 36 cases were diagnosed as early-staged thymoma and analyzed. The mean age of the patients was 61 years. The mean maximal tumor diameter in the resected specimens was 3.6 cm. The most common pathological types of thymoma were AB (n = 10) and B1 (n = 10). The Masaoka stages were classified as stage I (n = 22) and II (n = 14). The mean observation period was 63 months. Two patients died due to respiratory dysfunction, which was not related to thymoma. One hundred percent of the patients remained recurrence-free. CONCLUSIONS: This prospective study suggested the efficacy of partial or subtotal thymectomy for early-stage thymoma in patients without any apparent evidence of autoimmune disease. We can preserve a part of the thymus even following surgery for thymoma to prepare the possible second malignancies or diseases in future.

The Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology.

OBJECTIVE: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology. METHODS: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone. RESULTS: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %). CONCLUSION: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.

[A Patient with Lung Adenocarcinoma, Lymphangitis Carcinomatosa, and Multiple Bone Metastases Who Achieved Long-Term Survival after Successful Treatment with Carboplatin, Paclitaxel, and Bevacizumab].

BACKGROUND: Lymphangitis carcinomatosa of the lung is intractable and associated with a poor prognosis. CASE: A 53-year-old woman was admitted to our hospital due to an uncomfortable feeling on deep inspiration. She was diagnosed with left lung adenocarcinoma with lymphangitis carcinomatosa and bone metastases to the frontal bone of the skull and thoracic vertebrae. The lung carcinoma was positive for an EGFR mutation. Because the patient's performance status (PS) was 0, carboplatin plus paclitaxel plus bevacizumab therapy was initiated and she received zoledronic acid and concurrent radiation therapy of 40 Gy for the metastasis to the thoracic vertebrae. After 2 courses of treatment, the respiratory symptoms had improved. After 6 courses of treatment, a chest CT indicated that the lymphangitis carcinomatosa had disappeared. The serum CEA level, which was 126.2 ng/mL (normal<5.0) before treatment, reduced to 5.0 ng/mL. She was administered 10 courses of bevacizumab as a maintenance therapy; however, the CEA level rose again to 11.7 ng/mL, the lung tumor volume increased, and the metastasis of the frontal bone deteriorated. As second-line chemotherapy, EGFR-TKI was started. However, after 11 months, because of grade 4 liver dysfunction, EGFR-TKI was stopped. She then received fourth-line chemotherapy in our outpatient hospital. This patient has survived 52 months since the initial diagnosis. CONCLUSION: Chemotherapy including bevacizumab facilitated long-term survival (52 months) of a patient with lung adenocarcinoma accompanied by lymphangitis carcinomatosa and multiple bone metastases.

[Chest Wall Injury].

The thoracic wall protects the heart, great vessels, lungs, trachea, and bronchus, which are organs important for maintaining respiration/circulation, against external forces. Therefore, injury of the thoracic wall may necessitate emergency treatment. Such injury primarily consists of rib and sternal fractures. In particular, fractures of 2 or more consecutive ribs with each rib being fractured at 2 or more sites and serial rib fracture with sternal fracture lead to reverse thoracic movement involving contraction on inhalation and expansion on expiration. Such thoracic injury is termed flail chest. Injury of the thoracic wall, such as flail chest, markedly influences the prognosis. Therefore, it is necessary to promptly evaluate the general condition, involving respiratory/circulatory kinetics, confirm the presence or absence of concomitant injury, such as bruises of the lungs/heart, and accurately select therapeutic strategies, including artificial respiration and surgical intervention.

RSPO fusion transcripts in colorectal cancer in Japanese population.

R-spondin (RSPO) gene fusions have recently been discovered in a subset of human colorectal cancer (CRC) in the U.S. population; however, whether the fusion is recurrent in CRC arising in patients from the other demographic areas and whether it is specific for CRC remain uncertain. In this study, we examined 75 primary CRCs and 121 primary lung cancers in the Japanese population for EIF3E-RSPO2 and PTPRK-RSPO3 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of EIF3E-RSPO2 and PTPRK-RSPO3 was not detected in any of the lung carcinomas, RSPO fusions were detected in three (4%) of the 75 CRCs. Two CRCs contained EIF3E-RSPO2 fusion transcripts, and another CRC contained PTPRK-RSPO3 fusion transcripts. Interestingly, in one of the two EIF3E-RSPO2 fusion-positive CRCs, a novel fusion variant form of EIF3E-RSPO2 was identified: exon 1 of EIF3E was connected to exon 2 of RSPO2 by a 351-bp insertion. A quantitative RT-PCR analysis revealed that RSPO mRNA expression was upregulated in the three CRCs containing RSPO fusion transcripts, while it was downregulated in nearly all of the other CRCs. An immunohistochemical analysis and a mutational analysis revealed that the RSPO fusion-containing CRC had a CDX2 cell lineage, was positive for mismatch repair protein expression, and had the wild-type APC allele. Finally, the forced expression of RSPO fusion proteins were shown to endow colorectal cells with an increased growth ability. These results suggest that the expression of RSPO fusion transcripts is related to a subset of CRCs arising in the Japanese population.

Uniportal Video-Assisted Thoracoscopic Segmentectomy for Early-Stage Non-Small Cell Lung Cancer: Overview, Indications, and Techniques.

Twenty years have passed since uniportal video-assisted thoracoscopic surgery (VATS) was first reported. Several reports have already proven the minimal invasiveness of uniportal VATS. In addition, two large clinical trials recently demonstrated the benefits of segmentectomy for small peripheral early-stage non-small cell lung cancer. Uniportal VATS segmentectomy is considered the most beneficial minimally invasive surgery for patients with early-stage lung cancer. However, a high level of skill and experience are required to achieve this goal. Only a few reports have discussed specific techniques, particularly for complex segmentectomies. In this Special Issue, we reviewed previous reports on uniportal VATS segmentectomy regarding the indications, instrument selection, marking of the tumor location, methods of intersegmental plane identification, and lymph node dissection, including our own techniques with video content.

Physical activity in patients with non-small cell lung cancer after lung resection.

BACKGROUND: Lung resection is the standard of care for patients with clinical stage I/II non-small cell lung cancer. This surgery reduces both the duration and quality of patients' daily ambulatory activities 1 month after surgery. However, little is known about physical activity after lung resection in patients with lung cancer. To evaluate the recovery process of physical activity with pulmonary rehabilitation in patients after lung resection and examine whether physical activity is affected by age. METHODS: In this prospective, observational study, we measured and analysed participants' postoperative physical activity using a uniaxial accelerometer daily from postoperative day 1 to 30. FINDINGS: We analysed 99 patients who underwent thoracic surgery. The number of walking steps significantly increased until day 4 and then reached a plateau thereafter. The duration of exercise at <3 metabolic equivalents significantly increased until day 3, and no significant difference was observed thereafter. Exercise at >3 metabolic equivalents significantly increased until day 4 and reached a plateau thereafter. A significant correlation was observed between age and number of steps after day 4. Compared with video-assisted thoracoscopic surgery, thoracotomy significantly decreased the number of steps from day 3 to 4. INTERPRETATION: We found that the level of physical activity varied by index in patients with non-small cell lung cancer who underwent lung resection. Age and surgical procedure affect different periods with the increase in post-operative walking steps.

Airway stent intervention in a high-volume center: safe procedures and educational perspectives.

Background: Airway intervention, including stenting, can rapidly improve a patient's respiratory condition, but the procedure requires highly specialized techniques and expertise. Therefore, educating young endoscopists and passing on the techniques are major issues. However, the best way to educate new doctors on these techniques remains unclear. This study analyzed our educational system for airway intervention and its outcomes. Methods: Patients who underwent airway intervention regarding airway stents under general anesthesia in our department between January 2010 and September 2023 were included. The outcomes of interventions related to airway stents in our hospital were evaluated retrospectively, including from an educational perspective. Results: A total of 96 patients (76 undergoing stenting for airway stenosis, 8 stenting for airway-esophageal fistula, and 12 stent removal) were analyzed. The median experience level of the main physician was 5 (range, 1-17) years, and that of the supervising physician was 18 (range, 5-23) years. The median number of physicians who participated in the interventions was four. A rigid bronchoscope was used in 86.5% of cases. The procedure success rate was 95.8%. Intraoperative complications occurred in 8.3% and postoperative complications in 10.5% of cases, and there was 1 procedure-related death (1.3%). In the analysis of factors related to the development of complications, the years of experience of the main physician had no influence. Conclusions: These findings indicate that our method of airway intervention is safe. Young endoscopists were able to master the technique by gaining experience under the supervision of experts.

NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.

The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.

Identification and association study with lung cancer for novel insertion polymorphisms of human endogenous retrovirus.

Sequences of human endogenous retroviruses (HERVs) are members of the long terminal repeat (LTR) retrotransposon family. Although the expression of HERV has long been a topic of investigation, HERV-insertion polymorphisms are not well known, and a genetic association between HERV-insertion polymorphisms and cancer has never been reported. To identify novel HERV loci in the genome from cancer tissues, we carried out the inverse PCR method targeting a conserved LTR region of HML-2, which is the most recently acquired HERV group. Novel two insertions, HML-2_sLTR(1p13.2) and HML-2_sLTR(19q12), were identified as insertionally polymorphic solo LTRs. Furthermore, a significant prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in female never-smoking patients aged 60 years and over who had lung adenocarcinoma [versus the other genotyping; odds ratio (OR): 1.97; 95% confidence interval (CI): 1.01-3.81]. In another cohort consisting of female never-smoking patients with lung adenocarcinoma, a prevalence of HML-2_sLTR(1p13.2) homozygosity tended to be high in patients aged 60 years and over (versus the other genotyping; OR: 2.03; 95% CI: 0.96-4.29), whereas a low prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in patients <60 years old (versus the other genotyping; OR: 0.31; 95% CI: 0.11-0.94). Our results suggest that HML-2_sLTR(1p13.2) is involved with the susceptibility to lung adenocarcinoma in female never-smokers in an age-dependent manner and that other HERV polymorphisms related to human diseases might remain to be identified in the human genome.