Factors affecting the short-term outcomes of robotic-assisted thoracoscopic surgery for lung cancer.

PURPOSE: Robotic-assisted thoracoscopic surgery (RATS) is a relatively new approach to lung cancer surgery. To promote the development of RATS procedures, we investigated the factors related to short-term postoperative outcomes. METHODS: We analyzed the records of patients who underwent RATS lobectomy for primary lung cancer at our institution between June, 2018 and January, 2023. The primary outcome was operative time, and the estimated value of surgery-related factors was calculated by linear regression analysis. The secondary outcome was surgical morbidity and the risk was assessed by logistic regression analysis. RESULTS: The study cohort comprised 238 patients. Left upper lobectomy had the longest mean operative time, followed by right upper lobectomy. Postoperative complications occurred in 13.0% of the patients. Multivariate analysis revealed that upper lobectomy, the number of staples used for interlobular fissures, and the number of cases experienced by the surgeon were significantly associated with a longer operative time. The only significant risk factor for postoperative complications was heavy smoking. CONCLUSION: Patients with well-lobulated middle or lower lobe lung cancer who are not heavy smokers are recommended for the introductory period of RATS lobectomy. Improving the procedures for upper lobectomy and dividing incomplete interlobular fissures will promote the further development of RATS.

Safety and efficacy of new staple-line reinforcement in lung resection: a prospective study of 48 patients.

PURPOSE: To evaluate the safety and efficacy of new staple-line reinforcement (SLR) in pulmonary resection through a prospective study and to compare the results of this study with historical control data in an exploratory study. METHODS: The subjects of this study were 48 patients who underwent thoracoscopic lobectomy. The primary endpoint was air leakage from the staple line. The secondary endpoints were the location of air leakage, duration of air leakage, and postoperative pulmonary complications. RESULTS: The incidence of intraoperative air leakage from the staple line was 6.3%. Three patients had prolonged air leakage as a postoperative pulmonary complication. No malfunction was found in patients who underwent SLR with the stapling device. When compared with the historical group, the SLR group had a significantly lower incidence of air leakage from the staple line (6.3% vs. 28.5%, P < 0.001) and significantly shorter indwelling chest drainage time (P = 0.049) and length of hospital stay (P < 0.001). CONCLUSIONS: The use of SLR in pulmonary resection was safe and effective. When compared with conventional products, SLR could control intraoperative air leakage from the staple line and shorten time needed for indwelling chest drainage and the length of hospital stay.

Comparable efficacy and safety of COVID-19 vaccines for patients receiving tegafur-uracil as postoperative adjuvant chemotherapy.

PURPOSE: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. METHODS: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. RESULTS: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. CONCLUSIONS: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. CLINICAL TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

A novel EWSR1-VGLL1 gene fusion in a soft tissue malignant myoepithelial tumor.

Soft tissue myoepithelial tumors are very rare mesenchymal tumors that are currently categorized as miscellaneous neoplasms with uncertain differentiation. Although the molecular pathogenesis of soft tissue myoepithelial tumors remains unclear, EWSR1 gene fusions with a variety of partner genes are regarded as one of the major pathogenic driver events in these tumors. We herein present a case of a deep soft tissue malignant myoepithelial tumor arising in the thigh with multiple pulmonary metastases. This tumor displayed diverse and unique histological features, namely, an epithelioid glandular growth pattern, pseudorosette-like formation, and a diffuse nest and cord-like pattern within an abundant myxoid matrix. Next-generation RNA sequencing identified a novel fusion transcript, in which the in-frame junctional reads contained exon 9 of EWSR1 and exon 2 of VGLL1, resulting in the formation of a putative chimeric protein with the N-terminal transcriptional activation domain of EWSR1 and C-terminal full length of the VGLL1 protein. EWSR1-VGLL1 fusion has not been described in neoplasm before. Further molecular and functional experiments on the present EWSR1-VGLL1 fusion gene are required to elucidate its tumorigenic effect.

Insulinoma-associated protein 1 is a prognostic biomarker in pulmonary high-grade neuroendocrine carcinoma.

BACKGROUNDS AND OBJECTIVES: Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of pulmonary neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with pulmonary high-grade neuroendocrine carcinomas (HGNEC) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients. METHODS: Seventy-five consecutive patients with HGNEC who underwent complete surgical resections from January 2000 to December 2018 were enrolled in this study. We classified these patients into two groups: the INSM1-positive group (n = 59) and INSM1-negative group (n = 16). We compared the clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) between the groups. In addition, we performed univariate and multivariate analyses to identify the prognostic factors associated with postoperative survival. RESULTS: Significant differences in tumor diameter and vascular invasion between the groups were found. OS and RFS were significantly poorer in the INSM1-positive group than in the INSM1-negative group. Univariate and multivariate analyses revealed that INSM1 expression was the strongest predictor of poor prognosis for OS and RFS. CONCLUSIONS: INSM1 expression had the greatest influence on the prognosis in patients with HGNEC and may be a prognostic biomarker in these patients.

[Tumor-induced Hypophosphatemic Osteomalacia Caused by a Chest Wall Tumor].

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disease characterized by hypophosphatemia and skeletal undermineralization. Overproduction of fibroblast growth factor 23( FGF23) from the responsible tumor is reported to be a causative factor. Removing the tumor is the only effective treatment for TIO, but identifying the tumor is sometimes difficult. A 43-year-old man complained of heel pain 4 years earlier, and the pain gradually expanded to the whole body. As a blood test showed the elevation of the serum FGF23 level and hypophosphatemia, he was diagnosed with FGF23-related hypophosphatemia. Chest computed tomography (CT) showed a 10-mm nodule in the right chest wall. Venous sampling for FGF23 revealed considerable elevation of the FGF23 level in the right subclavian vein. Therefore, a chest wall tumor was suspected as the tumor responsible for TIO, and surgical resection was performed. After surgery, hypophosphatemia improved within several days, and the FGF23 level also normalized.

[Mediastinal Shift Due to the Rapidly Expanded Giant Bulla Probably Caused by the Lung Cancer].

A 39-year-old man was admitted to our hospital with back pain and numbness of the left leg. Computed tomography (CT) showed a giant bulla and tumor in the right lung, mediastinal shift to the left side and lesions suggestive of metastatic sacral tumor. Three days later, the patient visited the emergency room with dyspnea and tachycardia. Chest CT showed the progression of mediastinal shift due to the rapid expansion of the giant bulla, and an emergency surgery was performed. After induction of anesthesia, sudden respiratory and circulatory failure occurred. Considering further expansion of the giant bulla by positive pressure ventilation, veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) was applied. After establishing ECMO, the condition of the patient became stable and the giant bulla could be resected successfully.

[Temporary Bypass with 5-Fr Catheter for Reconstruction of Superior Vena Cava].

A 21-year-old man was referred to our hospital because of an abnormal shadow on a routine chest radiogram. Enhanced computed tomography showed an 83×74 mm mass in the anterior mediastinum, with invasion of the superior vena cava (SVC). Surgical resection with sternotomy was performed. Intraoperative temporary bypass grafting with a 5-Fr catheter was performed between the right brachiocephalic vein and right atrium. The mediastinal tumor was resected with the SVC, and SVC reconstruction with a 16 mm expanded polytetrafluoroethylene graft was performed. The bypass stabilized intraoperative vital signs and enabled safe completion of the operation. The pathological diagnosis was seminoma. SVC replacement combined with temporary bypass using a small diameter catheter is technically feasible and safe.

[Successful Treatment of a Patient with Idiopathic Subglottic Stenosis].

Idiopathic subglottic stenosis (ISS) is defined as the narrowing of the upper airway without any known cause. A 40-year-old female was referred to our hospital with the complaint of exacerbation of dyspnea causing difficulty in going out. Chest computed tomography (CT) scan and bronchoscopy revealed subglottic tracheal stenosis with a luminal diameter of 5 mm at the narrowest part. Tracheal mucosa of the stenotic lesion was smooth, and the patient had no previous medical history. Subglottic tracheal resection of the stenotic lesion and reconstruction were performed. The postoperative course was good, and the symptom of dyspnea improved significantly. Recently, some reports have suggested conservative treatments such as laser and balloon dilation for ISS, but the recurrence rate after these treatments is still high. Surgery is recommended rather than conservative treatments for patients with less severe inflammation of tracheal mucosa and other comorbidities like present case.

Significant role of Psf3 expression in non-small-cell lung cancer.

The GINS complex associates with cell division cycle (Cdc) protein 45 and mini-chromosome maintenance (Mcm) proteins 2-7 to form the Cdc45-Mcm-GINS (CMG) complex, which is essential for DNA duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non-small-cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression.

[Perforation of the Mediastinal Mature Teratoma;Report of a Case].

The mediastinal mature teratoma is uncommon in adult and sometimes ruptures. We present a case of perforation of mediastinal mature teratoma. A 22-year-old man, who had been scheduled for surgery to resect anterior mediastinal teratoma, was referred to our hospital due to sudden chest pain. The enhanced computed tomography findings suggested a perforation of the teratoma and the emergency surgery was performed. Extirpation of the tumor with partial resection of right upper lung, pericardium, and superior vena cava was performed. The histological diagnosis was mature teratoma and the defect of the mediastinal pleura was found to be the site of perforation. The patient was well and discharged from the hospital without complications.

The role of Necl-5 in the invasive activity of lung adenocarcinoma.

Nectin-like molecule-5 (Necl-5) is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor and is often upregulated in cancer cells. It has been said that Necl-5 plays a role in not only cell-cell adhesion, but also cell migration, proliferation, and metastasis. In this study, we used a bronchioloalveolar carcinoma (BAC) cell line and fibroblasts to assess the expression of Necl-5 in the development of cancer-stroma communication by using an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) system that enables visualization of cell migration during invasion. The expression of Necl-5 was higher in BAC cells than in fibroblasts. This tendency didn't change even when the BAC cells were mixed with fibroblasts. To assess the role of Necl-5 in the invasive activity of the BAC cells, we knocked down its expression using RNA interference (RNAi). The invasion assay with DL-CGH revealed that inhibition of Necl-5 expression in the BAC cells was associated with suppressed invasiveness. In addition, Necl-5 knockdown inhibited the movement and proliferation of the BAC cells. Necl-5 expression in lung cancer cells is crucial for their invasiveness in the cancer-stromal interaction, suggesting that Necl-5 could be a favorable molecular target for the suppression of invasiveness in lung adenocarcinoma.

Console and bedside surgeon fused robot-assisted thoracic surgery.

In the last decade, even thoracic surgery has seen an increase in the use of robotic surgical systems, and robot-assisted thoracic surgery (RATS) is considered one of the main issues. While RATS is associated with solo manipulative freedom and high-definition optical systems, several disadvantages, such as the lack of tactile sensation and difficult learning curves for the whole team, have been raised. Therefore, to overcome these issues, we developed a 'fusion surgery' approach combining a robotic procedure with manual maneuvers, where the table surgeon retracts the lung and staples the pulmonary vasculature and bronchus. Herein, we introduce our 'fusion surgery' procedure and elaborate on its advantage from technical and educational perspectives.

Programmed death ligand-1 expression and occult lymph node metastasis in non-small cell lung cancer.

BACKGROUND: Identifying the preoperative risk factors for lymph node upstaging could contribute to the development of individualized perioperative treatment for patients with non-small cell lung cancer (NSCLC). The current study aimed to evaluate the risk factors for lymph node upstaging, including gene mutation and programmed death ligand-1 expression in patients with resectable NSCLC. METHODS: Data on the clinicopathological characteristics of patients who underwent lobectomy for clinical N0 NSCLC at our institution were collected. The clinicopathological findings of the pathological N0 and lymph node upstaging groups were then analyzed. Univariate and multivariate analyses were performed to examine the predictive factors for nodal upstaging. RESULTS: Of 291 patients, 40 had postoperative nodal upstaging (n = 25, N1; n = 15, N2). Large tumor size and high maximum standardized uptake value were significantly associated with nodal upstaging. The nodal upstaging group had a higher proportion of patients with solid adenocarcinoma and lymphatic, vascular, and pleural invasion than the pathological N0 group. Further, the nodal upstaging group had a higher proportion of patients with positive programmed death ligand-1 expression than the pathological N0 group. Univariate and multivariate analyses showed that tumor size and positive programmed death ligand-1 expression were associated with nodal upstaging. CONCLUSION: The appropriate therapeutic strategy including preoperative treatment and resection should be cautiously considered preoperatively in patients with clinical N0 NSCLC who have large tumors and positive programmed death ligand-1 expression.

[Lung cancer incidentally detected at the treatment of pneumothorax ; report of two cases].

We report 2 cases of lung cancer incidentally detected following pneumothorax. Case 1:A 40-year-old man complaining of dyspnea was admitted with right pneumothorax. Chest computed tomography (CT) after chest drainage showed a cavitary nodule with pleural indentations in the right lower lobe. It was indicated at surgery that pneumothorax was caused by perforation of the tumor into the pleural cavity. Right lower lobectomy was performed because the pathological diagnosis of the nodule was a large cell carcinoma. The final histopathological diagnosis was stage II A (pT2aN1M0). The patient died of recurrence 14 months after surgery. Case 2:A 47-year-old man who admitted with right pneumothorax was found to have a nodule with pleural indentations closely a bulla at the apex of the right lung by chest CT after chest drainage. Pneumothorax was indicated to be caused by rupture of the bulla at surgery. Right upper lobectomy was performed because the pathological diagnosis of the nodule was a squamous carcinoma. The final histopathological diagnosis was stage I A (pT1bN0M0). The patient is alive at 2 years after the operation without recurrence. Lung cancer detected following pneumothorax which was caused by perforation of the tumor is generally considered to have poor prognosis. Whereas, prognosis of lung cancer incidentally detected following pneumothorax depends on its staging.

Oxidized Regenerated Cellulose Sheets in Postoperative Intrathoracic Adhesions.

Adhesiolysis is often necessary in intrathoracic adhesion during ipsilateral repeat lung resection. This procedure has a risk of surgical complications, including unintentional intraoperative damage of the pulmonary vessels or lung parenchyma. We used an oxidized regenerated cellulose (ORC) sheet to prevent intrathoracic adhesion after lung resection in 55 patients. The sheet was placed on the surface of the resected region and on the lung surface under the wound. No major postoperative complications were observed. Three cases underwent ipsilateral thoracic surgery for the treatment of lung malignancies, and there were no intrathoracic adhesions around the ORC sheet-covered area.

Prognostic value of preoperative plasma fibrinogen levels in resected stage I non-small cell lung cancer.

BACKGROUND: The number of surgical procedures has increased among patients with early-stage lung cancer. If the poor prognostic factors for stage I non-small cell lung cancer (NSCLC) can be simply validated preoperatively, appropriate treatment will be provided. The current study aimed to evaluate the prognostic value of preoperative plasma fibrinogen levels in patients with resected stage I NSCLC. METHODS: We retrospectively analyzed the clinicopathological information of patients (n = 149) who underwent lobectomy for stage I NSCLC between May 2014 and July 2016. Data about peripheral blood analysis, histopathological finding, and follow-up assessment results were collected from the databases. Patients were divided into the low and high fibrinogen groups. Univariate and multivariate analyses were performed to evaluate the predictors of recurrence and survival. RESULTS: Compared with the low fibrinogen group (<377 mg/dl), the high fibrinogen group (≥377 mg/dl) had a significantly greater number of male participants (p = 0.04), smokers (p < 0.001), and those with elevated cytokeratin antigen levels (p = 0.04), lymphatic invasion (p = 0.007), and squamous cell carcinoma (p < 0.001). Plasma fibrinogen level was considered a significant independent factor for recurrence and overall survival on both the univariate and multivariate analyses (p < 0.001 and p = 0.010) and the multivariate analysis alone (p = 0.020 and p < 0.012). CONCLUSION: Preoperative plasma fibrinogen level might be a useful predictor of recurrence and survival in patients with stage I NSCLC. The treatment strategy for patients with high fibrinogen levels could be cautiously considered preoperatively.

Successful treatment of refractory empyema using dual sheet covering.

Managing thoracic empyema with massive air leakage can be challenging. We present a case with thoracic empyema with multiple bronchopleural fistulae and extensive lung parenchymal necrosis due to drain injury. Emergency surgery was performed for respiratory distress due to massive air leakage. As direct sutures could not be achieved due to extensive parenchymal necrosis, polyglycolic acid and oxidized regenerated cellulose sheets were packed into the lesion. Although open-window thoracostomy was required for bronchopleural fistulae, the stoma closure was achieved via vacuum-assisted closure therapy. The dual sheet coverings contributed to the successful recovery by resolving multiple bronchopleural fistulae.

Effect of myasthenia gravis on the surgical outcomes of patients with thymoma.

BACKGROUND: Myasthenia gravis (MG) is the most common paraneoplastic syndrome in thymoma. However, the association between MG and postoperative outcomes is controversial. Therefore, we examined the effect of MG on the surgical outcomes of patients with thymoma. METHODS: This study enrolled 145 consecutive patients with thymoma who underwent surgical resection at our institution between January 2000 and December 2020. The patients were classified into thymoma with MG (MG group) and without MG (non-MG group). Data about characteristics of patients, surgical outcomes, and prognostic factors were compared between the two groups. RESULTS: Of 145 patients, 47 (32%) presented with MG and 98 (68%) did not. There was no significant difference in terms of the incidence of postoperative complications, overall survival (OS), and recurrence-free survival (RFS) between the two groups. The deaths were not caused by thymoma. Among the patients aged >60 years, the MG group had a lower survival rate than the non-MG group. In the univariate analysis, age ≥60 years was a poor prognostic factor for OS, whereas in the multivariate analysis, Masaoka stage III and IV classifications were poor prognostic factors for RFS. CONCLUSION: The incidence of postoperative complications did not differ between patients with thymoma and without MG. In the MG group, age ≥60 years was a poor prognostic factor for OS. The postoperative follow-up of patients aged ≥60 years with thymoma with MG should focus on not only recurrence but also progression of diseases other than thymoma.

[Mediastinal goiter; report of a case].

A 76-year-old female was admitted to our hospital because of an abnormal shadow on chest computed tomography (CT) which showed the tumor extending from left lower end of the thyroid to the aortic window along the left side of the trachea, indicating the retrosternal goiter. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were within normal ranges. The tumor was resected through cervical collar incision and median sternotomy. The pathological diagnosis was an adenomatous goiter. The patient was discharged without complications.