Prognostic Outcome of Pulmonary Resection for Pulmonary Metastases from Gastric Cancer.

PURPOSE: Regardless of the devastating outcomes of pulmonary resection for metastases from gastric cancer, a handful of patients survive long after pulmonary metastasectomy. This study aimed to identify a good candidate for pulmonary resection for metastases from gastric cancer. METHODS: Between 2005 and 2023, 564 patients underwent pulmonary metastasectomy in our department, of which 12 patients underwent pulmonary resection for metastases from gastric cancer. Variables evaluated were the number and size of metastatic lesions, surgical procedure, disease-free interval (DFI), and the serum carcinoembryonic antigen at pulmonary metastasectomy. RESULTS: The DFI following gastrectomy ≤12.5 months group had a significantly worse overall survival (OS) than the other group (p = 0.005). A comparison between DFI following gastrectomy ≤12.5 months group and DFI following gastrectomy >12.5 months group showed a significant difference in serum carcinoembryonic antigen (CEA) value at pulmonary metastasectomy (p = 0.048). The serum CEA value at pulmonary metastasectomy >5.8 ng/ml group had a significantly worse OS than the other group (p = 0.001). CONCLUSION: Pulmonary metastasectomy can be indicated in some patients with metastasis from gastric cancer who have longer DFI from gastrectomy and lower serum CEA at pulmonary metastasectomy.

Prognostic significance of preoperative to postoperative serum carcinoembryonic antigen ratio after lobectomy for lung adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. METHODS: Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. RESULTS: Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2 ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2 ng/ml (n = 28). Patients with postoperative CEA > 6.2 ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. CONCLUSION: The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2 ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

A case of attempted transbronchial spigot insertion for fistulous pyothorax in the residual pleural airspace after pleurectomy/decortication for malignant pleural mesothelioma.

Pleurectomy/decortication for malignant pleural mesothelioma is a relatively recent surgical approach for which there is a dearth of information on complications, especially in the late postoperative period. A 70-year-old man was diagnosed with right epithelioid malignant pleural mesothelioma and underwent pleurectomy/decortication. Computed tomography at 6 months after surgery revealed nodules on the surface of the right lung. These nodules gradually increased in size and were diagnosed as recurrent disease. Immunotherapy was started, but treatment was discontinued a few days after the first course due to pneumonitis. Subsequent oral prednisolone therapy for about 2 months ameliorated pneumonitis, but fistulous pyothorax developed. During attempted transbronchial occlusion of the responsible bronchus, some spigots penetrated the empyema cavity. Open window thoracotomy was performed on the following day. This case suggests that if there is no change in diameter between the proximal and distal parts of the responsible bronchus, transbronchial occlusion should not be chosen.

Effect of Tegafur-Uracil in Resected Stage IB Lung Adenocarcinoma According to Presence or Absence of Epidermal Growth Factor Receptor Gene Mutation: A Retrospective Cohort Study.

PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.

Successful Treatment with Osimertinib Based on Therapeutic Drug Monitoring in a Hemodialysis Patient with Non-Small Cell Lung Cancer: A Case Report.

Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.

Clinical Significance of Nodal DCsign Expression in Non-small-cell Lung Cancer Patients.

BACKGROUND/AIM: Dendritic cells (DCs) are difficult to evaluate in lung regional lymph nodes because of region-specific structures, such as abundant trabeculae connecting the medullary and subcapsular sinuses, the latter of which contains few anthracotic macrophages. Therefore, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DCsign)-positive DCs and CD68-positive macrophages are unlikely to show a typical distribution. The present study therefore explored quantitative factors connecting the nodal DC morphology to the patient outcome. MATERIALS AND METHODS: Lymph nodes from 34 non-small-cell lung cancer patients who underwent complete resection were used for immunohistochemical assessments of DCsign and CD68 and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Preoperative patient blood samples were used for the quantitative evaluation of monocytes. RESULTS: The nodal DCs showed a complementary distribution with macrophages, thus few DCs were seen in clusters of macrophages. DCs often presented as a mesh-like rosette that was solitary or connected to a DC cluster. DCs disappeared, and some macrophages were apoptotic when surrounded by cancer cells that have metastasized to lymph nodes. The proportional area of a DC cluster was significantly associated with the histological differentiation of cancer (p=0.013), with a higher ratio tending to lead to a better overall survival (p=0.059), and significantly so in adenocarcinoma (p=0.007). The rosette number was significantly correlated with the smoking index and blood monocyte number (p=0.013 and p=0.005, respectively). CONCLUSION: The nodal DC morphology appears useful as a prognostic factor and may lead to a new phase of clinicopathological studies of solid cancers.

Extracellular volume fraction derived from equilibrium contrast-enhanced CT as a diagnostic parameter in anterior mediastinal tumors.

PURPOSE: To assess the usefulness of extracellular volume (ECV) fraction derived from equilibrium contrast-enhanced CT (CECT) for diagnosing anterior mediastinal tumors. METHOD: This study included 161 histologically confirmed anterior mediastinal tumors (55 low-risk thymomas, 57 high-risk thymomas, 32 thymic carcinomas, and 17 malignant lymphomas) that were assessed by pretreatment CECT. ECV fraction was calculated using measurements obtained within the lesion and the aorta on unenhanced and equilibrium phase CECT. ECV fraction was compared among anterior mediastinal tumors using one-way ANOVA or t-test. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the ability of ECV fraction to differentiate thymic carcinomas/lymphomas from thymomas. RESULTS: ECV fraction differed significantly among the anterior mediastinal tumors (p < 0.001). ECV fraction of thymic carcinomas was significantly higher than those of low-risk thymomas, high-risk thymomas, and lymphomas (p < 0.001, p < 0.001, and p = 0.006, respectively). ECV fraction of lymphomas was significantly higher than that of low-risk thymomas (p < 0.001). ECV fraction was significantly higher in thymic carcinomas/lymphomas than in thymomas (40.1 % vs. 27.7 %, p < 0.001). The optimal cutoff value to differentiate thymic carcinomas/lymphomas from thymomas was 38.5 % (AUC, 0.805; 95 %CI, 0.736-0.863). CONCLUSIONS: ECV fraction derived from equilibrium CECT is helpful in diagnosing anterior mediastinal tumors. High ECV fraction is indicative of thymic carcinomas/lymphomas, particularly thymic carcinomas.

Clinical significance of ALKBH4 expression in non-small cell lung cancer.

Background: Gene methylation is deeply involved in epigenetics and affects both the development and maintenance of homeostasis and carcinogenesis. ALKBH4 is a member of the AlkB homolog (ALKBH) family that controls demethylation of DNA and RNA. Methods: This study enrolled 160 patients with non-small cell lung cancer (NSCLC) who underwent complete resection. The expression of ALKBH4 in cancer tissue was evaluated by immunohistochemistry. The correlation among the expression of ALKBH4, clinicopathological factors, and prognostic outcome was evaluated. Results: In the NSCLC clinical samples, the expression of ALKBH4 was identified not only in cell membranes but also in the cytoplasm of cancer cells. In 140 of 160 cases, ALKBH4 was more highly expressed in the cancerous tissue than in the surrounding normal tissue. The proportion of cancer cells expressing ALKBH4 was higher in adenocarcinoma than in other histological types. In addition, the expression intensity of ALKBH4 in each cancer cell was also stronger in adenocarcinoma than in squamous cell carcinoma. The expression of ALKBH4 was not associated with clinicopathological factors, except for histological type. In adenocarcinoma, the recurrence-free survival (RFS) and overall survival (OS) rates were significantly lower in the ALKBH4-positive group than in the ALKBH4-negative group (P=0.008, 0.031, respectively). A multivariate logistic regression analysis indicated that the ALKBH4 expression was an independent prognostic factor for RFS (P=0.003) and OS (P=0.013). The expression of ALKBH4 was observed in all four patients with adenocarcinoma in situ. Conclusions: The ALKBH4 expression may be a useful predictor of the postoperative outcomes of lung adenocarcinoma (LUAD) patients.

Hemodynamic features underlying pulmonary vein stump thrombus formation after left upper lobectomy: four-dimensional flow magnetic resonance imaging study.

BACKGROUND: We previously reported that to-and-fro blood movement near the pulmonary vein stump was particularly prominent after left upper lobectomy compared with other lobectomy, which may be the cause of the high susceptibility of pulmonary vein thrombus after left upper lobectomy. The aim of the present study was to compare the hemodynamics in patients who developed pulmonary vein thrombus after left upper lobectomy with those in patients who did not develop pulmonary vein thrombus using four-dimensional flow magnetic resonance imaging (4D MRI). METHODS: This was a retrospective evaluation of a prospectively collected clinical and radiological database of 37 patients who underwent 4D MRI 7 days after left upper lobectomy for lung cancer (n=37). We obtained two parameters by 4D MRI: the grade of to-and-fro blood movement and the flow energy loss around the pulmonary vein stump. The length of the pulmonary vein stump, a known risk factor for pulmonary vein thrombus, was also measured. RESULTS: According to a scatterplot of the grade of to-and-fro blood movement versus the flow energy loss, patients with pulmonary vein thrombus (n=15) were concentrated in an area which appears to be a 'dangerous' hemodynamic condition. There were few patients without pulmonary vein thrombus in this 'dangerous' area, except for one who unfortunately developed delayed pulmonary vein thrombus and cerebral infarction. We proposed a formula using the 4D MRI-derived parameters based on a stepwise multiple regression analysis that was more closely associated with the development of pulmonary vein thrombus than the length of the pulmonary vein stump (area under the receiver operating characteristics curve: 0.918 vs. 0.705, P=0.0500). CONCLUSIONS: We proposed the existence of a 'dangerous' hemodynamic condition responsible for pulmonary vein thrombus formation. 4D MRI before the development of pulmonary vein thrombus may help identify patients requiring preventive therapy against pulmonary vein thrombus and subsequent thromboembolic complications.

ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer.

The human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via cell cycle arrest at the G1 phase of in vivo tumour growth. ALKBH4 knockdown downregulated E2F transcription factor 1 (E2F1) and its target gene expression in NSCLC cells. ALKBH4 and E2F1 expression was significantly correlated in NSCLC clinical specimens. Moreover, patients with high ALKBH4 expression showed a poor prognosis, suggesting that ALKBH4 plays a pivotal tumour-promoting role in NSCLC.

Four-dimensional flow magnetic resonance imaging study to explain high prevalence of pulmonary vein stump thrombus after left upper lobectomy.

BACKGROUND: Pulmonary vein (PV) stump thrombus, a known source of cerebral infarction, develops almost exclusively after left upper lobectomy; however, the mechanism remains unclear. We therefore evaluated the hemodynamics in the left atrium with four-dimensional flow magnetic resonance imaging (4D-flow MRI), which enables the simultaneous depiction of blood flow at three locations and the evaluation of hemodynamics. METHODS: 4D-flow MRI was basically performed 7 days after lobectomy for cancer arising in the right upper lobe (n=11), right lower lobe (n=8), left upper lobe (n=13), or left lower lobe (n=8). We evaluated dynamic blood movement from the ipsilateral remaining PV, the resected PV stump, and the contralateral PVs into the left atrium using 4D-flow MRI. RESULTS: There were some characteristic blood flow patterns that seemed to either promote or prevent PV stump thrombus. Promotive flow patterns were significantly more frequent and preventive flow patterns were significantly less frequent in patients who had undergone left upper lobectomy than in those who had undergone other lobectomy. Accordingly, the degree of blood turbulence near the vein stump, as measured by the extent of change in the blood movement, was significantly higher in patients who had undergone left upper lobectomy than in patients who had undergone other lobectomy. CONCLUSIONS: Our study revealed that left upper lobectomy likely causes blood turbulence near the vein stump through complicated blood streams in the left atrium, which can play a part in the development of vein stump thrombus. Further study to identify patients at high risk of vein stump thrombus is warranted.

Targeted Therapy Followed by Cytotoxic Chemotherapy in Preoperative Patients With Locally Advanced Lung Adenocarcinoma.

BACKGROUND: Although oncogene-targeted therapy is a first-line treatment for advanced, unresectable lung adenocarcinoma harboring a target gene mutation, its effect on potentially resectable, locally advanced lung adenocarcinoma remains unclear. PATIENTS AND METHODS: Ten patients with clinically diagnosed stage III lung adenocarcinoma harboring a target gene mutation were enrolled in the current feasibility study of targeted therapy followed by cytotoxic chemotherapy (platinum and pemetrexed) before radical surgery. RESULTS: Complete resection was accomplished in all nine patients who went on to surgery (one patient refused surgery), and all of these patients recovered without major postoperative complications. Overall, almost all of the patients who underwent surgery remain disease-free after a median follow-up of 22 months since the initial treatment, with only one patient dying of recurrence. CONCLUSION: Radical surgery after the sequential use of cytostatic and cytotoxic drugs resulted in a favorable short-term outcome.

Thoracoscopic en bloc resection of left upper lobe lung cancer.

In this video tutorial we demonstrate our procedure for en bloc resection of the left upper lobe and the regional lymph nodes via video-assisted thoracic surgery in patients with primary lung cancer and outline some key surgical points. First, the operation should start with dissection of the posterior portion of the hilar and lower paratracheal nodes, which will provide excellent visualization of the left recurrent laryngeal nerve and also facilitate dissection of the subaortic and para-aortic (aorto-pulmonary) nodes. Second, the lower paratracheal nodes and aorto-pulmonary nodes should be mobilized together with their dominant lymphatic drainage pathways from the left upper lobe. During this procedure, care must be taken not to divide the peribronchial lymphatic pathway toward the lower paratracheal nodes or the subpleural lymphatic pathway toward the aorto-pulmonary nodes.  By following these guidelines, the left upper lobe and the regional lymph nodes can be resected en bloc without any division of their lymphatic connection. We believe that this procedure will help prevent pleural dissemination as well as prevent the surgeon's missing any metastatic lymph nodes.

Thoracoscopic en bloc resection of left upper lobe lung cancer.

In this video tutorial we demonstrate our procedure for en bloc resection of the left upper lobe and the regional lymph nodes via video-assisted thoracic surgery in patients with primary lung cancer and outline some key surgical points. First, the operation should start with dissection of the posterior portion of the hilar and lower paratracheal nodes, which will provide excellent visualization of the left recurrent laryngeal nerve and also facilitate dissection of the subaortic and para-aortic (aorto-pulmonary) nodes. Second, the lower paratracheal nodes and aorto-pulmonary nodes should be mobilized together with their dominant lymphatic drainage pathways from the left upper lobe. During this procedure, care must be taken not to divide the peribronchial lymphatic pathway toward the lower paratracheal nodes or the subpleural lymphatic pathway toward the aorto-pulmonary nodes.  By following these guidelines, the left upper lobe and the regional lymph nodes can be resected en bloc without any division of their lymphatic connection. We believe that this procedure will help prevent pleural dissemination as well as prevent the surgeon's missing any metastatic lymph nodes.

Crucial role of angiography in the surgical planning of a pulmonary artery aneurysm.

A 46-year-old woman was found to have an aneurysm of the superior segmental pulmonary artery in the right lower lung lobe on computed tomography images. Moreover, angiography revealed dilated bronchial arteries flowing into the aneurysm with neovascularization, and the contrast medium was partially pooled in the basal segment of the same lobe. The patient's hemoptysis could not be controlled by an interventional radiology procedure. Therefore, lobectomy was carried out instead of aneurysmectomy. There has been no recurrence for 4 years after surgery. We considered that that angiographic information allowed for the most appropriate operation in this case.