Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study.

PURPOSE: Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy. METHODS: This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors. RESULTS: Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence. CONCLUSION: Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.

Localization of macrophages and dendritic cells in human thoracic lymph nodes: An immunohistochemical study using surgically obtained specimens.

Both dendritic cells (DCs) and macrophages are bone marrow-derived cells that perform antigen presentation. The distribution of DCs and CD68-positive macrophages were immunohistochemically examined in 103 thoracic nodes obtained from 23 lung cancer patients (50-84 years old) without metastasis. Among three antibodies tested initially-CD209/DCsign, fascin, and CD83-DCsign was chosen as the DC marker. For comparison, 137 nodes from 12 patients with cancer metastasis were also examined histologically. In patients without metastasis, DCs were found as (1) clusters along the subcapsular sinus and in a border area between the medullary sinus and cortex (mean sectional area of multiple nodes at one site, 8.4%) and, (2) rosette-like structures in the cortex (mean number in multiple nodes at one site, 20.5). Notably, DC clusters and rosettes contained no or few macrophages and were surrounded by smooth muscle actin (SMA)-positive, endothelium-like cells. The subcapsular linear cluster corresponded to 5%-85% (mean, 34.0%) of the nodal circumferential length and was shorter in older patients (p = 0.009). DC rosettes, solitary, or communicating with a cluster, were usually connected to a paracortical lymph sinus. Few differences were found between nodes with or without metastasis, but DC cluster sometimes contained abundant macrophages in cancer metastasis patients. The subcapsular DC cluster is not known in the rodent model, in which the subcapsular sinus is filled with macrophages. This quite different, even complementary, distribution suggests no, or less, cooperation between DCs and macrophages in humans.

Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence.

PURPOSE: Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence. METHODS: One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time. RESULTS: ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05). CONCLUSIONS: The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

[Esophageal Injury Treated with a Covered Expandable Metallic Stent].

We report a case of iatrogenic esophageal injury treated with a covered expandable metallic stent after thoracoscopic chest drainage. A 70-year-old man who had stricture of the esophagus after endoscopic submucosal dissection underwent balloon dilation. Chest computed tomography revealed esophageal rupture. Initially, continuous intra-esophageal drainage was carried out, however, due to the development of mediastinitis with enlarged abscess around the descending aorta and the left pneumothorax, thoracoscopic chest drainage was performed. Since direct closure was thought to be in appropriate, an intra-esophageal approach was chosen and a covered expandable metallic stent was mounted under fluorography on the next day. After the treatment, the patient was able to eat, and was able to discharge 42 days later. Intra-esophageal covered expandable metallic stent can be an alternative treatment for esophageal rupture.

[Metastatic Lung Tumor Diagnosed as Primary Lung Cancer due to its Accompanying Lesion Mimicking Atypical Adenomatous Hyperplasia by Intraoperative Needle Biopsy Findings;Report of a Case].

We reported a case of metastatic lung tumor, which was suspected as being a primary lung cancer because of its accompanying lesion mimicking atypical adenomatous hyperplasia(AAH) based on intraoperative needle biopsy findings. AAH is a preinvasive lesion or marginal lesion of primary lung cancer that is not accompanied by metastatic tumor. However, it needs to be distinguished pathologically from secondary changes of inflammation or fibrosis. In our case, the needle biopsy revealed AAH-like pathological findings, which indicates a primary lung cancer, and the standard lobectomy with lymph node dissection was performed, however, the final diagnosis turned out to be metastatic tumor. The rapidly enlarging tumor led to surrounding obstructive pneumonitis, which may have caused pathological changes mimicking AAH findings. In the case of obstructive pneumonitis, we must be careful to diagnose AAH, in addition to decisions about the surgical procedure especially when based on frozen section diagnosis.

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.

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.

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.

En Bloc Resection of a Primary Tumor and Lymph Nodes in Non-Small-Cell Lung Cancer.

PURPOSE: We established a novel surgical procedure for resectable non-small-cell lung cancer (NSCLC), which involves resection of the affected lobe and regional lymph nodes without separation, namely en bloc surgery. We introduced the technical details and early and late outcomes by comparing them with those of conventional surgery. METHODS: We retrospectively analyzed patients who underwent lobectomy with hilar and mediastinal lymph node dissection for stages I-III NSCLC. A propensity score-matched analysis was performed based on demographic variables. RESULTS: Propensity score-matching yielded 317 pairs. En bloc surgery was not associated with a longer operation time, a higher amount of intraoperative bleeding, or a higher frequency of postoperative complications. The number of resected lymph nodes (P = 0.277) and frequency of N upstaging (P = 0.587) did not differ between the groups. However, en bloc surgery was associated with higher overall survival in comparison to conventional surgery (P = 0.012). According to a stratification analysis, the survival advantage of en bloc surgery over conventional surgery was remarkable in pathological N-positive disease (P = 0.005), whereas it disappeared in pathological N-negative disease (P = 0.147). CONCLUSION: En bloc surgery is feasible and can be performed in patients with possible N-positive NSCLC.

SF6 is a useful expander for post-pneumonectomy syndrome in the long-term course: a case report.

BACKGROUND: Post-pneumonectomy syndrome (PPS) is a rare but serious condition that can occur after pneumonectomy. It is characterized by a mediastinal shift towards the vacated hemithorax, which can potentially lead to respiratory failure. The management of PPS poses a clinical challenge, especially in the context of the limited availability of certain therapeutic devices due to regulatory restrictions in Japan. CASE PRESENTATION: A 36-year-old female with stage IB non-small cell lung cancer underwent left pneumonectomy. Approximately 2 years later, she developed dyspnea. After consulting with our hospital, subsequent imaging revealed an extreme mediastinal shift causing bronchial obstruction. Emergency thoracotomy and subsequent sulfur hexafluoride (SF6) injections were successfully used to manage her condition. Over the course of follow-up, the interval between SF6 injections was extended from 3 to 11 months, indicating an improvement in the intrathoracic condition. CONCLUSIONS: This case illustrates the efficacy of SF6 gas in treating PPS and in reducing the frequency of medical interventions. SF6 gas administration is safe and effective for the treatment of patients with PPS.