No survival benefit of primary tumor resection for non-small cell lung cancer patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with pleural dissemination are generally contraindicated for surgery. This study aimed to investigate the survival benefits of primary tumor resection for NSCLC patients with unexpectedly detected pleural disseminated nodules during thoracotomy in the era of targeted therapy. METHODS: Of the 4984 patients with NSCLC who underwent surgery without induction therapy between 2000 and 2021, we retrospectively evaluated 90 (1.8%) patients with unexpectedly detected pleural disseminated nodule. Survival analyses were performed with Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: Among the evaluated patients, 58 were male, the median age was 67, and 77 (86%) were diagnosed with adenocarcinoma. Exploratory thoracotomy was performed in 21 (23%), and primary tumor resection was performed in 69 (77%) patients, including pneumonectomy in four, lobectomy in 39, and sublobar resection in 26. Epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement were detected in 33 (37%) and 4 (4%) cases, respectively. Among them, 31 patients received targeted therapy. The overall survival (OS) was not significantly different between patients with primary tumor resection and exploratory thoracotomy (5-year OS rate: 30.2% vs. 27.8%, p = 0.81). Multivariable analysis revealed that sex (p = 0.02) and targeted therapy (p < 0.01) were independent prognostic factors for OS. Survival outcomes in patients who received targeted therapy were significantly better regardless of primary tumor resection. CONCLUSIONS: Primary tumor resection might not affect the survival in NSCLC patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Usefulness of final transection of the proximal pulmonary artery in robotic left upper lobectomy.

OBJECTIVES: The pulmonary artery runs around the left upper bronchus, which poses the risk of blood vessel injury when cutting in the blind spot of the bronchus. During robotic surgery, the robotic arm holds the tissue under constant tension; therefore, even if the pulmonary artery is left for final transection, it is not injured by unexpected tension. In this study, we examined the usefulness of final transection of the proximal pulmonary artery in robotic left upper lobectomy. METHODS: This retrospective single-institution study evaluated patients who had undergone robotic lung resection. Of the 453 robotic lung resections performed at our institution between 2017 and 2022, 49 patients who had undergone left upper lobectomy were evaluated. Patients who had undergone bronchial transection followed by pulmonary artery transection were assigned to the group, bronchus prior transection (BT group, n = 38), and those who had undergone pulmonary artery transection followed by bronchial transection were assigned to the group, pulmonary artery prior transection (AT group, n = 11). Patient characteristics and perioperative outcomes were compared between the groups. RESULTS: The groups did not differ significantly in age, sex, smoking history, tumour size, complication rates or 30-day mortality. The BT group inclined to shorter operative times and lesser blood loss. No active intraoperative bleeding occurred in the BT group. However, the AT group had 2 cases of intraoperative pulmonary artery bleeding, one of which required urgent conversion to thoracotomy. CONCLUSIONS: Final transection of the proximal pulmonary artery is a novel and effective surgical technique for robotic left upper lobectomy.

Significance of preoperative exercise oxygen desaturation in lung cancer with interstitial lung disease.

OBJECTIVES: Evaluating the diffusing capacity for carbon monoxide (DLco) is crucial for patients with lung cancer and interstitial lung disease. However, the clinical significance of assessing exercise oxygen desaturation (EOD) remains unclear. METHODS: We retrospectively analysed 186 consecutive patients with interstitial lung disease who underwent lobectomy for non-small-cell lung cancer. EOD was assessed using the two-flight test (TFT), with TFT positivity defined as ≥5% SpO2 reduction. We investigated the impact of EOD and predicted postoperative (ppo)%DLco on postoperative complications and prognosis. RESULTS: A total of 106 (57%) patients were identified as TFT-positive, and 58 (31%) patients had ppo% DLco < 30%. Pulmonary complications were significantly more prevalent in TFT-positive patients than in TFT-negative patients (52% vs 19%, P < 0.001), and multivariable analysis revealed that TFT-positivity was an independent risk factor (odds ratio 3.46, 95% confidence interval 1.70-7.07, P < 0.001), whereas ppo%DLco was not (P = 0.09). In terms of long-term outcomes, both TFT positivity and ppo%DLco < 30% independently predicted overall survival. We divided the patients into 4 groups based on TFT positivity and ppo%DLco status. TFT-positive patients with ppo%DLco < 30% exhibited the significantly lowest 5-year overall survival among the 4 groups: ppo%DLco ≥ 30% and TFT-negative, 54.2%; ppo%DLco < 30% and TFT-negative, 68.8%; ppo%DLco ≥ 30% and TFT-positive, 38.1%; and ppo%DLco < 30% and TFT-positive, 16.7% (P = 0.001). CONCLUSIONS: Incorporating EOD evaluation was useful for predicting postoperative complications and survival outcomes in patients with lung cancer and interstitial lung disease.

Prognostic significance of preoperative exercise tolerance in patients with early-stage lung cancer.

OBJECTIVE: To investigate the influence of simple preoperative exercise tests as prognostic factors for early-stage lung cancer. METHODS: This single-institution retrospective study included consecutive patients who underwent pulmonary resection for stage 0 to I lung cancer between April 2017 and December 2019. Before surgery, 7 metabolic equivalents of task in the double Master 2-step test were loaded into the exercise echocardiogram. The relationship between prognosis and exercise stress test results in terms of availability, symptoms, and saturation of percutaneous oxygen was investigated. RESULTS: This study included 862 patients with pathological stage 0 to I lung cancer. Among the 862 patients, 673 patients (78.1%) who were able to complete 7 metabolic equivalents of task exercise for 3 minutes without assistance were classified into the complete group. The 5-year survival of the complete group was significantly better than that of the incomplete group. Multivariable analysis revealed that age (hazard ratio, 1.06; P = .008), male sex (hazard ratio, 2.23; P = .011), carcinoembryonic antigen level >5 ng/mL (hazard ratio, 2.33; P = .011), and inability to complete 7 metabolic equivalents of task exercise (hazard ratio, 3.90; P < .001) were the prognostic factors. Patients in the older group who had the ability to complete exercise had a better prognosis than those in the younger group without the ability (P = .003). CONCLUSIONS: Preoperative exercise ability is a prognostic factor for early-stage lung cancer. Patients who can tolerate an exercise load of 7 metabolic equivalents of task, even if they are aged 70 years or older, have a better prognosis than patients younger than age 70 years without exercise tolerance.

Oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA lung adenocarcinoma with radiologically pure-solid appearance.

OBJECTIVES: We evaluated the clinicopathological and oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA radiological pure-solid lung adenocarcinoma and compared them with those of a ground-glass opacity component. METHODS: Between 2008 and 2020, data from 1014 surgically resected clinical stage 0-IA epidermal growth factor receptor-mutated lung adenocarcinomas were evaluated. Oncological outcomes were assessed using multivariable analysis. Overall survival was estimated using Kaplan-Meier analysis and the log-rank test. The cumulative incidence of recurrence was estimated using the Gray's test. RESULTS: Of these, 233 (23%) were radiologically pure-solid tumors, which demonstrated a higher proportion of nodal metastasis, micropapillary component, spread through alveolar space, and Ex19 subtype compared with those of tumors with ground-glass opacity (P < .001). Multivariable analysis revealed that the presence of ground-glass opacity was an independently significant factor for overall survival (P = .037) and cumulative incidence of recurrence (P < .001). In cases where the oncological outcomes were stratified by the presence of ground-glass opacity component, the 5-year overall survival was excellent at more than 90% in tumors with ground-glass opacity despite clinical-T categories (P = .2044); however, tumor size significantly affected survival only in pure-solid tumors (T1a, 100%; T1b, 77.7%; T1c, 68.5%; P = .0056). Furthermore, the cumulative incidence of recurrence was low in tumors with ground-glass opacity despite the clinical-T categories, whereas tumor size significantly affected the cumulative incidence of recurrence only in pure-solid tumors (5-year cumulative incidence of recurrence: T1a-b, 18.9%; T1c, 41.3%; P < .001). CONCLUSIONS: Oncologic behavior and prognosis of radiologically pure-solid tumors were significantly poorer than those of tumors with ground-glass opacity among patients with epidermal growth factor receptor-mutated early-stage lung adenocarcinoma. These findings imply distinct tumorigenesis based on the presence of ground-glass opacity, even in tumors with epidermal growth factor receptor mutations.

CO2 Utilization via Direct Aqueous Carbonation of Synthesized Concrete Fines under Atmospheric Pressure.

Mineral carbonation using alkaline wastes is an attractive approach to CO2 utilization. Owing to the difference between waste CO2 and feedstock CO2, developing CO2 utilization technologies without CO2 purification and pressurization is a promising concept. This study investigated a potential method for CO2 utilization via direct aqueous carbonation of synthesized concrete fines under atmospheric pressure and low CO2 concentration. The carbonation reaction with different solid-liquid ratios and different concentrations of introduced CO2 was examined in detail. Under basic conditions, a CO2 uptake of 0.19 g-CO2/g-concrete fines demonstrated that direct aqueous carbonation of concrete fines under atmospheric pressure and low CO2 concentration is effective. The CaCO3 concentration, degree of carbonation, and reaction mechanism were clarified. Furthermore, characterization of the carbonated products was used to evaluate ways of utilizing the carbonated products.

Non-small cell lung carcinoma with diffuse coexpression of thyroid transcription factor-1 and ΔNp63/p40.

Here, we present a case of non-small cell lung carcinoma (NSCLC) with widespread and strong nuclear immunopositivity for both thyroid transcription factor-1 (TTF-1) and ΔNp63/p40 (p40). Double immunofluorescence for TTF-1 and p40 showed coexpression of both markers in the tumor cells. Furthermore, PTEN (pHis123Asp) and TP53 (pVal272Leu) mutations were identified as possible mitogenic driver mutations by next-generation sequencing. To the best of our knowledge, this is the first case of NSCLC harboring concurrent PTEN and TP53 mutations with widespread and strong coexpression of TTF-1 and p40, which has been confirmed in the resected specimen, and only the second documented case of NSCLC with TTF-1 and p40 diffuse coexpression in the carcinoma cells from the same individual. Our case illustrates the possibility that poorly differentiated NSCLCs with widespread and strong nuclear positivity for TTF-1 and p40 may be an underrecognized and new entity.

Differential gene expression profile between cord blood progenitor-derived and adult progenitor-derived human mast cells.

In order to better understand the mechanisms governing the display of mast cell characteristics in human mast cells (MCs), such as cord blood (CB)-derived cultured mast cells, peripheral blood (PB)-derived cultured MCs, and differentiated adult-lung cultured MCs, we examined the transcriptomes of these three types MCs using oligonucleotide microarray (GeneChip) and hierarchical clustering analysis. The expression profile of CB-derived MCs substantially differed from those of PB- and lung-derived MCs. In CB-derived MCs, we identified 132 up-regulated transcripts, such as MARCKS, KRT1, TIMP2, SERPINA1, and TLR2, and 428 down-regulated transcripts, such as LTBP3, CDC42BPA, DDO, DICER1, and FCER1A. Moreover, using RT-PCR and FACS analysis, we confirmed the expression of TLR2, which plays an important role in innate immunity, in CB-derived MCs but not in PB-derived MCs. In addition, it was observed that CB-derived MCs uniquely release histamine and CCL1, which are produced by human MCs but not by human monocytes, in response to peptidoglycan (PGN), although it had been controversy issue whether CB-derived MCs could, in fact, induce degranulation in response to PGN. These results indicated that in innate immunity MCs derived from neonatal hemopoietic cells might have unique functions compared to their adult counterparts because of different gene profiles.

Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcepsilonRI.

Rodent mast cells (MCs) are reported to play a pivotal role in both innate and adaptive immunity. However, there is so far no evidence that human MCs are involved in innate immunity. We found that a functional Toll-like receptor 4 (TLR4) was expressed on human MCs when it was up-regulated by interferon gamma (IFN-gamma). To systematically explore how human MCs modulate the immune system following TLR4-mediated activation and FcepsilonRI aggregation, we used high-density oligonucleotide probe arrays (GeneChip) to compare the lipopolysaccharide (LPS)-induced gene expression profile with the IgE/anti-IgE-mediated profile in MCs. Both a shared core response, and LPS- or anti-IgE-specific programs of gene expression were observed in MCs. Furthermore, MCs exhibited an antiviral response gene program in response to IFN-gamma, and LPS sustained that expression. Compared with the LPS-stimulated gene expression profile of human peripheral blood mononuclear cells, LPS-stimulated MCs specifically induced a subset of genes that included a Th2 cytokine and chemokines that recruit Th2 cells and eosinophils. These results reveal that human MCs express tailored pathogen- and antigen-specific immune responses and that human MCs may play important roles in innate and adaptive immunity.