The crosstalk between lung cancer and the bone marrow niche fuels emergency myelopoiesis.

Modest response rates to immunotherapy observed in advanced lung cancer patients underscore the need to identify reliable biomarkers and targets, enhancing both treatment decision-making and efficacy. Factors such as PD-L1 expression, tumor mutation burden, and a 'hot' tumor microenvironment with heightened effector T cell infiltration have consistently been associated with positive responses. In contrast, the predictive role of the abundantly present tumor-infiltrating myeloid cell (TIMs) fraction remains somewhat uncertain, partly explained by their towering variety in terms of ontogeny, phenotype, location, and function. Nevertheless, numerous preclinical and clinical studies established a clear link between lung cancer progression and alterations in intra- and extramedullary hematopoiesis, leading to emergency myelopoiesis at the expense of megakaryocyte/erythroid and lymphoid differentiation. These observations affirm that a continuous crosstalk between solid cancers such as lung cancer and the bone marrow niche (BMN) must take place. However, the BMN, encompassing hematopoietic stem and progenitor cells, differentiated immune and stromal cells, remains inadequately explored in solid cancer patients. Subsequently, no clear consensus has been reached on the exact breadth of tumor installed hematopoiesis perturbing cues nor their predictive power for immunotherapy. As the current era of single-cell omics is reshaping our understanding of the hematopoietic process and the subcluster landscape of lung TIMs, we aim to present an updated overview of the hierarchical differentiation process of TIMs within the BMN of solid cancer bearing subjects. Our comprehensive overview underscores that lung cancer should be regarded as a systemic disease in which the cues governing the lung tumor-BMN crosstalk might bolster the definition of new biomarkers and druggable targets, potentially mitigating the high attrition rate of leading immunotherapies for NSCLC.

Lung transplantation following controlled hypothermic storage with a portable lung preservation device: first multicenter European experience.

Introduction: Compared with traditional static ice storage, controlled hypothermic storage (CHS) at 4-10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device. Methods: A prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers. The LUNGguard device was used for CHS. The preservation details, total ischemic time, and early postoperative outcomes are described. The data are presented as median (range: minimum-maximum) values. Results: A total of 36 patients underwent LTx (i.e., 33 bilateral, 2 single LTx, and 1 lobar). The median age was 61 (15-68) years; 58% of the patients were male; 28% of the transplantations had high-urgency status; and 22% were indicated as donation after circulatory death. In 47% of the patients, extracorporeal membrane oxygenation (ECMO) was used for perioperative support. The indications for using the CHS device were overnight bridging (n = 26), remote procurement (n = 4), rescue allocation (n = 2), logistics (n = 2), feasibility (n = 1), and extended-criteria donor (n = 1). The CHS temperature was 6.5°C (3.7°C-9.3°C). The preservation times were 11 h 18 (2 h 42-17 h 9) and 13 h 40 (4 h 5-19 h 36) for the first and second implanted lungs, respectively, whereas the total ischemic times were 13 h 38 (4 h 51-19 h 44) and 15 h 41 (5 h 54-22 h 48), respectively. The primary graft dysfunction grade 3 (PGD3) incidence rates were 33.3% within 72 h and 2.8% at 72 h. Intensive care unit stay was 8 (4-62) days, and the hospital stay was 28 (13-87) days. At the last follow-up [139 (7-446) days], three patients were still hospitalized. One patient died on postoperative day 7 due to ECMO failure. In-hospital Clavien-Dindo complications of 3b were observed in six (17%) patients, and 4a in seven (19%). Conclusion: CHS seems safe and feasible despite the high-risk recipient and donor profiles, as well as extended preservation times. PGD3 at 72 h was observed in 2.8% of the patients. This technology could postpone LTx to daytime working hours. Larger cohorts and longer-term outcomes are required to confirm these observations.

Uniportal versus multiportal video-assisted thoracoscopic surgery for spontaneous pneumothorax.

BACKGROUND: Multiportal video-assisted thoracic surgery (mVATS) is the standard approach for the surgical treatment of spontaneous pneumothorax. However, uniportal VATS (uVATS) has emerged as an alternative aiming to minimize surgical morbidity. This study aims to strengthen the evidence on the safety and efficiency of uVATS compared to mVATS. METHODS: From January 2004 to December 2020, records of patients who had undergone surgical treatment for primary or secondary spontaneous pneumothorax were evaluated for eligibility. Patients who had undergone pleurectomy combined with bullectomy or apical wedge resection via uVATS or mVATS were included. Surgical characteristics and postoperative data were compared between patients who had undergone surgery via uVATS or mVATS. Univariable and multivariable analyses were performed to determine whether the surgical approach was associated with any complication (primary outcome), major complications (i.e., Clavien-Dindo ≥ 3), recurrence, prolonged hospitalization or prolonged chest drainage duration (secondary outcomes). RESULTS: A total of 212 patients were enrolled. Patients treated via uVATS (n = 71) and mVATS (n = 141) were significantly different in pneumothorax type (secondary spontaneous; uVATS: 54 [76%], mVATS: 79 [56%]; p = 0.004). No significant differences were observed in (major) complications and recurrence rates between both groups. Multivariable analyses revealed that the surgical approach was no significant predictor for the primary or secondary outcomes. CONCLUSIONS: This study indicates that uVATS is non-inferior to mVATS in the surgical treatment of spontaneous pneumothorax regarding safety and efficiency, and thus the uVATS approach has the potential for further improvements in the perioperative surgical care for spontaneous pneumothorax.

The use of intravenous indocyanine green in minimally invasive segmental lung resections: a systematic review.

Background: To identify intersegmental planes (ISPs) in video/robot-assisted thoracoscopic segmentectomies, indocyanine green (ICG) is commonly used. The aim of this systematic review is to evaluate the efficacy of intravenous ICG in the identification of ISP. Methods: A systematic search was performed. Studies evaluating patients who underwent a video/robot-assisted thoracoscopic segmentectomy using intravenous ICG were included. The primary outcome measure was the frequency and percentage of patients in whom the ISP was adequately visualized. Secondary outcomes encompassed the ICG dose, time to visualization, time to maximum ICG visualization, time to disappearance of ICG effect and adverse reactions to ICG. Results: Eighteen studies were included for systematic review, enrolling a total of 1,090 patients. Irrespective of the injected dose, intravenous ICG identified the ISP in 94% of the cases (range, 30-100%). Overall, there was a considerable amount of heterogeneity regarding the injected dose of ICG (range, 5-25 mg or 0.05-0.5 mg/kg). The mean time before first effect of ICG was visible ranged from 10 to 40 seconds. The mean total time of ICG visibility ranged from 90 to 140 seconds after a bolus injection and was 170 seconds after continuous infusion. No adverse reactions were reported. Conclusions: After administration of intravenous ICG, visualization of the ISP is successful in up to 94% of cases, even after administration of a low dose (0.05 mg/kg) of ICG. The use of intravenous ICG is safe with no reported adverse effects in the immediate peri-operative period.

Unraveling the spectrum of inflammatory myofibroblastic tumors in the lung: A comprehensive case series highlighting endobronchial, pleural, and lung parenchymal tumors.

Objectives: Diverse cases of inflammatory myofibroblastic tumors (IMTs) in the lung (pleural, endobronchial, and parenchymal) are presented while discussing the (preoperative) diagnostic challenges and treatment modalities. Other objectives include emphasizing the significance of gene rearrangements and highlighting the multidisciplinary approach in addressing IMTs. Methods: Four cases of IMT in the lung are presented, including a young adolescent girl with an ETV6-neurotrophic tyrosine receptor kinase 3 (NTRK3) gene rearrangement, a 5-year-old boy with challenging preoperative diagnosis, and 2 middle-aged women with respectively pleural and endobronchial tumors with one peribronchial relapse. Results: The cases demonstrate the diverse clinical presentations and diagnostic complexities associated with IMT in the lung. Surgical resection remains the primary treatment modality, with complete resection leading to a cure in most patients. Unfortunately, aggressive relapse can occur, as in our last case of an endobronchial tumor. Frozen section may confirm the presence of malignant cells perioperatively and impact further treatment. The presence of gene rearrangements, such as ETV6-NTRK3, suggests potential therapeutic implications. Conclusions: Early detection and complete surgical removal of IMT are crucial for effective treatment. Identifying gene rearrangements such as ETV6-NTRK3 holds promise for targeted therapies. Diagnostic challenges, including the controversy of biopsies and preoperative evaluations, underscore the importance of a multidisciplinary approach. Anatomopathological recognition of IMT stays demanding. Close surveillance is necessary due to potential relapse, whereas frozen section perioperatively can help further treatment. This case series emphasizes the diagnostic challenges and therapeutic considerations for IMT in the lung.