Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

In the last two decades, robotic-assisted thoracoscopic surgery (RATS) has gained popularity as a minimally invasive surgical (MIS) alternative to multi- and uniportal video-assisted thoracoscopic surgery (VATS). With this approach, the surgeon obviates the known drawbacks of conventional MIS, such as the reduced in-depth perception, hand-eye coordination, and freedom of motion of the instruments. Previous studies have shown that a robotic approach for operable lung cancer has treatment outcomes comparable to other MIS techniques such as multi-and uniportal VATS, but with less blood loss, a lower conversion rate to open surgery, better lymph node dissection rates, and improved ergonomics for the surgeon. The thoracic surgeon of the future is expected to perform more complex procedures. More patients will enter a multimodal treatment scheme making surgery more difficult due to severe inflammation. Furthermore, due to lung cancer screening programs, the number of patients presenting with operable smaller lung nodules in the periphery of the lung will increase. This, combined with the fact that segmentectomy is becoming an increasingly popular treatment for small peripheral lung lesions, indicates that the future thoracic surgeons need to have profound knowledge of segmental resections. New imaging techniques will help them to locate these lesions and to achieve a complete oncologic resection. Current robotic techniques exist to help the thoracic surgeon overcome these challenges. In this review, an update of the latest MIS approaches and nodule detection techniques will be given.

Angiogenesis significantly influences the carcinogenesis of thymic epithelial tumors (TET). Both thymomas and thymic carcinoma (TC) overexpress VEGF-A and VEGFR-1 and -2. This review aims to provide an appraisal of the use of anti-angiogenics in the treatment of TET. The literature research identified 16 studies that were deemed eligible for further analysis. Seven studies assessed the clinical efficacy of sunitinib and five studies the use of apatinib and/or anlotinib. The multicenter Japanese phase II REMORA trial investigated the efficacy of lenvatinib, which is a multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The objective response rate was 38% (25.6–52%), which is the highest documented in TET that progressed after first-line chemotherapy. Anti-angiogenic agents may be useful in the treatment of TET, which are not amenable to curative treatment. Their toxicity profile seems to be acceptable. However, angiogenesis inhibitors do not appear to have a major influence on either thymomas or TC, although multikinase inhibitors may have some effect on TC. The current evidence suggests that the most active agent is lenvatinib, whereas sunitinib could be proposed as an acceptable second-line therapy for TC. Further research concerning the combination of immune checkpoint inhibitors with anti-angiogenic drugs is warranted.

For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement.

Pulmonary ossifications have often been regarded as rare, post-mortem findings without any clinical significance. We have investigated the occurrence of pulmonary ossifications in patients undergoing thoracic procedures, and how this may affect the differential diagnosis of solitary pulmonary nodules. In addition, we have performed a literature search on the occurrence and possible pathogenesis of these ossifications. From January 2008 until August 2019, we identified pulmonary ossifications in 34 patients who underwent elective pulmonary surgery. Pre-operative imaging was unable to differentiate these ossifications from solid tumors. A definitive diagnosis was made by an experienced pathologist (VS, ML). The PubMed database was researched in December 2019 with the search terms “pulmonary ossifications”; “heterotopic ossifications”; and “solitary pulmonary nodule”. In total, 27 patients were male, with a mean age of 63 ± 12 years (age 41 to 82 on diagnosis). All lesions were identified on thoracic CT and marked for resection by a multidisciplinary team. A total of 17 patients were diagnosed with malignancy concurrent with ossifications. There was a clear predilection for the right lower lobe (12 cases, 35.3%) and most ossifications had a nodular form (70.6%). We could not identify a clear association with any other pathology, either cancerous or non-cancerous in origin. Oncologic or pulmonary comorbidities did not influence patient survival. Pulmonary ossifications are not as seldom as thought and are not just a curiosity finding by pathologists. These formations may be mistaken for a malignant space-occupying lesion, both pre-and perioperatively, as they are indistinguishable in imaging. We propose these ossifications as an underestimated addition to the differential diagnosis of a solitary pulmonary nodule.

Lung ischemia–reperfusion injury (LIRI) remains a major contributor to perioperative morbidity and mortality in thoracic surgery, especially for lung transplantations, where it is one of the principal drivers of primary graft dysfunction (PGD). Although substantial advances have been made in surgical technique, donor management, and perioperative care, LIRI continues to pose a significant clinical challenge. Mechanistically, LIRI reflects a combined pathology of oxidative stress, endothelial and glycocalyx disruption, innate immune activation, mitochondrial dysfunction, and regulated cell death, resulting in loss of alveolar–capillary barrier integrity and gas exchange failure. Current management is phase-specific and multimodal, spanning donor care and preservation, controlled reperfusion and lung-protective ventilation, and pharmacological treatments. Treatment candidates that target oxidative stress and inflammatory cascades (e.g., antioxidants, complement and adenosine pathways, mesenchymal stromal cell products, and dipeptidyl-peptidase-4 inhibition) show promise, yet translation into a clinical scenario remains difficult. Increasing evidence supports endothelial-preserving and mitochondria-sparing strategies, rigorous perioperative bundles, and biomarker-guided trials to move from pathophysiology to practice. Ultimately, addressing LIRI requires an integrated, multidisciplinary approach that spans surgical, anesthetic, and pharmacologic domains, with the goal of improving both early outcomes and long-term graft survival in lung transplant patients.