Background: Recent trials, including JCOG0802/WJOG4607L and CALGB140503, have confirmed the oncological adequacy of segmentectomy for early-stage non-small-cell lung cancer (NSCLC). This shift emphasizes the preservation of pulmonary function and minimal invasiveness. Robot-assisted thoracic surgery (RATS) offers enhanced anatomical precision and potentially improves segmentectomy outcomes. Methods: We reviewed the current evidence comparing sublobar resection and lobectomy for early-stage NSCLC, focusing on RATS segmentectomy. Clinical trials, perioperative and long-term outcomes, technical innovations, and patient selection criteria were analyzed. Comparative data among RATS, video-assisted thoracoscopic surgery (VATS), and open approaches were synthesized, including the emerging roles of AI and 3D imaging. Results: Segmentectomy yields survival outcomes equivalent or superior to lobectomy for stage IA peripheral NSCLC ≤2 cm, with better pulmonary function despite higher locoregional recurrence. RATS enhances visualization, dexterity, and ergonomics, thereby enabling precise dissection and lymph node assessment. Compared to VATS and open surgery, RATS shows lower conversion rates, reduced pain, and comparable oncological control. Innovations, such as indocyanine green imaging, 3D modeling, and AI-guided navigation, support margin accuracy and personalized care. Conclusions: Segmentectomy has redefined the surgical standards for early-stage NSCLC. RATS maximizes the minimally invasive benefits by combining oncological safety and functional preservation. Its technical precision facilitates complex resections and integration with digital planning tools to advance personalized thoracic surgery. RATS represents the next evolution of minimally invasive thoracic surgery, redefining the balance between oncological safety and functional preservation in early-stage NSCLC.

OBJECTIVE: Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. MATERIALS AND METHODS: The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy. RESULTS: FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671nm laser at a dose of 10J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis. CONCLUSION: Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.

There has been an increase in the use of image-guided technology to facilitate minimally invasive therapy. The next generation of minimally invasive therapy is focused on advancement and translation of novel image-guided technologies in therapeutic interventions, including surgery, interventional pulmonology, radiation therapy, and interventional laser therapy. To establish the efficacy of different minimally invasive therapies, we have developed a hybrid operating room, known as the guided therapeutics operating room (GTx OR) at the Toronto General Hospital. The GTx OR is equipped with multi-modality image-guidance systems, which features a dual source-dual energy computed tomography (CT) scanner, a robotic cone-beam CT (CBCT)/fluoroscopy, high-performance endobronchial ultrasound system, endoscopic surgery system, near-infrared (NIR) fluorescence imaging system, and navigation tracking systems. The novel multimodality image-guidance systems allow physicians to quickly, and accurately image patients while they are on the operating table. This yield improved outcomes since physicians are able to use image guidance during their procedures, and carry out innovative multi-modality therapeutics. Multiple preclinical translational studies pertaining to innovative minimally invasive technology is being developed in our guided therapeutics laboratory (GTx Lab). The GTx Lab is equipped with similar technology, and multimodality image-guidance systems as the GTx OR, and acts as an appropriate platform for translation of research into human clinical trials. Through the GTx Lab, we are able to perform basic research, such as the development of image-guided technologies, preclinical model testing, as well as preclinical imaging, and then translate that research into the GTx OR. This OR allows for the utilization of new technologies in cancer therapy, including molecular imaging, and other innovative imaging modalities, and therefore enables a better quality of life for patients, both during and after the procedure. In this article, we describe capabilities of the GTx systems, and discuss the first-in-human technologies used, and evaluated in GTx OR.

症例は53歳男性．検診の胸部X線写真にて異常陰影を指摘．胸部単純CTにて，下後縦隔，胸椎近傍に38×25×50 mm大の腫瘤を指摘．PET-CTにて，同部位に一致して，集積亢進を認めた（SUV max 3.37）．画像上，神経原性腫瘍が疑われ，診断，治療目的で手術の方針となった．胸腔鏡下縦隔腫瘍摘出術施行．後縦隔に血管の豊富な腫瘍を認め，止血に難渋したが，切除した．迅速組織診では明らかな悪性所見を認めず，永久病理組織検査でヒアリン血管型Castleman病の診断となった．現在追加治療なく外来にて観察中である．縦隔腫瘍は主にCTやMRIで診断がなされるが，近年付加的画像診断として，FDG-PETが用いられている．PET-CTにて異常集積を認めた，Castleman病を経験したので，画像的特徴に関して，文献的考察を加えて報告する．

非常に稀な肺原発淡明細胞腫の1切除例を経験した．症例は57歳女性．胸部打撲精査で施行した胸部X線写真にて，右下肺野に結節影を指摘された．胸部CTにて右中葉に辺縁整で，比較的造影効果の高い14mm大の結節を認め，転移性肺腫瘍または良性腫瘍を疑わせる所見であった．FDG-PETでは右中葉の結節影を含めて，全身に明らかな異常集積を認めなかった．診断および治療目的で胸腔鏡下右肺中葉部分切除術を施行した．腫瘍は，19×13×10mm大，白色調，充実性腫瘍であり，病理所見では，細胞異型は乏しく，壊死や核分裂像は明らかではなく，淡明で比較的豊かな細胞質を有する明細胞が充実性に増殖していた．免疫組織化学的染色ではHMB45（＋），vimentin（＋），TTF-1（－），SP-A（－），AE1/3（－），CAM 5.2（－）であった．以上より，肺原発淡明細胞腫と診断された．

本研究の目的は，肺癌、悪性胸膜中皮腫などの胸部悪性腫瘍に対し、癌幹細胞のC D44をターゲットとした、「CD44抗体-IR700結合体」による光免疫治療（NIR-PIT）を確立することである。研究期間内に、「CD44抗体-IR700結合体」を利用したNIR-PITを確立し， NIR-PITスコープを開発する。また、In vitro, In vivoレベルで治療効果を検証し、「アブスコパル効果」を肺癌同所性モデルで検証し、ヒトへの臨床応用を目指す。初年度の目標として、 ①「IR700」特異的なNIR-PITスコープの開発: 細径ファイバースコープを、IR700のレーザー波長で使用できるように調整し、ストレートタイプのレーザーファイバーでより広い範囲にレーザー照射可能なNIR-PITスコープを開発する。 ②細胞株を用いた「CD44抗体-IR700」のがん細胞への集積確認と治療効果の評価（In vitro）: マウスがん細胞株 (マウスCD44(+)肺癌：LL/2 cellマウス/ヒト CD44抗体：IM7マウスCD44(+)中皮腫：AB22) を用い，CD44発現をwestern blotで確認し，CD44陽性株と陰性株を同定する。In Vitro実験では陽性株に「CD44抗体-IR700」を導入後，FACS/蛍光顕微鏡を用い細胞への集積性を確認する。レーザー照射を行い，MTS assayにより壊死細胞の評価を行い、治療効果判定を行うことを目標とした。