Takahiro Karasaki

Objectives: Intraoperative mobile CT (iCT) and virtual-assisted lung mapping (VAL-MAP) are used to localize pulmonary nodules that are difficult to palpate during minimally invasive surgery. Because these techniques differ in workflow structure and timing of image acquisition, their operative time and radiation exposure may differ. We aimed to describe workflow characteristics and radiation exposure associated with newly implemented iCT and to contextualize these findings against our established VAL-MAP practice. Methods: We retrospectively reviewed 50 consecutive patients who underwent thoracoscopic wedge resection with localization between January 2024 and December 2025. Twenty-four underwent iCT-guided localization using an O-arm system, and 26 underwent VAL-MAP with bronchoscopic dye marking followed by post-mapping CT. Technique selection was based on device availability and surgeon discretion. CT dose metrics and time components related to localization were analyzed. Results: Median CT-related dose-length product (DLP) was higher in the iCT group, primarily due to high-definition scans. When performed in standard mode with a limited scan frequency, iCT radiation exposure approximated that of post-VAL-MAP CT. Preparation CT after lateral positioning reduced repeat scans and iCT-related interruption time. Anesthesia and operative times were shorter in the VAL-MAP cohort, reflecting localization outside the operating room. Overall procedural burden appeared modestly different. Conclusion: Our single-center retrospective study quantified the total procedural time for VAL-MAP and iCT, finding modest differences in time and radiation exposure. These real-world data aid institutions considering these localization strategies, but do not establish superiority. Definitive comparative conclusions require future prospective evaluations controlling for nodule characteristics and cost.

Introduction: The role of metastasis‐directed therapy in urothelial carcinoma remains uncertain, particularly in the immune checkpoint inhibitor era. We report a case of solitary pulmonary metastasis that developed after a favorable response to pembrolizumab and was managed with metastasectomy. Case Presentation: A 65‐year‐old man with ureteral carcinoma underwent radical nephroureterectomy followed by adjuvant gemcitabine plus carboplatin. Three months later, a solitary pulmonary metastasis was detected and pembrolizumab was initiated. After initial enlargement, the lesion regressed and achieved a partial response after 13 cycles, followed by slight regrowth after 18 cycles, consistent with oligoprogression. Video‐assisted thoracoscopic metastasectomy was performed 14 months after pembrolizumab initiation. Pembrolizumab was continued for 1 year postoperatively, with no recurrence observed 17 months after surgery. Conclusion: This case suggests that metastasis‐directed therapy may be a reasonable option for carefully selected patients with oligoprogressive urothelial carcinoma during immune checkpoint inhibitor therapy.

Limited understanding of the biological processes that govern metastatic dissemination hinders its prevention and treatment ¹ . Here, using 501 longitudinally collected primary and metastatic tumour samples from 24 patients with non-small cell lung cancer (NSCLC) enrolled in the TRACERx lung study and PEACE autopsy programme, we infer tumour evolution from diagnosis to death. With DNA-sequencing data encompassing 70% of the metastases that were radiologically detected before death and paired multi-region sampled primary tumours, we show that the genomes of metastases diverge markedly from those of their ancestral primary tumour, with additional driver alterations and genome doubling events occurring after metastatic dissemination. In 62.5% of patients, multiple primary tumour subclones disseminated, each founding a distinct metastasis. These metastases served as sources of onward spread: more than half of the metastases sampled were seeded by other metastases. The duration that metastases existed in situ influenced their likelihood of seeding further metastases. Most metastatic migrations started and ended in the same anatomical cavity. The few subclones that exited the thorax to seed metastases disseminated widely and were enriched for somatic copy-number alterations, suggesting that chromosomal instability may facilitate extrathoracic spread. This spatial and temporal evolutionary analysis sheds light on the extent of metastatic diversity and seeding in advanced NSCLC—which tends to be underestimated in single metastasis biopsies—and identifies genomic and clinical mediators of metastatic progression.

Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data. Intratumoral methylation distance quantifies intratumor DNA methylation heterogeneity. M_R/M_N classifies genes based on the rate of hypermethylation at regulatory (M_R) versus nonregulatory (M_N) CpGs to identify driver genes exhibiting recurrent functional hypermethylation. We identified DNA methylation-linked dosage compensation of essential genes co-amplified with neighboring oncogenes. We propose two complementary mechanisms that converge for copy number alteration-affected chromatin to undergo the epigenetic equivalent of an allosteric activity transition. Hypermethylated driver genes under positive selection may open avenues for therapeutic stratification of patients.

Both single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumour development, fuelling clonal evolution. However, accurate estimation of clone-specific copy numbers from bulk DNA-sequencing data is challenging. Here we present allele-specific phylogenetic analysis of copy number alterations (ALPACA), a method to infer SNV and SCNA coevolution by leveraging phylogenetic trees reconstructed from multi-sample bulk tumour sequencing data using SNV frequencies. ALPACA estimates the SCNA evolution of simulated tumours with a higher accuracy than current state-of-the-art methods^1–4. ALPACA uncovers loss-of-heterozygosity and amplification events in minor clones that may be missed using standard approaches and reveals the temporal order of somatic alterations. Analysing clone-specific copy numbers in TRACERx421 lung tumours^5,6, we find evidence of increased chromosomal instability in metastasis-seeding clones and enrichment for losses affecting tumour suppressor genes and amplification affecting CCND1. Furthermore, we identify increased SCNA rates in both tumours with polyclonal metastatic dissemination and tumours with extrathoracic metastases, and an association between higher clone copy number diversity and reduced disease-free survival in patients with lung cancer.

Background and Objective: Bronchopleural fistula (BPF) is a serious postoperative complication associated with surgical mortality following thoracic surgery. To reduce the risk of mortality by BPF, reinforcement by bronchial stump coverage is suggested for patients with a high risk of developing BPF. In the present study, we aimed to review the techniques for covering the bronchial stump after lung resection, focusing on the methods using free pericardial fat graft and pedicled thymic flap that can be performed via a minimally invasive approach. Methods: A literature search using the PubMed database was performed. The search process was originally conducted in December 2024 and in February 2025 upon revision. Data on the incidence, timing, and risks of BPF after lung resection were collected. The studies describing the number of patients who underwent bronchial stump coverage via a minimally invasive approach were included during the manual review. The studies focusing on postoperative retention of engrafted tissues were also included. Key Content and Findings: Three original articles described the number of patients who underwent bronchial stump coverage using free pericardial fat grafts and pedicled thymic flaps via a minimally invasive approach. Pedicled intercostal muscle and pericardial flaps can also be harvested via minimally invasive approaches, although these techniques were only described in case reports. The retention rate of the engrafted tissue after bronchial stump coverage has recently been investigated by several researchers. Reports using free pericardial fat pats showed that grafts were detected on the computed tomography (CT) scans at more than 2 months postoperatively. Pedicled thymic flaps with a secured blood flow reportedly retain longer, as compared to free pericardial fat grafts, although the graft retention rate may vary depending on how tissue retention was defined. Conclusions: Bronchial stump coverage using free pericardial fat pads or pedicled thymic grafts, which can be obtained through a minimally invasive approach and remain adjacent to the bronchial stump for >2 months, may be proactively utilized for patients at risk of developing BPF.

Introduction With the global trend of aging populations, the number of nonagenarians diagnosed with malignancies, including lung cancer, is increasing. Despite advancements in minimally invasive surgical techniques, lung resection for nonagenarians remains rare due to concerns regarding comorbidities and surgical risks. This study evaluates the surgical outcomes of lung resection in nonagenarians and introduces a holistic assessment approach to optimize patient care. Methods A retrospective review of surgical records from January 2011 to December 2022 identified seven nonagenarians who underwent lung resection under 3-port video-assisted thoracoscopic surgery (VATS). Patient characteristics, surgical details, and postoperative outcomes were analyzed. To holistically evaluate each patient, multifaceted surgical tolerance and prognostic factors were summarized and visualized in a radar plot. Results The study cohort consisted of four males and three females aged 90 to 96 years. Wedge resection was performed in six patients, and one patient underwent lobectomy. Mediastinal lymph node dissection was not performed. The median duration of chest tube insertion was two days, and 86% of patients were discharged within one week. Postoperative complications were minimal, with one case of delirium and no occurrences of pneumonia. All patients were discharged in stable condition without deterioration of their activities of daily living. The median overall survival was 4.1 years. One patient succumbed to lung cancer progression, while the remaining patients exhibited favorable long-term survival without recurrence, including one patient whose lung tumor was a metastasis from colorectal cancer. As depicted in the radar plots, all patients had at least one risk factor other than their age. Conclusion Lung resection under a minimally invasive approach is feasible for carefully selected nonagenarians, yielding favorable short- and long-term outcomes. Because super-elderlies likely harbor multiple comorbidities, a holistic assessment of each patient is important for personalized patient care.

Background and Objective: Bronchopleural fistula (BPF) is a rare postoperative complication following lung resection but with high mortality. BPF treatment and prevention remain a major challenge in thoracic surgery. This review focuses on the current management of BPF with a special focus on the techniques and evidence of bronchial stump covering to mitigate the morbidity and mortality of BPF. Methods: A literature search was performed during the month of December 2024 using the PubMed database. Search terms included “bronchial stump” and “coverage” or “reinforcement”. The time frame of the search included 1990–2024, and the language inclusion was English. In addition to the 101 literature flagged by the initial screening, the citations used in these articles were also used in this review. Key Content and Findings: To minimize the fistula and separate the bronchial stump and adjacent vessels, various tissues, including pedicled intercostal muscle, pericardium, thymus, or pericardial fat, are used to cover the bronchial stump after lung resection. Mounting evidence suggests that bronchial stump coverage also effectively reduces the incidence of BPF. One prospective randomized trial demonstrated significantly lower BPF rates with pedicled intercostal muscle flaps than no coverage. Retrospective studies provide mixed results influenced by the high-risk nature of patients receiving bronchial stump coverage. Pedicled muscle flaps, including intercostal muscle and latissimus dorsi muscle, can be easily harvested under open thoracotomy, whilst free pericardial fat pad and pedicled thymus can be harvested under a minimally invasive approach. Conclusions: To reduce surgical morbidity and mortality and to improve patient care, it is essential to revisit the management of postoperative BPF and understand the characteristics of each bronchial stump coverage technique. Bronchial stump coverage, especially using grafts that can be harvested under a minimally invasive approach, may be proactively applied for patients at risk of BPF.