Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma.

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer-specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern-based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer-specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern-based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.

Evaluation of radiofrequency identification tag accuracy using bronchoscopy with fluoroscopy and virtual navigation guidance before segmentectomy.

BACKGROUND: The use of sublobar resection has increased with advances in imaging technologies. However, it is difficult for thoracic surgeons to identify small lung tumours intraoperatively. Radiofrequency identification (RFID) lung-marking systems are useful for overcoming this difficulty; however, accurate placement is essential for maximum effectiveness. METHODS: We retrospectively reviewed patients who underwent RFID tag placement via fluoroscopic bronchoscopy under virtual bronchoscopic navigation (VBN) guidance before our institution's sublobar resection of lung lesions. Thirty-one patients with 31 lung lesions underwent RFID lung-marking with fluoroscopic bronchoscopy under VBN guidance. RESULTS: Of the 31 procedures, 26 tags were placed within 10 mm of the target site, 2 were placed more than 10 mm away from the target site, and 3 were placed in a different area from the target bronchus. No clinical complications were associated with RFID tag placement, such as pneumothorax or bleeding. The contribution of the RFID lung-marking system to surgery was high, particularly when the RFID tag was placed at the target site and tumour was located in the intermediate hilar zone. CONCLUSIONS: An RFID tag can be placed near the target site using fluoroscopic bronchoscopy in combination with VBN guidance. RFID tag placement under fluoroscopic bronchoscopy with VBN guidance is useful for certain segmentectomies.

Synthesis and activity of 3-oxo-α-ionone analogs as male attractants for the solanaceous fruit fly, Bactrocera latifrons (Diptera: Tephritidae).

A series of 3-oxygenated α-ionone analogs have been developed as highly specific male lures for the solanaceous fruit fly Bactrocera latifrons, a pest of solanaceous fruits. We compared the attractant and phagostimulant activities of analogs with or without (i) unsaturations at the 4,5- and/or 7,8-positions and (ii) oxygen moieties at the 3- and/or 9-positions of the ionone molecule. Since naturally occurring vomifoliol (V2) was found to induce a highly potent phagostimulant activity in B. latifrons males, related analogs including dehydrovomifoliol (V1), 6-hydroxy-α-ionone (U1), and 6-hydroxy-α-ionol (U2) were synthesized to evaluate their attractant and phagostimulant activities. Synthetic V1, V2, U1, and U2 exhibited low attractant activity, but their phagostimulant activity was relatively high. Optical isomers of 3-oxo-7,8-dihydro-α-ionone (P3) and V1 were prepared to examine the stereochemical specificity of attractants. (+)-(6R)-P3 and (+)-(6S)-V1 exhibited the corresponding activities, while their respective antipodal enantiomers were found entirely inactive.

V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma.

V-domain Ig-containing suppressor of T-cell activation (VISTA) is an immune checkpoint gene that inhibits anti-tumor immune responses. Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort. VISTA and PD-L1 immunohistochemistry were performed on tissue microarray of immunotherapy-naive pleural mesotheliomas (254 epithelioid, 24 biphasic and 41 sarcomatoid) and ten whole-tissue sections of benign pleura (VISTA only). Percentages of tumor and inflammatory cells with positive staining were assessed. Optimal prognostic cutoff percentages were determined using maximally selected rank statistics. Overall survival was evaluated using Kaplan-Meier methods and Cox proportional hazard analysis. All benign mesothelium expressed VISTA. Eighty-five percent of 319 and 38% of 304 mesotheliomas expressed VISTA and PD-L1 (88% and 33% of epithelioid, 90% and 43% of biphasic, and 42% and 75% of sarcomatoid), respectively. Median VISTA score was significantly higher in epithelioid (50%) (vs. biphasic [20%] and sarcomatoid [0]) (p < 0.001), while median PD-L1 score was significantly higher in sarcomatoid tumors (20%) (vs. biphasic and epithelioid [both 0%]) (p < 0.001). VISTA and PD-L1 were expressed in inflammatory cells in 94% (n = 317) and 24% (n = 303) of mesothelioma, respectively. Optimal prognostic cutoffs for VISTA and PD-L1 were 40% and 30%, respectively. On multivariable analysis, VISTA and PD-L1 expression in mesothelioma were associated with better and worse overall survival (p = 0.001 and p = 0.002), respectively, independent of histology. In a large cohort of mesothelioma, we report frequent expression of VISTA and infrequent expression of PD-L1 with favorable and unfavorable survival correlations, respectively. These findings may explain poor responses to anti-PD-(L)1 immunotherapy and suggest VISTA as a potential novel target in pleural mesothelioma.

A Stepwise Approach for Postlobectomy Bronchopleural Fistula.

Although rare, bronchopleural fistula (BPF) following anatomic lung resection is a serious complication associated with high rates of mortality (25%-71%). Risk factors for BPF include surgical approach, neoadjuvant therapy, diabetes mellitus, and chronic obstructive pulmonary disease. As neoadjuvant treatment is increasingly being administered to patients with locally advanced lung cancer, and as more patients are being diagnosed with lung cancer at an older age-elderly patients present with a higher index of multiple comorbidities-the incidence of BPF among patients undergoing anatomic resection for lung cancer is expected to increase. In this manuscript, we detail risk factors and considerations for BPF and describe a stepwise approach to treat BPF following lobectomy for lung cancer.

Minimally Invasive Lobectomy Is Associated With Lower Noncancer-specific Mortality in Elderly Patients: A Propensity Score Matched Competing Risks Analysis.

OBJECTIVE: To investigate cancer- and noncancer-specific mortality following lobectomy by minimally invasive surgery (MIS) versus open thoracotomy in elderly patients with nonsmall cell lung cancer (NSCLC). BACKGROUND: Two-thirds of patients with NSCLC are ≥65 years of age. As age increases, the risk of competing events, such as noncancer death, also increases. METHODS: Elderly patients (≥65 yrs of age) who have undergone curative-intent lobectomy for stage I-III NSCLC without induction therapy (2002-2013) were included (n=1,303). Of those, 607 patients had undergone MIS and 696 had undergone thoracotomy. Propensity-score matching was performed to identify pairs of thoracotomy and MIS patients with comparable clinical characteristics (eg, year of surgery, comorbidities, and pulmonary function). Association between surgical approach (MIS vs thoracotomy) and lung cancer-specific and noncancer-specific cumulative incidence of death (CID) was analyzed using competing risks approach. RESULTS: Following propensity score matching of patients who had undergone thoracotomy (n=338) versus MIS (n=338), MIS was associated with shorter length of stay (P <0.001), lower noncancer-specific 1-year mortality (P=0.027), and lower noncancer-specific CID (P=0.014) compared with thoracotomy; there was no difference in lung cancer-specific CID between surgical approaches. On multivariable analysis, thoracotomy was a significant risk factor for noncancer-specific death (subhazard ratio 2.45, 95% CI 1.18-5.06, P=0.016) independent of age, sex, and diffusion capacity of the lungs for carbon monoxide. CONCLUSION: In a propensity score-matched cohort, multivariable analysis has indicated that lobectomy performed by MIS is associated with lower incidence of noncancer-specific mortality compared with lobectomy performed by open thoracotomy in elderly patients with NSCLC.

Successful lung lobectomy for a lung cancer following thoracic endovascular aortic repair for a thoracic aortic aneurysm: report of a case.

Lung cancer and a thoracic aortic aneurysm were detected simultaneously in a 79-year-old male patient with diabetes. The aneurysm was first treated by thoracic endovascular aortic repair. A right lower lobectomy was subsequently performed after the blood flow of the bronchial and intercostal arteries was confirmed by computed tomographic angiography. The bronchial stump was covered with an intercostal muscle flap. The patient's postoperative course was uneventful. Thoracic endovascular aortic repair is a useful and less invasive treatment for such cases, but a blood flow evaluation of the aortic branches should be done following this procedure before a lung resection is considered.

Complex segmentectomy for non-palpable small lung cancer adjacent to the incomplete interlobar fissure using radiofrequency identification.

Pulmonary segmentectomy for small non-palpable tumors, such as lung cancer or pulmonary metastasis, is challenging owing to possible insufficient surgical margins. Particularly, extensive segmentectomy beyond the second lobe may be required to obtain a sufficient surgical margin for a tumor adjacent to an incomplete interlobar fissure. Radiofrequency identification (RFID) marking systems have proven beneficial for detecting small lung tumors during surgery. Herein, we present two representative cases of complex segmentectomy (left-side video-assisted thoracoscopic extended S8 + S9 segmentectomy and left-side robot-assisted thoracoscopic extended S1+2 b + c segmentectomy) for small lung cancer adjacent to an incomplete interlobar fissure. Extensive segmentectomy was avoided, and preservation of lung parenchyma was feasible using an RFID system. The patients could undergo segmentectomy safely with a sufficient surgical margin. In conclusion, an RFID system facilitates secure and safe precise segmentectomy while minimizing the resected pulmonary volume.

Saving Lives in Thoracic Surgery: Balancing Oncological Radicality and Functional Preservation, Transitioning from Standard Pneumonectomy to Targeted Sublobar Resection.

This review chronicles the evolution of thoracic surgical interventions, from the standardized pneumonectomy to the precise approach of sublobar resections. It discusses the emergence and acceptance of minimally invasive and robot-assisted surgical techniques, highlighting their impact on improving outcomes beyond cancer and their influence on the surgical management of early-stage lung cancer. Evaluating historical developments alongside present methodologies, this review underscores the critical need for meticulous surgical planning and execution to optimize both oncological radicality and functional preservation. This evolution portrayed not only technical advancements but also a shift in the clinical approach towards tailored, organ-preserving methodologies, culminating in a contemporary framework promoting sublobar resections as the standard for specific patient profiles, signifying a new era of precision in thoracic surgery.

Sublobar resection or lobectomy and postoperative respiratory complications in emphysematous lungs.

OBJECTIVES: Pulmonary resection in patients with severe emphysema may impact postoperative respiratory complications. Low-attenuation areas evaluated using three-dimensional computed tomography to assess emphysematous changes are strongly associated with postoperative respiratory complications. Herein, we investigated the relationship between low-attenuation area, the surgical procedure and resected lung volume, which has not been explored in previous studies. METHODS: We retrospectively evaluated patients with primary or metastatic lung cancer who underwent surgical resection. The low-attenuation area percentage (low-attenuation area/total lung area × 100) and resected lung volume were calculated using three-dimensional computed tomography software, and the relationship with postoperative respiratory complications was analysed. RESULTS: Postoperative respiratory complications occurred in 66 patients (17%) in the total cohort (n = 383). We set the median value of 1.1% as the cut-off value for low-attenuation area percentage to predict postoperative respiratory complications, which occurred in 24% and 10% of patients with low-attenuation area >1.1% and <1.1%, respectively (P < 0.001). Postoperative respiratory complications occurred in approximately one-third of the patients with low-attenuation area >1.1%, whose resected lung volume was ≥15.8% or ≥5 resected subsegments. Multivariable analysis revealed that sublobar resection was associated with a significantly lower risk of postoperative respiratory complications in patients with low-attenuation area >1.1% (odds ratio 0.4, 95% confidence interval 0.183-0.875). CONCLUSIONS: Emphysema is a risk factor for postoperative respiratory complications, and lobectomy is an independent predictive risk factor. Preserving more lung parenchyma may yield better short-term prognoses in patients with emphysematous lungs.

Prognostic significance of immune-cell distribution and tumoral spread through air spaces - Multiplex spatial immunophenotyping analysis.

Objectives: Spread through air spaces (STAS) is a form of lung cancer invasion that extends beyond the tumor edge and is associated with a worse prognosis. Recent advances in immunotherapy highlight the importance of understanding the tumor microenvironment. This study aimed to investigate the prognostic significance of immune-cell distribution in lung cancer, focusing on the association with STAS. Materials and methods: We retrospectively analyzed 283 patients who underwent curative-intent lung resection for primary lung cancer. Multiplex immunofluorescence staining/phenotyping was performed on tissue microarrays to assess the distribution of CD4, CD8, CD20, CD68, and FoxP3 immune cells within the center and tumor edge. We defined the delta-Edge value (Δ) as the difference in the number of immune cells between the tumor edge and center. Recurrence-free probability (RFP) was analyzed using Kaplan-Meier and Cox proportional hazard models. Results: High ΔCD4 and ΔCD8 values were significantly associated with worse RFP. In stage I adenocarcinoma patients, STAS, and high ΔCD8 were independent risk factors for recurrence. Effect modification analysis revealed that high ΔFoxP3 was significantly associated with worse RFP in patients with STAS, but not in those without STAS. Patients with STAS and high Δimmune cell values had the lowest RFP among all groups. Conclusion: Immune-cell distribution, particularly CD4, CD8, and FoxP3, is a crucial prognostic factor in lung cancer. STAS and specific immune cell distribution patterns can be used to further stratify patient prognosis. Understanding these interactions may provide insights into potential therapeutic targets for personalized lung cancer treatment.

Long-term pulmonary repair in rat lungs after sublobar resection: electrocautery versus stapler methods.

OBJECTIVE: We investigated and compared the long-term (6-month) histologic changes in a rat model of sublobar resection created using electrocautery or stapler techniques. METHODS: Nine-week-old male rats were anesthetized and intubated; thoracotomy with sublobar resection was performed in the right middle lobe using electrocautery or stapler techniques. Histological examination was performed at 2, 4, 8, 12, and 24 weeks post-surgery to assess long-term effects on lung tissue repair and morphologic changes. Lung expansion and alveolar epithelial cell proliferation were evaluated by measuring the mean linear intercept and counting the number of alveolar type I and II cells. RESULTS: The electrocautery group showed signs of lung self-repair at the resected area over time, with inflammatory cell infiltration followed by growth of vessels and bronchioles. Mesothelial cells covered the resected area by 2 weeks; elastic fibers gradually connected from both sides by 24 weeks. Lung expansion, measured by mean linear intercept, was initially small below the electrocautery resection area at 2 weeks but recovered from 4 to 24 weeks. The stapler group showed persistently small mean linear intercept over time. In the electrocautery group, the number of alveolar type II cells was higher just below the resection than in other areas from 2 to 24 weeks, followed by alveolar type I cells (4 to 24 weeks). The stapler group showed a transient alveolar type II cell increase at 2 weeks. CONCLUSIONS: Compared to the stapler technique, electrocautery may provide advantages for postoperative lung repair by promoting lung expansion and alveolar epithelial cell proliferation.

Improving intraoperative diagnosis of spread through air spaces: A cryo-embedding-medium inflation method for frozen section analysis.

Objective: Accurate intraoperative diagnosis of spread through air spaces (STAS), a known poor prognostic factor in lung cancer, is crucial for guiding surgical decision-making during sublobar resections. This study aimed to evaluate the diagnostic sensitivity of STAS using frozen section (FS) slides prepared with the cryo-embedding medium inflation technique. Methods: In this prospective study at Shinshu University Hospital, 99 patients undergoing lung resection for tumors <3 cm in size were included, a total of 114 lesions. FS slides were prepared with injecting diluted cryo-embedding medium into the lung parenchyma of resected specimens. The diagnostic performance of these FS slides for STAS detection was evaluated by comparing FS-STAS results with the gold-standard STAS status. Results: The incidence of STAS, determined by the gold standard, was 43 (38%) of 114 lesions, including 31 (37%) of 84 primary lung cancers and 12 (40%) of 30 metastatic lung tumors. The sensitivity, specificity, positive and negative predictive values, and accuracy of FS slides for STAS detection were 81%, 89%, 81%, 89%, and 86%, respectively. Specifically, in primary lung cancers, these values were 90%, 89%, 82%, 94%, and 89%, respectively. Regarding metastatic lung tumors, the corresponding values were 58%, 89%, 78%, 76%, and 77%, respectively. Conclusions: Our adapted cryo-embedding medium inflation method has demonstrated enhanced sensitivity in detecting STAS on FS slides, providing results similar to the gold-standard STAS detection. Compared with historical benchmarks, this technique could show excellent performance and be readily incorporated into clinical practice without requiring additional resources beyond those used for standard FS analysis.

Segmentectomy-oriented anatomical model for enhanced precision surgery of the left upper lobe.

Objective: To optimize surgical outcomes and minimize complications in complex segmentectomy of the left upper lobe, we investigated the topographical anatomy of the left upper lobe and developed a segmentectomy-oriented anatomical model. Methods: A state-of-the-art 3-dimensional computed tomography workstation was used to visualize the intersegmental planes and associated veins to categorize the anatomical patterns influencing surgical procedures during left upper lobe segmentectomy. This included the central vein affecting S1+2 (apicoposterior segment) segmentectomy, the transverse S3 (anterior segment) affecting S3 segmentectomy, and other venous branching patterns in 395 patients who underwent thoracic surgery at our institution. Results: The central vein was observed in 32% of the patients, necessitating access from the interlobar area after segmental artery and bronchus division. Transverse S3 incidence was 27%, revealing that only one-third of the patients required complete left upper lobe transection between S4 and S3 during S3 segmentectomy. A significant negative correlation was observed between the presence of transverse S3 and the central vein (<10% of patients with the central vein had transverse S3 and vice versa). In 6% of patients, the lingular segmental veins partially or entirely drained into the inferior pulmonary vein, potentially causing excessive or insufficient resection during surgery. Conclusions: This study offers valuable insights into the topographic anatomy of the left upper lobe and presents a segmentectomy-oriented anatomical model for complex segmentectomies. Our approach enables a more precise and individualized surgical planning for patients undergoing segmentectomy based on their unique anatomy, which could thereby lead to improved patient outcomes.

Personalized Medicine in Thoracic Surgery: The Role and Future of Robotic-Assisted Techniques.

The advent of robotic-assisted thoracic surgery (RATS) has revolutionized the field of thoracic surgery, offering a new paradigm for personalized, precision, and individualized medicine [...].

Port Placement Variations for Robotic Lung Resection: Focusing on Their History, Conventional Look-Up-View and Horizontal Open-Thoracotomy-View Techniques, and More.

This is a narrative review that summarizes the variations in approaches and port placements used for performing robotic lung resections on the da Vinci Surgical Platforms. Currently, the four-arm, look-up-view method, in which the intrathoracic cranial side is viewed from the caudal side, is considered the mainstream approach worldwide. Several variations were devised from this conventional technique, including the so-called horizontal open-thoracotomy-view techniques in which the intrathoracic craniocaudal axis is aligned with the horizontal direction of the console monitor, and fewer port and incision techniques. In September 2022, 166 reports were surveyed using a PubMed English literature search, and this review finally included 30 reports describing the approaches. We categorized the variations into four-phase groups considering advent histories: (I) early era, three-arm technique with utility incisions; (II) four-arm, total port technique without robotic staplers; (III) four-arm technique using robotic staplers; (IV) maximizing the functional features of the Xi, significant alterations in viewing directions, and reducing ports, including the ultimate uniport technique. To comprehensibly visualize these variations for practical use, we created elaborate illustrations based on the literature. The familiarity of thoracic surgeons with the variations and characteristics allows them to choose the optimal procedure that best suits each patient and their preferences.

Harnessing 3D-CT Simulation and Planning for Enhanced Precision Surgery: A Review of Applications and Advancements in Lung Cancer Treatment.

The clinical application of three-dimensional computed tomography (3D-CT) technology has rapidly expanded in the last decade and has been applied to lung cancer surgery. Two consecutive reports of large-scale prospective clinical trials from Japan and the United States have brought a paradigm shift in lung cancer surgery and may have led to a rapid increase in sublobar lung resections. Sublobar resection, especially segmentectomy, requires a more precise understanding of the anatomy than lobectomy, and preoperative 3D simulation and intraoperative navigation support it. The latest 3D simulation software packages are user-friendly. Therefore, in this narrative review, we focus on recent attempts to apply 3D imaging technologies, particularly in the sublobar resection of the lung, and review respective research and outcomes. Improvements in CT accuracy and the use of 3D technology have advanced lung segmental anatomy. Clinical applications have enabled the safe execution of complex sublobar resection through a minimally invasive approach, such as video-assisted thoracoscopic surgery and robotic surgery. However, currently, many facilities still render 3D images on two-dimensional monitors for usage. In the future, it will be challenging to further spread and advance intraoperative navigation through the application of 3D output technologies such as extended reality.

Clinical features of recurrent spontaneous pneumomediastinum.

Background: Spontaneous pneumomediastinum recurrence is rare, and its clinical presentation is unclear. We investigated the clinical features of and predisposing factors for spontaneous pneumomediastinum recurrence. Methods: We retrospectively investigated 30 consecutive patients treated for new-onset spontaneous pneumomediastinum at Shinshu Ueda Medical Center between 2012 and 2021. We evaluated the patient background characteristics, trigger activity, radiological findings, and clinical course of spontaneous pneumomediastinum, including those of recurrent cases. Predisposing factors for spontaneous pneumomediastinum recurrence were evaluated by comparing patients with and without recurrence. Results: Most patients were male (87%). The median age of the patients was 16 years (range, 12-26 years). Among the 30 patients, five experienced at least one recurrence of spontaneous pneumomediastinum. All recurrences occurred within 1 year after new-onset spontaneous pneumomediastinum. Clinical presentations associated with spontaneous pneumomediastinum recurrence, including vital signs, laboratory data, length of hospital stay, and radiological extent of spontaneous pneumomediastinum, were similar to or less aggressive than those associated with new-onset spontaneous pneumomediastinum. Patients with recurrence were more likely to have a medical history of preexisting lung diseases, such as asthma, than those without recurrence (60% vs. 8%; P=0.022). Only one of five patients with recurrence had trigger activity at spontaneous pneumomediastinum onset (20%); however, 60% of patients without recurrence had trigger activity (P=0.15). Conclusions: Spontaneous pneumomediastinum recurrence may have a similar or less aggressive clinical presentation than new-onset spontaneous pneumomediastinum. The presence of preexisting lung diseases may increase the risk of spontaneous pneumomediastinum recurrence.

Anatomical resection for right B3 downwards-shifting malformation.

The right B3 downwards-shifting malformation is rare. This malformation often leads to the following complications: abnormal pulmonary arteries that accompany the downward-displaced B3, and complete fusion of the upper and middle lobes into one lobe, with no horizonal fissure. When performing pulmonary anatomical resection in the right upper or middle lobes in patients with this malformation, careful preoperative planning and surgical technique are required, with which the surgeon should be familiar. Herein, we present the anatomical features necessary for anatomical resection of the right B3 downwards-shifting malformation based on our technical experiences with anatomic segmentectomy and lobectomy techniques.