CT-Guided Dual-Fluorescent Marking to Localize Small Pulmonary Nodules for Robotic Sublobar Resection: Technical Note from 84 Consecutive Cases.

Pulmonary nodules present a unique challenge for radiologists which includes the detection of malignancy and identification of benign disease, recommending the appropriate procedures to avoid unnecessary thoracotomy, and ensuring that excessive radiation from follow-up computed tomography (CT) examinations is kept to a minimum. Although seasoned radiologists can use an approach based on their extensive experience, in this era of evidence-based medicine, guidelines have been established that include both radiologic and clinical factors in an integrated fashion. Such guidelines have been developed by the Fleischner Society, first in 2005, for the management of small pulmonary nodules detected on CT scans, and then, in 2013, for the management of sub-solid nodules [1]. For incidentally detected solitary nodules, these guidelines integrate elements as individual risk factors (via pre-test probability), with lesion size, growth rate, and morphology, based on imaging characteristics. Relevant risk factors to consider in the evaluation of pulmonary nodules are smoking history and patient age. Patients with a substantial smoking history and over 40 years of age are defined as high-risk patients, whereas low-risk patients are those with a negligible smoking history and no other known risk factors, and who are below 40 years of age. Based on the Fleischner Society recommendation [1], lesions less than 4 mm do not require any further invasive or non-invasive measures or evaluations. However, lesions with a diameter of more than 8mm should be evaluated with either follow-up CT scans, including dynamic, contrast-enhanced scans, positron emission tomography (PET)-CT, and biopsy. For lesions that fall between the 4 mm and 8 mm size, CT follow-up with a limited number of scans is recommended. Sub-solid nodules are often found during screening studies or incidentally on CT scans. They are characterized by their appearance as rounded areas of increased attenuation, and a homogeneous or heterogeneous texture. Sub-solid nodules can be subdivided according to their composition: non-solid lesions that consist of ground-glass opacity only; and part solid lesions that contain both ground-glass and soft tissue elements. Sub-solid nodules can regress, persist, or grow. Small persistent non-solid nodules are often atypical adenomatous hypoplasia (AAH) and focal fibrosis, whereas non-solid and part-solid nodules that increase in size typically indicate malignancy, which can include adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma, as well as lympho-proliferative disease. How these lesions develop has not been entirely elucidated as yet, but it seems that a small percentage of ground-glass opacities (AAH) develop into larger lesions that can eventually comprise solid components due to invasion and alveolar collapse [2]. In any case, radiologically, an increase in lesion density, growth, or the development of solid portions are all indicative of malignancy. CT analysis and surveillance of sub-solid nodules is the modality of choice for the identification of malignant lesions. The primary factor is nodule size. While lesions less than 5 mm in diameter are usually AAHs, lesions greater than 15 mm is size are malignant, and are typically MIAs and invasive adenocarcinomas. Generally, a diameter of more than 8 mm is indicative of malignancy. Another important indicator of malignancy is lesion growth. The growth of the lesion may affect either the ground-glass or the solid components, or both. Volume doubling times of AIS and MIAs are much longer, compared to invasive adenocarcinomas and squamous cell lesions. Morphologically, the presence of lobulated borders, air bronchograms and bubble-like lucencies, and the development of solid portions in pure ground-glass abnormalities are all indicative of malignancy. Lesion morphology is closely related to prognosis. Nodules with an increasing percentage of solid components represent a poorer prognosis, but, for patients with pure ground-glass abnormalities or those with only a small area of a solid component, the survival rate after lesion resection is 100%. The Fleischner Society management guidelines [2] for sub-solid lesions recommend that part solid nodules, especially those that persist or grow in size, mandate further evaluation and monitoring, and typically, require surgical resection. Smaller lesions, with a negligible area of solid components, can be managed with follow-up CT scans.

To explore the natural history of pulmonary subsolid nodules (SSNs) with different pathological types by deep learning-assisted nodule segmentation. Between June 2012 and June 2019, 95 resected SSNs with preoperative long-term follow-up were enrolled in this retrospective study. SSN detection and segmentation were performed on preoperative follow-up CTs using the deep learning-based Dr. Wise system. SSNs were categorized into invasive adenocarcinoma (IAC, n = 47) and non-IAC (n = 48) groups; according to the interval change during the preoperative follow-up, SSNs were divided into growth (n = 68), nongrowth (n = 22), and new emergence (n = 5) groups. We analyzed the cumulative percentages and pattern of SSN growth and identified significant factors for IAC diagnosis and SSN growth. The mean preoperative follow-up was 42.1 ± 17.0 months. More SSNs showed growth or new emergence in the IAC than in the non-IAC group (89.4% vs. 64.6%, p = 0.009). Volume doubling time was non-significantly shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days, p = 0.077). Median mass doubling time was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). Lobulated sign (p = 0.002) and SSN mass (p = 0.004) were significant factors for differentiating IACs. IACs showed significantly higher cumulative growth percentages than non-IACs in the first 70 months of follow-up. The growth pattern of SSNs may conform to the exponential model. The initial volume (p = 0.042) was a predictor for SSN growth. IACs appearing as SSNs showed an indolent course. The mean growth rate was larger for IACs than for non-IACs. SSNs with larger initial volume are more likely to grow. • Invasive adenocarcinomas (IACs) appearing as subsolid nodules (SSNs), with a mean volume doubling time (VDT) of 1436.0 ± 1188.2 days and median mass doubling time (MDT) of 821.7 days, showed an indolent course. • The VDT was shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days), but the difference was not significant (p = 0.077). The median MDT was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). • SSNs with lobulated sign and larger mass (> 390.5 mg) may very likely be IACs. SSNs with larger initial volume are more likely to grow.

Robotic-assisted thoracic surgery (RATS) has become a promising treatment for pulmonary neoplasms. DuringRATS, intraoperative ultrasonography can act as an "alternative finger" to "touch" and locate lesions, especially pulmonarynodules. This study was aimed to investigate the efficacy of intraoperative ultrasonographic localization during da Vinci RATSprocedures. Patients with pulmonary nodules were randomly divided into an Experimental Group andControl Group in which nodules were respectively located using intraoperative ultrasonography or by the surgeon's anatomicknowledge. The success rates and relevant localization factors were compared between the groups and analyzed to concludethe efficacy of intraoperative ultrasonography. Additionally, the intraoperative ultrasonography learning curve was analyzedto evaluate each surgeon's ability to independently perform intraoperative ultrasonography. Thirty-four patients wereincluded in the study (n = 17/group). Respectively, the Experimental Group and Control Group comprised 41.2% and 58.9%women (p= 0.937), and had average ages of 55.5 and 55.8 years. In the Experimental group, ultrasonographic localization formixed ground-glass nodules with CT values of -500 to -100 Hounsfield units had an efficacy of 87.5%. By contrast, the localizationefficacy in Control Group was 20.0% (p=0.032).A single surgeon without prior experience performed intraoperative ultrasonography in 20 cases, and the latter 10 procedures required significantly less time relative to the former 10 procedures(p=0.000). During RATS, the use of intraoperative ultrasonography as an "alternative finger" to "touch" and findthe accurate location of pulmonary nodules, especially mixed ground-glass nodules, is warranted.

BackgroundSmall and ground glass pulmonary nodules pose a surgical and diagnostic challenge, with an increase in identification expected with the roll-out of lung cancer screening in Australia. Accurate preoperative localisation of small pulmonary nodules can be a useful adjunct to lung resection in nodules that are not palpable. Various methods have been trialled including methylene blue dye injection and hook-wire placement; however, these are limited by dye diffusion, wire dislodgement, and patient discomfort. CT-guided insertion of a microcoil is a technique of localisation that provides a stable and visible marker on X-ray, improving intraoperative identification. This study reports an Australian institutional experience with this technique and evaluates its safety and efficacy.MethodsA retrospective review of all patients undergoing CT-guided pulmonary microcoil localisation followed by video-assisted thoracoscopic surgery (VATS) was conducted at the Alfred Hospital, Melbourne. A case series of 19 patients from 2021 - 2025 was identified and data on technical success, complications, operative outcomes, and pathology were collected.ResultsThe mean patient age was 63.5 years, with a slight male predominance (n=11, 57.8%). Indications for lung resection included pulmonary metastasectomy (n=12, 63.2%) and primary lung adenocarcinoma (n=7, 36.8%). The indication for microcoil guidance was a deep nodule in 36.8% (n=7) of cases and in 63.1% (n=12) of cases an impalpable nodule due to small size or ground glass appearance. The technical success of microcoil placement was 94.3% (n=18), with one displaced microcoil early in the series. No pneumothorax requiring intervention occurred and no major radiological complications from microcoil placement seen in the series. All lesions were successfully resected, with clear histologic margins and no major surgical complications. The mean chest drain duration was 3.4 days and mean hospital stay 4.6 days.ConclusionsCT-guided pulmonary microcoil insertion is a safe, reliable, and reproducible technique for intraoperative identification of small or impalpable pulmonary nodules. It addresses some of the limitations of previous localisation methods and demonstrates excellent outcomes in an Australian setting. Future developments may include indocyanine green-coated microcoils for fluorescence guidance during robotic-assisted thoracic surgery.

Video-assisted thoracic surgery (VATS) and robotically assisted surgery are used increasingly for minimally invasive diagnostic and therapeutic resection of pulmonary nodules. Unsuccessful localization of small, impalpable, or deep pulmonary nodules can necessitate conversion from VATS to open thoracotomy. Preoperative localization techniques performed by radiologists have improved the success rates of VATS resection for small and subsolid nodules. Any center at which VATS diagnostic resection of indeterminate pulmonary nodules is performed should be supported by radiologists who offer preoperative nodule localization. Many techniques have been described, including image-guided injection of radioisotopes and radiopaque liquids and placement of metallic wires, coils, and fiducial markers. These markers enable the surgeon to visualize the position of an impalpable nodule intraoperatively. This article provides details on how to perform each percutaneous localization technique, and a group of national experts with established nodule localization programs describe their preferred approaches. Special reference is made to equipment required, optimization of marker placement, prevention of technique-specific complications, and postprocedural treatment. This comprehensive unbiased review provides valuable information for those who are considering implementation or optimization of a nodule localization program according to workflow patterns, surgeon preference, and institutional resources in a particular center. ©RSNA, 2019.

An Effective Malignancy Prediction Model for Incidentally Detected Pulmonary Subsolid Nodules Based on Current and Prior CT Scans

BackgroundRecent studies have shown that near-infrared (NIR) fluorescence imaging using Indocyanine green (ICG) may improve the efficiency of sentinel lymph node biopsy (SLNB). This study aimed to assess the effectiveness of the combination of ICG and methylene blue (MB) in breast cancer patients undergoing SLNB.Patients and methodWe evaluated ICG plus MB (ICG + MB) identification effectiveness with MB alone using retrospective analysis. From 2016 to 2020, we collected data on 300 eligible breast cancer patients who got SLNB treatment in our institution by ICG + MB or MB alone. By comparing the distribution of clinicopathological characteristics, the detection rate of sentinel lymph nodes (SLNs) and metastatic SLNs, as well as the total number of SLNs in the two groups, we were able to assess the imaging efficiency.ResultsFluorescence imaging allowed 131 out of 136 patients in the ICG + MB group to find SLNs. ICG + MB group and MB group had detection rates of 98.5% and 91.5% (P = 0.007, χ2 = 7.352), respectively. Besides, the ICG + MB approach was able to produce improved recognition outcomes. What’s more, compared with the MB group, the ICG + MB group can identify more lymph nodes (LNs) (3.1 to 2.6, P = 0.000, t = 4.447). Additionally, in the ICG + MB group, ICG could identify more LNs than MB (3.1 vs 2.6, P = 0.004, t = 2.884).ConclusionICG has high detection effectiveness for SLNs, and when paired with MB, the detection efficiency can be increased even further. Furthermore, the ICG + MB tracing mode does not involve radioisotopes, which has a lot of promise for clinical use and can take the place of conventional standard detection methods.

PurposeTo examine the effect of lung volume on the size and volume of pulmonary subsolid nodules (SSNs) measured on CT.Materials and MethodsA total of 42 SSNs from 31 patients were included. CT examination was first performed at total lung capacity (TLC), and a section containing the nodule was additionally scanned at tidal volume (TV). The diameter and volume of each SSN, as well as the cross-sectional lung area containing the nodule, were measured. The significance of the changes in measurements between TLC and TV within the same individuals was evaluated.ResultsThe lung area and the diameter and volume of SSNs decreased significantly at TV by 12.7 cm2, 0.5 mm, and 46.4 mm3 on average, respectively (p < 0.001), compared to those at TLC. Changes in lung area between TV and TLC were positively correlated with the change in SSN diameter (p = 0.027) and volume (p = 0.014). However, after correction (by considering the change in lung area), the changes in SSN diameter (p = 0.124) and volume (p = 0.062) were not significantly different.ConclusionSSN size and volume can be significantly affected by lung volume during CT scans of the same individuals.

We hypothesized that semi-automatic diameter measurements would improve the accuracy and reproducibility in discriminating preinvasive lesions and minimally invasive adenocarcinomas from invasive pulmonary adenocarcinomas appearing as subsolid nodules (SSNs) and increase the reproducibility in classifying SSNs. Two readers independently performed semi-automatic and manual measurements of the diameters of 102 SSNs and their solid portions. Diagnostic performance in predicting invasive adenocarcinoma based on diameters was tested using logistic regression analysis with subsequent receiver operating characteristic curves. Inter- and intrareader reproducibilities of diagnosis and SSN classification according to Fleischner's guidelines were investigated for each measurement method using Cohen's κ statistics. Semi-automatic effective diameter measurements were superior to manual average diameters for the diagnosis of invasive adenocarcinoma (AUC, 0.905-0.923 for semi-automatic measurement and 0.833-0.864 for manual measurement; p<0.05). Reproducibility of diagnosis between the readers also improved with semi-automatic measurement (κ=0.924 for semi-automatic measurement and 0.690 for manual measurement, p=0.012). Inter-reader SSN classification reproducibility was significantly higher with semi-automatic measurement (κ=0.861 for semi-automatic measurement and 0.683 for manual measurement, p=0.022). Semi-automatic effective diameter measurement offers an opportunity to improve diagnostic accuracy and reproducibility as well as the classification reproducibility of SSNs. • Semi-automatic effective diameter measurement improves the diagnostic accuracy for pulmonary subsolid nodules. • Semi-automatic measurement increases the inter-reader agreement on the diagnosis for subsolid nodules. • Semi-automatic measurement augments the inter-reader reproducibility for the classification of subsolid nodules.

BackgroundClinical management of subsolid nodules (SSNs) is defined by the suspicion of tumor invasiveness. We sought to develop an artificial intelligent (AI) algorithm for invasiveness assessment of lung adenocarcinoma manifesting as radiological SSNs. We investigated the performance of this algorithm in classification of SSNs related to invasiveness.MethodsA retrospective chest computed tomography (CT) dataset of 1,589 SSNs was constructed to develop (85%) and internally test (15%) the proposed AI diagnostic tool, SSNet. Diagnostic performance was evaluated in the hold-out test set and was further tested in an external cohort of 102 SSNs. Three thoracic surgeons and three radiologists were required to evaluate the invasiveness of SSNs on both test datasets to investigate the clinical utility of the proposed SSNet.ResultsIn the differentiation of invasive adenocarcinoma (IA), SSNet achieved a similar area under the curve [AUC; 0.914, 95% confidence interval (CI): 0.813–0.987] with that of the 6 doctors (0.900, 95% CI: 0.867–0.922). When interpreting with the assistance of SSNet, the sensitivity of junior doctors, specificity of senior doctor, and their accuracy were significantly improved. In the external test, SSNet (AUC: 0.949, 95% CI: 0.884–1.000) achieved a better AUC than doctors (AUC: 0.883, 95% CI: 0.826–0.939) whose AUC increased (AUC: 0.908, 95% CI: 0.847–0.982) with SSNet assistance. In the histological subtype classifications, SSNet achieved better performance than practicing doctors. The AUCs of doctors were significantly improved with the assistance of SSNet in both 4-category and 3-category classifications to 0.836 (95% CI: 0.811–0.862) and 0.852 (95% CI: 0.825–0.882), respectively.ConclusionsThe AI diagnostic system achieved non-inferior performance to doctors, and will potentially improve diagnostic performance and efficiency in SSN evaluation.

Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study

This retrospective single-center study evaluated and compared the short-term outcomes of robot-assisted thoracic surgery (RATS) segmentectomy with those of conventional segmentectomy performed via thoracotomy or video-assisted thoracic surgery (VATS). The primary objective was to assess the safety of RATS segmentectomy. Our findings demonstrated that RATS segmentectomy was found to be as safe as conventional segmentectomy, with shorter operation times and hospital stays. No significant differences were observed in intraoperative blood loss and rates of surgical complications. However, prolonged postoperative air leaks are a potential concern. Among simple segmentectomy cases, RATS still showed shorter operation time and hospital stay. The longer experience of the surgeons in the RATS group may be a reason for the shorter operation time in this group. Additionally, the use of preoperative transbronchial marking with indocyanine green dye and barium, and intraoperative identification of intersegmental boundaries using intravenously administered indocyanine green dye may contribute to shorter operation time. Further studies are warranted to clarify the long-term oncological outcomes.

To develop and validate a concise prediction model using simple size measures for the discrimination of invasive pulmonary adenocarcinomas (IPAs) among incidentally detected subsolid nodules (SSNs) considered for resection and to compare its diagnostic performance with the Brock model. This retrospective institutional review board-approved study included 427 surgically resected SSNs (121 preinvasive lesions/minimally invasive adenocarcinomas [MIAs] and 306 IPAs) from 407 patients. After stratified random splitting of the study population into the training and validation sets (3:1), a simple logistic model was constructed using nodule size, solid proportion, and type for the differentiation of IPAs. Diagnostic performance of this model was compared with the original and modified Brock models using the DeLong method for area under the receiver-operating characteristic curve (AUC) and McNemar test for diagnostic sensitivity and specificity. Our proposed model had an AUC of 0.859 in the validation set, while the original Brock model showed an AUC of 0.775 (p = 0.035) and the modified Brock model exhibited an AUC of 0.787 (p = 0.006). At equally high specificity of 90%, our proposed model exhibited significantly higher sensitivity (65.8%) than the original and modified Brock models (38.2% and 50.0%; p < 0.001 and 0.008, respectively). Our study results demonstrated that the proposed concise model outperformed both Brock models, demonstrating its potential to be utilized as a specific tool to differentiate IPAs from preinvasive lesions and MIAs, which were considered for resection. External validation studies are warranted for the population with incidentally detected SSNs including small SSNs to confirm our observations. • Size measures provided sufficient information for the risk stratification of surgical candidate incidental subsolid nodules. • Our proposed concise model showed higher diagnostic performance than the Brock model for incidentally detected subsolid nodules. • Our proposed model can specifically differentiate invasive adenocarcinomas among incidentally detected subsolid nodules and reduce overtreatment for indolent subsolid nodules.

Studies like the International Early Lung Cancer Action Program (I-ELCAP) (1) have revolutionized our understanding of early-stage lung cancer and its management. In their recent article (2), Flores and colleagues challenge us with the notion that sublobar resection without mediastinal lymph node sampling may be an adequate treatment for clinical stage IA non-small cell lung cancer (NSCLC). Drawing on the database of the I-ELCAP project (1), they were able to stratify patients into two propensity matched cohorts who received mediastinal lymph node resection (MLNR) and those who did not. A solid statistical and survival analysis methodology failed to demonstrate any significant difference in overall survival between patients who received MLNR during their operation, and those who did not. The authors conclude that subsolid nodules less than 30 mm in diameter, and peripheral solid nodules less than 20 mm in diameter should be treated with sublobar resection without MLNR.

The identification of small lung nodules is challenging during mini-invasive thoracic surgery. Unable to palpate them directly, surgeons have developed several methods to preoperatively localize pulmonary nodules, including the computed tomography-guided positioning of coils or metallic landmarks (hook wire) or bronchoscopic marking. We present a series of patients scheduled for the video-assisted thoracoscopic sublobar resection of small pulmonary nodules, in which we performed preoperative percutaneous computed tomography (CT)-guided nodule localization through the injection of a mixture of indocyanine green and human albumin. A total of 40 patients underwent a preoperative CT-guided injection of indocyanine green followed by VATS resection within 24 h. Patients tolerated the procedure well, no pain medication was administrated, and no complications were observed during the marking procedure. All pulmonary nodules were easily detected and successfully resected. the near-infrared dye marking solution of indocyanine green (ICG) with diluted human albumin was safe, effective, and easy to perform. The ICG solution has the potential to facilitate the accurate localization and resection of pulmonary nodules during VATS surgery, avoiding the risk of marker displacement/migration.