Assessing the efficacy and impact of minimally invasive thoracic surgery for diagnosing non-malignant pulmonary nodules

Introduction

The approach to the diagnosis of lung nodules is at a pivotal juncture, driven by advances in imaging technologies and evolving clinical guidelines. The detection of lung nodules, often incidental findings on computed tomography (CT) scans, presents a diagnostic challenge that straddles the realms of benign and malignant etiologies (1,2). Lung cancer, a leading cause of cancer-related mortality worldwide, underscores the importance of a timely and accurate diagnosis (3). However, the discovery of non-malignant nodules, while potentially less ominous, poses its own set of questions regarding the appropriate diagnostic and management strategies.

The traditional approach to lung nodule evaluation has largely centered on distinguishing malignant from benign processes, with biopsies reserved for those with a high suspicion of malignancy (4-6). This paradigm, however, is shifting towards a more nuanced understanding that recognizes the clinical significance of identifying the etiology of benign lung nodules (7). Non-malignant nodules can arise from a variety of conditions, including infectious, inflammatory, and benign neoplastic processes, each carrying distinct therapeutic and prognostic implications.

Minimally invasive thoracic surgery, particularly wedge resection, has emerged as a critical tool in determining the pathology associated with lung nodules (8). Beyond its established role in the management of malignant nodules, wedge resection offers a unique advantage in evaluating benign lesions. This surgical technique allows for comprehensive tissue sampling, enabling precise histopathological diagnosis that can significantly influence patient management (9). The procedure’s ability to yield definitive diagnoses is particularly valuable in cases where non-invasive methods, such as fine-needle aspiration or core needle biopsy, fail to provide conclusive results (10). The decision to proceed with surgical biopsy, however, is not without its considerations. The risks and benefits of the procedure must be carefully weighed, taking into account factors such as the nodule’s radiologic characteristics, the patient’s overall health status, and the potential impact on clinical management (11). The increasing interest in the application of wedge resection for non-malignant nodules underscores the need for robust evidence to guide clinical decision-making. This involves not only assessing the safety and efficacy of the procedure but also understanding its impact on patient care. Recent literature has begun to fill the gaps in our knowledge, offering insights into the utility of surgical biopsies in the context of benign lung nodules (6,7). These studies highlight the procedure’s diagnostic accuracy, safety profile, and its implications for altering treatment strategies. Yet, despite these advances, the literature remains fragmented, with ongoing debates about the optimal approach to lung nodule evaluation.

The present work aims to contribute to this evolving evidence by examining the efficacy and impact of minimally invasive thoracic surgery for diagnosing non-malignant pulmonary nodules. Through a comprehensive review of current practices, emerging evidence, and clinical outcomes, we seek to clarify the role of surgical biopsy in the management of benign lung nodules. By delineating the conditions under which surgical intervention is warranted and elucidating its implications for patient care, this study endeavors to provide a foundation for evidence-based guidelines that optimize the diagnostic pathway for lung nodules. In doing so, it not only addresses a critical gap in the literature but also advances our collective goal of improving patient outcomes through tailored, informed clinical decision-making. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1195/rc).

Methods

Study design

We conducted retrospective analysis of patient records from a prospectively maintained database to investigate the safety and efficacy of minimally invasive surgical biopsy for pulmonary nodules. This study, conducted at a single center, focused on evaluating the diagnostic and therapeutic outcomes of patients who underwent surgical biopsy for benign pulmonary nodules [Lung Reporting and Data System (L-RADS), 3]. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Northwestern Memorial Hospital (IORG0000247). Informed consent was not required for the purposes of this study given its retrospective and deidentified nature posing minimal risk to the subjects.

Patient selection

Our study included a cohort of 164 patients, aged 18–90 years, who underwent wedge resection between January 2017 and December 2021. Eligible patients were those with inconclusive pulmonary nodules or nodules that could not be adequately evaluated through non-surgical means such as fine-needle aspiration, core needle biopsy, or bronchoscopy based on radiological evaluation using either positron emission tomography (PET) or CT scan for assessment. Patients who had previously received inconclusive results from non-surgical attempts or for whom such attempts were not viable due to anatomical constraints also qualified. Exclusions were made for patients who had the procedure as inpatients for unrelated conditions, those diagnosed with malignant pathology, or those who required transition to more invasive surgeries like lobectomy or segmentectomy.

Data extraction

We extracted clinical data from Epic, Northwestern’s electronic medical record system, including demographics, medical history, radiologic, and pathology findings. A team trained in medical chart review handled data extraction, which was then anonymized and compiled in RedCap for analysis.

During a minimally invasive wedge resection, the patient was placed under general anesthesia. For video thoracoscopy, the surgeon made one or two 5 mm incision for instruments and camera and a 11 mm incision for a stapler. For robotic thoracoscopy, two 8 mm and one 12 mm incisions were made for the robotic ports. The thoracoscopic or robotic approach provides a magnified view of the surgical site, aiding the surgeon in precise visualization and manipulation of the lung tissue. Operative time for a minimally invasive wedge resection varied depending on factors such as the complexity of the lesion, however, in general, these procedures are known for shorter operative times compared to traditional open surgeries. Complications associated with the surgical biopsies were independently reviewed by adjudicators outside the surgical team. These complications, categorized according to standard criteria, ranged from pneumonia and pulmonary embolism (PE) to postoperative bleeding and infection, among others. The occurrence of one or more complications was recorded for each affected patient.

Statistical analysis

The study analyzed the impact of surgical biopsies on patient management by comparing treatment protocols before and after biopsy. We documented any changes in treatment approaches, including adjustments in therapy, reduction in imaging frequency, cessation of follow-up, initiation of consultations with other specialties, or the need for additional surgeries. Descriptive statistics were then employed to summarize the patient demographics, complication rates, and adjustments in treatment protocols, focusing on frequencies and proportions for categorical variables.

Results

Study cohort

The study cohort comprised a total of 154 participants with a mean age of 61.4 [± standard deviation (SD), 14.0] years and a mean body mass index (BMI) of 28.1 (± SD, 5.6) kg/m² (Table 1). The distribution of gender revealed 67 males (44%) and 87 females (56%). Smoking history varied, with 6 participants (4%) identified as current smokers, 78 (51%) as former smokers, and 76 (49%) as never smokers. In terms of ethnicity, 11 participants (7%) identified as Hispanic or Latino, 141 (92%) as not Hispanic or Latino, and 2 (1%) were classified as unknown/not reported. Regarding race, the cohort included individuals from diverse backgrounds: American Indian/Alaska Native (1%), Asian (3%), Black or African American (10%), White (84%), and individuals identifying with more than one race (2%). A subset of participants reported a history of diabetes (19%) and cardiovascular disease or hypertension (75%). Only 3% had a history of lung cancer, while 38% reported a history of other cancers, with breast, prostate, and colon and rectum being the most prevalent types. Chronic lung conditions were reported by 50% of participants, with restrictive and obstructive conditions affecting 28% and 20%, respectively. A majority of participants had not experienced coronavirus disease 2019 (COVID-19) (90%) or previous lung infections (82%). Lung surgeries were reported by 8% of participants, including lung resections (3%), predominantly lobectomy. Chest procedures, excluding lung surgeries, were documented in 40% of cases.

Characterization

The mean size of the pulmonary nodule was 13.8 (± SD, 8.3) mm. Notably, 27 cases had unspecified sizes, thus we excluded the unverified data for the purpose of characterizing the nodules. These patients were included in our final analysis given we did not correlate size to patient outcomes or changes in treatment. The nodules exhibited varied presentations, 34.1% of patients presented with a solitary nodule, while 65.9% of patients presented with multiple nodules. In terms of laterality, 3.2% of patients demonstrated bilateral nodule of indeterminate significance, while 3.9% demonstrated a unilateral pulmonary nodule. Radiology reports for 92.7% of patients used descriptors such as “scattered” or “diffuse” small nodules in the context of a primary nodule of interest without specifying laterality of these small and clinically irrelevant distributions. Regarding calcification, 79% were not calcified, 11% exhibited calcification, and 11% lacked definitive details. For those with nodules characterized, a majority were predominantly solid in nature (80.5%) were solid, with an additional 10.6% partially solid, while 5.7% were not solid, and 3.3% were cavitated. Additionally, 19.5% of patients had nodules associated with hilar or mediastinal lymphadenopathy. Standardized uptake values (SUVs) were not available in 56% of cases where a PET scan was not obtained prior to biopsy. However, of those with corresponding data, SUV was abnormal in 58.5% (greater than or equal to 2.5), normal in 41.5%. The SUV values ranged from 0 to 12.8, with an average of 3.78. The first quartile was 1.5, the second quartile (median) was 3, the third quartile was 5.8, and the fourth quartile was 12.8. These findings underscore the heterogeneity in pulmonary nodule characteristics within the study population, emphasizing the importance of detailed radiological assessments for accurate clinical interpretation.

Pathology

Within our cohort with low suspicion for malignancy based on clinical and radiographic assessment, 91.9% demonstrated benign pathology, 3.4% were malignant, and 4.7% were inconclusive after the first procedure. Pathological examination of the lung biopsy specimens yielded the following findings: 32.43% pulmonary fibrosis, 22.97% to be non-caseating granulomas, 19.59% caseating granulomas, 4% active infection, 2.03% vasculitis, and 2% to be benign neoplasm. These diverse pathological findings underscore the complexity and heterogeneity of the nodules that prompted surgical biopsy in this patient cohort (Figure 1).

Figure 1 Complication type experienced by patient in 30-day post-operative period. “Other” includes atypical complications including pain requiring hospitalization, reactions to medication during or after surgery, or exacerbation of comorbid condition. No atrial fibrillation, DVTs, re-intubation, or UTIs occurred. DVT, deep vein thrombosis; PE, pulmonary embolism; UTI, urinary tract infection.

Impact on clinical care following lung biopsy

The lung biopsy results led to altered treatment protocols in all patients. Pathology of the indeterminate pulmonary nodules obtained through minimally invasive surgical biopsy resulted in discontinued follow-up for 36.9% of patients with complete cessation of care outside of routine surgical follow-up. Of patients with pre-procedure scheduled imaging regimens, 43.0% of patients were able to either discontinue or decrease their imaging interval. Imaging surveillance burden in terms of interval or total time was extended for 5.4% of patients with infectious findings. New consults to a service outside of thoracic surgery were initiated in 26.2% of patients, with the largest consult being infectious disease. Modifications to pharmacotherapy regimens were driven by biopsy in 26.9% of patients. Further surgical procedure and referral to clinical trial were the least likely outcomes of biopsy accounting for two cases within the cohort (Figure 1).

Safety of minimally invasive lung biopsy

Complications following minimally invasive surgical biopsy of pulmonary nodules were evaluated using the Clavien-Dindo classification system. Among the 154 patients included in our study, the majority, comprising 92.6% (138 individuals), experienced no complications (Figure 2). Minor complications (Clavien-Dindo grade I) included pneumonia in 2 patients (1.34%), PE in 2 patients (1.34%), and other complications including need for adjusted analgesia, corrected electrolytes, or refined disposition plans due to co-morbid conditions (6.0%). A single case of bleeding was reported, classified as a grade II complication, requiring pharmacologic intervention without further invasive treatment. Notably, complications such as atrial fibrillation, deep vein thrombosis (DVT), intubation, and urinary tract infection (UTI) did not occur in any of the patients in this study. Further, no patients experienced severe complications requiring major surgical intervention (grade III), life-threatening complications (grade IV), or complications resulting in death (grade V).

Figure 2 Change in protocol based on results of minimally invasive biopsy.

In addition to complications, we observed length of stay after the minimally invasive surgical biopsy. Ten patients were hospitalized for comorbid conditions unrelated to the pulmonary nodule prior to and after the procedure and were excluded from this analysis. For the remaining 144 patients, the length of hospital stay ranged from 1 to 4 days, with an average stay of 1.3 days and a median of 1 day from the time of the procedure. In terms of safety, 90% of patients were discharged ambulatorily within 24 hours. No re-admissions or mortalities were recorded at 30 days.

Discussion

The study aimed to assess the safety and diagnostic value of minimally invasive surgical biopsies for pulmonary nodules, yielding significant insights for patient management. It established the safety of wedge resection as a diagnostic tool for lung nodules with low suspicion for malignancy, as evidenced by an absence of re-admissions or mortalities within 30 days post-biopsy. This highlights the procedure’s low risk to patients across a diverse cohort.

The diagnostic value was illuminated through the identification of various pathologies, such as infectious or autoimmune granulomas and pulmonary fibrosis, underlining the importance of providing a comprehensive diagnostic picture even for non-malignant nodules. This breadth of findings reinforces the utility of biopsy in identifying specific etiologies of pulmonary nodules, which may otherwise remain undiagnosed or be misclassified without tissue confirmation. Importantly, biopsy results led to notable adjustments in collaborative clinical care of patients in 26.1% of cases, and altered management, with 36.9% of patients having follow-up care discontinued and 26.9% experiencing medication adjustments. The ability to secure a definitive diagnosis guided individualized treatment strategies and promoting informed decision-making in patient care. Our inclusive study design, which did not restrict participants to any specific geographic region and encompassed patients from both in-state and out-of-state locations, suggests that these findings have broad applicability and reflect a diverse patient demographic. This shift toward targeted therapeutic interventions not only optimizes patient outcomes by addressing the underlying pathology but also enhances healthcare resource utilization by reducing unnecessary follow-ups and limiting extensive diagnostic workups for indeterminate nodules. Thus, our study demonstrates the use of minimally invasive surgical biopsy of indeterminate nodules for diagnostic assessment has the potential for profound impact on patient management following biopsy results. Safety of the procedure as demonstrated by minimal complications with no mortality within 30 days or re-admission supports the safety of this tool.

Accurate risk stratification, prior work-up, and patient preference is critical to minimize unnecessary risk, cost, and patient anxiety associated with pulmonary nodules (11,12). This must be taken into account when determining when to proceed with minimally invasive surgical biopsy compare to an imaging approach. Surgical biopsy provides definitive diagnosis that may provide clinicians with critical information for the treatment course. A key observation was the minimally invasive nature of the procedure, with a notable percentage of patients being discharged within 24 hours, supporting the healthcare trend towards reducing hospital stays and encouraging outpatient procedures. This approach not only aids in cutting healthcare costs but also improves patient satisfaction, reduce unnecessary follow-up, reduces anxiety, and may improve adherence when follow-up is required (11,13).

All modalities of assessing pulmonary nodules have their inherent risks and benefits. Traditionally, lung nodules can be biopsied using image-guided and bronchoscopic methods including transbronchial biopsy, electromagnetic navigation bronchoscopy, virtual bronchoscopy (VB), radial endobronchial ultrasound, ultrathin bronchoscope, and guide sheath with an aggregate diagnostic yield of 70% (14). Given the advancement of recent advanced navigational technologies that better map and allow access to the periphery of the lung, diagnostic yield of peripheral pulmonary nodules has improved (15). Nevertheless, our data suggests that histological analysis of non-malignant nodules provides significant clinical information that could impact patient care and can be considered as a safe alternative when other modalities have been unsuccessful. Surgical biopsy, particularly wedge resection, often provides a larger tissue sample than CT-guided or bronchoscopic biopsies, potentially leading to a more definitive diagnosis, especially in complex cases where non-malignant diseases are suspected (16). While at our center, we found that surgical biopsies are extremely safe, they may have attendant risks and a potentially longer recovery time compared to the less invasive CT-guided or bronchoscopic biopsies based on the expertise. However, the latter techniques may have a higher rate of non-diagnostic samples, requiring additional procedures (14). Therefore, choice between these methods would depends on various factors, including the nodule’s location, patient’s overall health, the potential need for immediate therapeutic intervention, and the expertise available. CT-guided and bronchoscopic biopsies should be preferred as the first-line modality for nodules easily accessible and in patients at higher surgical risk. However, when feasible and suitable, surgical biopsy can significantly alter patient management, providing a clear direction for treatment in cases of benign conditions that mimic malignancy on imaging studies. This direct therapeutic impact contrasts with the more limited tissue samples obtained through CT-guided or bronchoscopic methods, which might not always allow for a comprehensive evaluation of the nodule. Nevertheless, the decision to employ one method over another should be guided by a multidisciplinary team, considering the balance between diagnostic yield, patient safety, and the overall impact on patient care. Towards that, “lung nodule” clinics or programs have been implemented including at Northwestern Medicine.

Our study, despite providing valuable insights into the role of surgical biopsy in pulmonary nodule evaluation, is subject to several limitations. Firstly, its retrospective design inherently limits our ability to control for confounding variables and biases associated with patient selection and data collection, particularly in tracking long-term changes to imaging if completed or followed up at outside institutions. The single-center setting may also limit the generalizability of our findings to broader populations, as institutional practices and patient demographics can vary significantly. Additionally, the absence of a comparison group undergoing alternative diagnostic modalities, such as CT-guided or bronchoscopic biopsies, restricts our capacity to directly compare the efficacy and safety of different biopsy methods. Another limitation is the reliance on medical records for data extraction, which may be affected by incomplete or inconsistent documentation. Future studies could address these limitations by incorporating prospective, multicenter designs, comparison groups, and standardized data collection methods to enhance the robustness and applicability of the findings.

Nevertheless, the study underscores the crucial role of minimally invasive surgical biopsy in the multidisciplinary management of pulmonary nodules, advocating for its continued use due to its significant contributions to patient care. Future collaborative research efforts are essential to deepen our understanding and reinforce the clinical utility of this diagnostic approach.

Conclusions

The gathered data unequivocally supports the assertion that minimally invasive surgical biopsy is a highly effective method of offering precise diagnostic outcomes for non-malignant nodules. The analysis reveals a marked improvement in patient outcomes, by allowing the opportunity for additional consults, tailored pharmaceutical treatment, and decreased need for long-term follow-up, thereby showcasing the positive impact of employing wedge resection as a diagnostic tool. The study emphasizes the significance of this procedure in refining our diagnostic approach and suggests use as an adjunct to our current guidelines regarding pulmonary nodules. As we navigate the evolving landscape of thoracic surgery, this conclusive data underscores the enduring value of wedge resection as a pivotal element in diagnosing non-malignant pulmonary nodules, thereby contributing to advancements in patient care and diagnostic accuracy.

Acknowledgments

The authors are grateful to acknowledge the help of Michal Shalman B. S. in her assistance with preparing the table for presentation, and Elena Susan B. A. in her coordination of the writing process. We further appreciate having had the opportunity to present this research in conjunction with 19^th Academic Surgical Congress.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1195/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1195/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1195/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1195/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Northwestern Memorial Hospital (IORG0000247). Informed consent was not required for the purposes of this study given its retrospective and deidentified nature posing minimal risk to the subjects.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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