Impact of surgical margins on treatment outcomes in pulmonary resections for Aspergillus-related fungal infections: an initial analysis
José de Sá Moraes Neto1
, Jaqueline Schaparini Fonini2
, Ellen Caroline Toledo do Nascimento2
, Paulo Manuel Pêgo-Fernandes2
, Alessandro Wasum Mariani2
Contributions: (I) Conception and design: JdS Moraes Neto; (II) Administrative support: AW Mariani; (III) Provision of study materials or patients: JdS Moraes Neto; (IV) Collection and assembly of data: JdS Moraes Neto; (V) Data analysis and interpretation: JdS Moraes Neto; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Background: Pulmonary resection is an important adjunct to antifungal therapy in selected patients with Aspergillus-related lung disease. However, the impact of surgical margin status on treatment outcomes remains poorly defined. The objective is to compare the impact of surgical margins on treatment response in patients with pulmonary fungal infections, analyzing persistence of symptoms, perpetuation of fungal colonization, and disease recurrence.
Methods: This retrospective study analyzed patients treated between 2020 and 2024 with inflammatory/infectious pulmonary diseases caused by Aspergillus, undergoing pulmonary resection due to complications or as an adjunct to clinical treatment with curative intent. Patients were divided into two groups: tangential margin (distance to pulmonary margin <0.1 cm) and non-tangential margin (distance >0.1 cm). Patients were followed for one year. Exclusion criteria included incomplete records, loss to follow-up, or pneumonectomy cases.
Results: Nineteen patients were included, of whom four experienced disease recurrence. All recurrence cases occurred in the “tangential margin” group. Tangential margins were strongly associated with symptom persistence, with an odds ratio (OR) of 11.0 [95% confidence interval (CI): 1.30–140.9, P=0.04]. Patients in this group also showed a smaller reduction in Aspergillus serology titers (50%) compared to the “non-tangential margin” group (75%), with statistical significance (P=0.04). The study also examined the correlation between the extent of lung disease and treatment outcomes but found no statistically significant association with recurrence, symptom persistence, or serology titer reductions.
Conclusions: As lung-sparing surgeries become more prevalent, an adequate surgical margin remains critical to achieving disease-free survival. This study suggests the importance of ensuring sufficient margins in pulmonary resections for fungal infections to optimize therapeutic outcomes. Additional research is needed to confirm our findings.
Keywords: Pulmonary resection; fungal infection; Aspergillus; surgical margin; disease recurrence
Submitted Feb 11, 2026. Accepted for publication Apr 09, 2026. Published online May 27, 2026.
doi: 10.21037/jtd-2026-1-0386
Highlight box
• In this retrospective study of patients undergoing pulmonary resection for Aspergillus-related disease, tangential surgical margins (<0.1 cm) were associated with worse outcomes, including symptom persistence, disease recurrence, and a smaller reduction in Aspergillus serology titers. Notably, all recurrences occurred in the tangential-margin group.
What is known and what is new?
• Pulmonary aspergillosis, particularly chronic pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis, may require surgical resection in selected patients with hemoptysis, localized disease, or failure of antifungal therapy. Although surgical margin adequacy is a well-established prognostic factor in oncologic lung resections, its role in fungal lung infections remains poorly understood.
• Our study provides novel evidence that surgical margin distance is also relevant in infectious pulmonary disease. Margins <0.1 cm were associated with symptom persistence (odds ratio 11.0), reduced serological response, and all observed recurrences, suggesting that inadequate margins may allow persistence of fungal disease after resection.
What is the implication, and what should change now?
• Achieving adequate surgical margins should be considered an important objective during pulmonary resection for Aspergillus-related infections, even when lung-sparing approaches are pursued. Surgeons must balance parenchymal preservation with complete disease clearance. These findings support further prospective, multicenter studies to establish standardized surgical recommendations and determine optimal margin thresholds for fungal lung disease.
Introduction
Pulmonary aspergillosis encompasses a spectrum of clinical syndromes caused by Aspergillus spp., with chronic cavitary pulmonary aspergillosis (CCPA) and aspergilloma representing the most common forms requiring surgical intervention (1-3). These conditions frequently occur in patients with underlying structural lung disease, such as previous tuberculosis, chronic obstructive pulmonary disease, or sarcoidosis, leading to persistent cavities that serve as a nidus for fungal colonization (4-7). Although antifungal therapy remains the cornerstone of management, it is often insufficient in cases of localized disease complicated by hemoptysis, persistent symptoms, or treatment failure, where surgery may play a curative or adjunctive role (8-11).
Chronic pulmonary aspergillosis (CPA) is a disease characterized by the destruction of pulmonary architecture, primarily affecting patients with pre-existing lung conditions (2,6). It has a global prevalence of approximately 42 cases per 100,000 inhabitants, with a higher incidence in underdeveloped and developing regions. It is estimated that there are only about 3 million cases of CPA worldwide, of which 1.2 million are associated with complications of pulmonary tuberculosis (12).
Surgical resection in these patients is technically challenging due to extensive pleural adhesions, distorted anatomy, and risk of perioperative complications (3,10). While anatomical lobectomy remains the standard approach, lung-sparing techniques such as segmentectomy or wedge resection have gained traction, particularly in patients with limited pulmonary reserve. However, the implications of surgical margins in fungal disease remain poorly defined, unlike in oncologic resections, where margin adequacy directly correlates with recurrence and survival (9).
Given the invasive yet indolent nature of CPA, insufficient resection margins may allow for persistence of fungal elements, leading to disease recurrence or incomplete symptom resolution. Despite this concern, there is limited evidence evaluating the prognostic impact of surgical margin size in pulmonary resections for fungal infections.
This study aims to evaluate the impact of surgical margin distance on treatment outcomes, including symptom persistence, recurrence, and serological response, in patients undergoing pulmonary resection for Aspergillus-related infections. Clarifying this relationship is crucial for informing surgical planning and optimizing patient outcomes in this complex population. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0386/rc).
Methods
Study population
We retrospectively collected data from outpatient patients presenting with inflammatory/infectious pulmonary diseases caused by Aspergillus who underwent surgical treatment between January 2020 and January 2024. The Ethics Committee of the Hospital das Clínicas, University of São Paulo School of Medicine approved this study with number (No. CAAE 33365720.2.0000.0068). The requirement for informed consent was waived due to the retrospective nature of the study.
Diagnostic definition
All patients underwent chest computed tomography (CT) using multidetector scanners. Patients maintained follow-up with the Thoracic Surgery and Pneumonology team. All patients were discussed in a multidisciplinary discussion for surgery indication. Aspergillus infection was defined based on specific radiological criteria, including aspergilloma or CCPA, and serum test (Aspergillus serology titers).
For the purpose of standardizing the measurement of the surgical margin, values below 0.1 cm were defined in conjunction with the pathology department of the service as a tangential margin, since the measurement for values below this has a higher probability of measurement error. Values above this cutoff point are expressly shown in the pathology reports.
Inclusion and exclusion criteria
We included all patients with radiologically and serologically confirmed Aspergillus infection, and patients for whom surgery was indicated were discussed in the multidisciplinary discussion. Patients were excluded if medical records were incomplete, did not attend outpatient follow-up during the 12-month observation period, or patients submitted to pneumonectomy.
All patients received postoperative antifungal therapy, typically with oral azole agents, for a duration determined by multidisciplinary evaluation based on disease severity and response.
The evaluation of disease recurrence and/or relapse was assessed by laboratory criteria (Aspergillus serology). The symptoms analyzed were the same as the indicators for lung resection: hemoptysis and suppuration. The follow-up occurred in two phases—an earlier one, at 90 days post-surgery, and a later one, between 270 and 360 days. Figure 1 demonstrates the sample.
Statistical analysis
Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Chicago, IL, USA) for data management and descriptive statistics, and the R statistical environment (R Foundation for Statistical Computing, Vienna, Austria) for inferential analyses, including hypothesis testing and logistic regression modeling. This combined approach was adopted to ensure analytical flexibility and reproducibility. Data were presented using descriptive statistics, including mean, standard deviation, median, and interquartile range for quantitative variables, and absolute numbers with corresponding percentages for categorical variables. The significance of differences between groups was assessed using the Mann-Whitney U test for quantitative variables. Differences between categorical variables were evaluated using Fisher’s exact test. All analyses were conducted using the R programming environment, with a statistical significance threshold set at P<0.05.
With the sample size, a robust multivariable analysis is not allowed, being a limitation of the present study and the possibility of residual confounding should be understood.
Results
General population characteristics
Following a comprehensive review of all medical records, using predefined inclusion and exclusion criteria, a total of 19 patients were included in this study for data analysis.
In the initial analysis, participants were categorized into two groups based on the distance of the pulmonary margin. Patients who exhibited a distance to the pulmonary margin of less than 0.1 cm were assigned to the “tangential margin” group (n=6). Those presenting distance to pulmonary margin greater than or equal to 0.1 cm were classified under the “non-tangential margin” group (n=13).
General characteristics
The overall mean age of participants was 47 years (range, 43–62 years). Considering the general study population, males were more prevalent (12 participants, 63.0%). About ethnicity, white was most prevalent (68.0%), followed by brown (21.0%).
About the status before the surgery, participants were classified on a scale. First, about the American Society of Anesthesiology, 63.0% the participants had mild to moderate systemic disease. The nutritional status of the patients was determined for body mass index (BMI)—in the present study, the mean was 24.9 kg/m2 (interquartile interval between 22.0 and 27.7 kg/m2).
Aspergilloma was more prevalent Aspergillus presentation—10 patients, while nine participants were chronic cavitary pulmonary aspergillosis.
Lobectomy is the most frequently performed procedure in the sample, 14 patients (74.0%). Four participants (21.0%) had submitted for anatomical segmentectomy, and one patient (5.0%) performed wedge resection.
In patients with tangential margin, four patients had CCPA and two participants had aspergilloma. Lobectomy was performed in three patients, while two patients had submitted for anatomical segmentectomy and one patient performed wedge resection.
About non-tangential margin, six patients had CCPA and seven participants had aspergilloma. Lobectomy performed in 11 patients and two patients had submitted for anatomical segmentectomy.
Upper lobes were the most affected—14 patients (74.0%) in the right upper lobe, 4 patients (21.0%) in the left upper lobe, and 1 (5.0%) in the middle lobe.
The indications for surgery were as follows: 6 participants (31.5%) had recurrent infection, 3 patients (15.8%) experienced hemoptysis, and 10 patients (52.7%) underwent surgery as an adjuvant clinical treatment.
Table 1 presents the general characteristics of the sample.
Table 1
| Variables | Value |
|---|---|
| Age, years | 47.0 (43.0, 62.0) |
| Sex | |
| Female | 7 (37.0) |
| Male | 12 (63.0) |
| BMI, kg/m2 | 24.9 (22.0, 27.7) |
| Surgery indication | |
| Hemoptysis | 3 (15.8) |
| Recurrent infection | 6 (31.5) |
| Adjuvant clinical treatment | 10 (52.7) |
| Pulmonary resection | |
| Lobectomy | 14 (74.0) |
| Wedge | 1 (5.0) |
| Segmentectomy | 4 (21.0) |
| Affected pulmonary area | |
| RUL | 14 (74.0) |
| ML | 1 (5.0) |
| LUL | 4 (21.0) |
| Aspergillus presentation | |
| Fungal ball | 10 (53.0) |
| Chronic cavitary pulmonary | 9 (47.0) |
Data are presented as n (%) or median (Q1, Q3). Pearson’s Chi-squared test; Fisher’s exact test; Wilcoxon rank sum exact test. BMI, body mass index; LUL, left upper lobe; ML, middle lobe; RUL, right upper lobe.
Perioperative outcomes
Four patients had disease recurrence during follow-up for one year. All participants were in the “tangential margin” group.
Association between parenchyma margin and persistence of symptoms, recurrence of disease, and Aspergillus serology titers were done.
About the persistence of symptoms, tangential margins are strongly associated with symptom perpetuation, with an odds ratio (OR) of 11.0 and 95% confidence interval (CI) of 1.30 to 140.9 (P=0.04), as visualized in Table 2.
Table 2
| Group | OR | 95% CI | P value |
|---|---|---|---|
| Non-tangential (ref.) | 1.00 | – | – |
| Tangential | 11.0 | 1.30–140.9 | 0.04 |
Binary logistic regression. CI, confidence interval; OR, odds ratio.
Eleven participants had positive Aspergillus serology titers before the surgery, six patients in the “non-tangential margin” group and five patients in the “tangential margin” group. In the “tangential margin” group, the reduction in Aspergillus serology titers was 50% and in the “non-tangential margin” group, the reduction was 75%, with statistical significance (P=0.04), as we visualize in Table 3.
Table 3
| Variable | Total | Non-tangential group | Tangential group | P value |
|---|---|---|---|---|
| Ratio, % | 75.0 (50.0, 75.0) | 75.0 (74.0, 94.0) | 50.0 (50.0, 50.0) | 0.04 |
Data are presented as mean (IQR). Mann-Whitney test. IQR, interquartile range.
The relationship between the size of the lung area affected by the fungal disease and disease recurrence, persistence of symptoms, and reduction in serology titer was also analyzed. However, there was no relationship with statistical significance, as demonstrated in Tables 4,5.
Table 4
| Variable | OR | 95% CI | P value |
|---|---|---|---|
| Lesion size | 0.96 | 0.74–1.19 | 0.75 |
†, Binary logistic regression. CI, confidence interval; OR, odds ratio.
Table 5
| Variable | OR | 95% CI | P value |
|---|---|---|---|
| Lesion size | 0.91 | 0.73–1.09 | 0.35 |
†, Binary logistic regression. CI, confidence interval; OR, odds ratio.
All patients who developed recurrence had undergone parenchymal-sparing resections (segmentectomy or wedge resection), and all belonged to the “tangential margin” group.
Discussion
This study addresses a critical and understudied aspect of pulmonary surgery in the management of Aspergillus-related infections: the impact of surgical margin size on treatment outcomes. Our findings suggest a strong association between narrow surgical margins (less than 0.1 cm, defined here as “tangential”) and poorer clinical outcomes, particularly in terms of symptom persistence, recurrence, and reduced serological response.
The statistically significant association between tangential margins and symptom persistence (OR 11.0; 95% CI 1.30–140.9; P=0.04) reinforces previous evidence that incomplete or marginal resections are insufficient to fully eradicate fungal burden in the lung parenchyma, especially in cases of CCPA or complex aspergillomas (1,10,12). These entities are known for their tendency to invade surrounding structures and persist in residual cavitary spaces even after anatomical resections (4).
Furthermore, the observed difference in Aspergillus serology titers—a 75% reduction in the non-tangential group versus only 50% in the tangential group (P=0.04)—suggests that adequate margins may play a role in immunological clearance of fungal elements. Although serological markers have limitations in sensitivity and specificity, they remain useful adjuncts in monitoring CPA treatment response (8).
Interestingly, lesion size did not correlate with recurrence or symptom persistence, contrary to what might be expected in oncologic models of resection. This highlights the unique biological behavior of fungal infections, where localized but persistent foci can remain active despite relatively small lesion volumes (6,13).
Considering the growing use of parenchymal-sparing strategies such as segmentectomies and wedge resections, particularly in patients with limited pulmonary reserve, these findings raise concern. Although these techniques aim to preserve lung function, our data suggest they may compromise infectious control if margins are inadequate. This underscores the importance of a multidisciplinary surgical strategy that balances functional preservation with complete eradication of disease (10).
Our study is limited by its retrospective design and small sample size, which restricts statistical power. Nonetheless, the significant differences observed between groups, despite these limitations, underscore the potential clinical importance of surgical margin assessment in fungal resections. Future prospective studies, ideally multicentric and involving volumetric and histopathological correlation, are necessary to refine surgical guidelines for this patient population.
Since these are initial data, with a restricted sample of participants, the present study aims to bring to light that the surgical margin in resections for infectious disease should be better explored in future prospective studies.
Conclusions
In pulmonary resections for Aspergillus-related infections, particularly CCPA and aspergillomas, achieving adequate surgical margins (>0.1 cm) is associated with better clinical outcomes, including lower rates of symptom persistence and recurrence, as well as greater reductions in Aspergillus serology titers. These findings support a more assertive surgical approach in resection planning, especially in patients with a curative intent. As lung-sparing surgeries become more common, ensuring adequate margins in fungal resections may be vital to improve long-term disease control. Further studies are warranted to develop evidence-based surgical standards for fungal infections of the lung.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0386/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0386/dss
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0386/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-2026-1-0386/coif). A.W.M. reports consulting fees from Astra-Zeneca and Merck Sharp and Dohme; honoraria for lectures and educational events from Intuitive, Astra-Zeneca, and Merck Sharp and Dohme; and served on advisory boards for Astra-Zeneca and Merck Sharp and Dohme. The other 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 Ethics Committee of Hospital das Clínicas, University of São Paulo School of Medicine (No. CAAE 33365720.2.0000.0068). The requirement for informed consent was waived due to the retrospective nature of the study.
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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