Exploratory analysis of spread through air spaces and staple-line recurrence after wedge resection for colorectal lung metastases

Introduction

Colorectal cancer frequently metastasizes to the lung, and pulmonary metastasectomy can provide long-term survival in appropriately selected patients (1-3). Wedge resection is widely used for pulmonary metastases from colorectal cancer because it preserves lung parenchyma and pulmonary function (4-6). However, local recurrence near the resection site, particularly around the staple line, remains an important local control issue, highlighting the need for appropriate evaluation of surgical margins (7-10).

Previous studies have emphasized margin-related determinants of local recurrence after wedge resection for pulmonary metastases, including tumor/margin ratio and the relationship between tumor size and surgical margin length (9,11). Collectively, these studies indicate that the adequacy of local resection is a key determinant of local control.

Spread through air spaces (STAS), defined as tumor cell clusters spreading within alveolar spaces beyond the edge of the main tumor, has been recognized as a pathological feature associated with recurrence and poor prognosis in primary lung cancer, particularly after limited resection (12-14). However, colorectal lung metastasis differs from primary lung cancer both clinically and biologically, and the clinical meaning of STAS in colorectal lung metastases remains less well established. In pulmonary metastases from colorectal cancer, Takeda-Miyata et al. reported that STAS was associated with poor prognosis and that the farthest STAS distance was an independent risk factor for surgical margin relapse (15). These findings suggest that STAS may have clinical relevance in colorectal lung metastases, but its role in staple-line recurrence after wedge resection remains unclear.

Specifically, it is uncertain whether staple-line recurrence after wedge resection should be understood primarily as a technical problem related to margin adequacy, or whether tumor biological features such as STAS also modify local recurrence risk. Therefore, the aim of this study was to investigate the association between STAS and staple-line recurrence in patients who underwent wedge resection as the initial surgical procedure for pulmonary metastases from colorectal cancer. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1247/rc).

Methods

Study design and patients

This was a single-center retrospective observational study of patients who underwent wedge resection as the initial pulmonary operation for colorectal lung metastases at the Department of Thoracic and Cardiovascular Surgery, Osaka Medical and Pharmaceutical University. 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 Osaka Medical and Pharmaceutical University (No. 2024-068). The requirement for individual written informed consent was waived owing to the retrospective observational design of the study. Information regarding the study was disclosed using an opt-out approach, and patients were given the opportunity to decline participation.

Patients who underwent surgery for pulmonary metastases from colorectal cancer at Osaka Medical and Pharmaceutical University Hospital between January 2011 and December 2020 were identified from a prospectively maintained surgical database and electronic medical records. Eligible lesions were pulmonary metastases from histologically confirmed colorectal cancer that were treated by wedge resection during the initial pulmonary operation and for which the pathological surgical margin could be measured on the resected specimen. We further confirmed that the wedge-resected pulmonary lesion had been pathologically diagnosed as metastatic colorectal adenocarcinoma and that hematoxylin and eosin-stained slides were available for evaluation of tumor size, pathological surgical margin, STAS status, and farthest STAS distance. Patients were also required to have undergone chest computed tomography (CT) follow-up for at least 12 months after surgery, unless recurrence or death had been confirmed within 12 months. Patients were excluded if they had pulmonary metastases from a non-colorectal primary tumor, concomitant primary lung cancer precluding definitive distinction from metastatic disease, palliative resection (R2 resection), or inadequate pathological material for the required histopathological assessment because of missing or poor-quality slides.

The lesion-level cohort consisted of pulmonary metastases from colorectal cancer that were treated by wedge resection during the initial pulmonary operation. Lesions treated by lobectomy or segmentectomy were not included in the analysis. In patients with multiple pulmonary metastases treated by different surgical procedures during the initial operation, only lesions treated by wedge resection were included in the present cohort. Patient-level variables, including the number of metastases and laterality of surgery, were recorded at the time of the initial pulmonary operation. Ultimately, 70 patients with 70 wedge-resected lesions were included in the analysis (Figure 1).

Figure 1 Flow diagram of lesion selection. The final cohort included 70 wedge-resected lesions from 70 patients. Lesions treated by lobectomy or segmentectomy were excluded from the analysis.

Surgery and postoperative follow-up

Wedge resection was performed via either thoracotomy or thoracoscopic approach using stapling devices to resect the lung parenchyma containing the tumor. The thoracic surgeons attempted to secure an adequate parenchymal margin whenever feasible. Intrathoracic lymph node dissection or sampling was not performed during the initial pulmonary metastasectomy. Intraoperative frozen-section assessment of the surgical margin was not routinely performed, and cytological margin assessment, including scraping cytology, lavage cytology, run-across cytology, or stapling-cartridge lavage cytology, was not performed. Postoperative follow-up consisted of chest CT every 6 months during the first 2 years and every 6 to 12 months thereafter, with additional systemic evaluation performed as clinically indicated.

Pathological evaluation

Resected specimens were formalin-fixed, paraffin-embedded, and processed for hematoxylin and eosin staining. Pathological tumor size was defined as the maximum diameter on the maximal cut surface. Pathological surgical margin was measured as the distance from the tumor edge to the nearest staple line on a specimen that had been reinflated with formalin immediately after resection. Tumor size and surgical margin were measured macroscopically by a pathologist and recorded in the final pathology report. When the distance between the tumor and the staple line was very close, the margin width was measured microscopically. Tumor/margin ratio was defined as pathological tumor size divided by pathological surgical margin.

Representative radiological and pathological findings are shown in Figure 2A-2D. STAS was assessed according to the criteria proposed by Kadota et al. as tumor cell clusters present within alveolar spaces beyond the edge of the main tumor (Figure 2B,2C) (12). After screening the tumor periphery at low magnification, detailed assessment was performed at high magnification, and the distance from the tumor edge to the farthest STAS was measured in STAS-positive lesions. Pathological evaluation was performed by three reviewers with experience in thoracic pathology (SF, KT, and HK) through consensus review using a multiheaded microscope. All three reviewers were blinded to postoperative staple-line recurrence status during pathological assessment. Because STAS status was determined by consensus review, interobserver agreement before consensus review was not calculated.

Figure 2 Representative radiological and pathological findings. (A) Preoperative chest computed tomography showing colorectal lung metastasis. (B,C) Hematoxylin and eosin-stained sections showing STAS beyond the main tumor edge. Arrows indicate STAS. Scale bars indicate 500 µm (B) and 200 µm (C). (D) Postoperative computed tomography showing staple-line recurrence. STAS, spread through air spaces.

Definition of staple-line recurrence and survival endpoints

Staple-line recurrence was defined as the appearance of a new or enlarging nodular lesion adjacent to the staple line of the resection site, generally within 2 cm, that was clinically judged to represent local recurrence of colorectal lung metastasis on postoperative imaging follow-up (Figure 2D) (9). Cases confirmed pathologically by repeat resection were regarded as definitive recurrences, and cases diagnosed based on serial imaging findings and interval change were also included in the analysis.

Overall survival (OS) was defined as the interval from the date of initial pulmonary wedge resection to death from any cause or last follow-up. Disease-free survival (DFS) was defined as the interval from the date of initial pulmonary wedge resection to recurrence at any site or death from any cause.

Statistical analysis

Continuous variables are presented as median (interquartile range) or mean ± standard deviation, and categorical variables as frequency (%). Comparisons of clinicopathological variables according to the presence or absence of staple-line recurrence were performed using the t-test or Wilcoxon rank-sum test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables.

To identify factors associated with staple-line recurrence, univariable logistic regression analyses were first performed to evaluate the associations of preoperative carcinoembryonic antigen level, STAS status, farthest STAS distance, tumor/margin ratio, and pathological surgical margin with staple-line recurrence. Multivariable logistic regression analysis was then conducted. The primary multivariable model was restricted to two clinically relevant variables: tumor/margin ratio, which has previously been associated with local recurrence, and STAS, the main variable of interest in the present study. Multicollinearity was assessed using the variance inflation factor.

To examine whether the risk of local recurrence differed according to STAS status at the same tumor/margin ratio, predicted probabilities of staple-line recurrence were calculated from the primary multivariable logistic regression model (16,17). The logistic regression model was expressed as follows:

logit(p)=β0+β1×Tumor/marginratio+β2×STAS[1]

where p denotes the predicted probability of staple-line recurrence, and STAS was coded as 0 for negative and 1 for positive. The predicted probability was calculated as follows:

p=11+exp[−(β0+β1×Tumor/marginratio+β2×STAS)][2]

The coefficients β0, β1, and β2 were derived from the multivariable logistic regression analysis. Using this model, predicted probabilities of staple-line recurrence were estimated for arbitrary tumor/margin ratios separately for STAS-negative and STAS-positive lesions.

OS and DFS were estimated using the Kaplan-Meier method, and group comparisons were performed using the log-rank test. A two-sided P value <0.05 was considered statistically significant. All statistical analyses were performed using EZR version 1.51, a graphical user interface for R (18).

Results

Clinicopathological characteristics

A total of 70 patients with 70 wedge-resected lesions were included in the analysis (Figure 1). Patient and lesion characteristics according to the presence or absence of staple-line recurrence are summarized in Table 1. The median age was 68 years, and 42 patients were male and 28 were female. The primary tumor originated in the colon in 38 patients and in the rectum in 32 patients. The median disease-free interval from resection of the primary tumor to pulmonary metastasectomy was 13 months. No patient underwent intrathoracic lymph node dissection or sampling during the initial pulmonary metastasectomy; therefore, pathological assessment of intrathoracic lymph node involvement was not available in this cohort.

The median maximum tumor diameter on preoperative CT was 10 mm. The median pathological tumor size was 10 mm, the median pathological surgical margin was 8.5 mm, and the median tumor/margin ratio was 1.4. STAS was identified in 17 lesions (24.3%), and the median farthest STAS distance in STAS-positive lesions was 0.68 mm. The median follow-up period was 60 months, and staple-line recurrence occurred in 14 lesions (20.0%).

Among the 14 staple-line recurrences, 12 lesions (85.7%) were histologically confirmed by repeat resection. The remaining 2 lesions (14.3%) were diagnosed radiologically based on progressive staple-line thickening detected on serial 1-mm-slice chest CT during postoperative follow-up.

Compared with lesions without staple-line recurrence, lesions with recurrence had a shorter pathological surgical margin (median, 7.5 vs. 9.5 mm; P=0.03). Preoperative carcinoembryonic antigen (CEA) level was lower in the recurrence group than in the non-recurrence group (median, 2.20 vs. 3.55 ng/mL; P=0.02). STAS was more frequent in the recurrence group than in the non-recurrence group, although the difference did not reach statistical significance (42.9% vs. 19.6%; P=0.09).

KRAS status was available in 19 of 70 patients. Among these 19 patients, 10 had KRAS mutations and 9 had wild-type KRAS. Staple-line recurrence occurred in 4 of the 10 patients with KRAS mutations and in 3 of the 9 patients with wild-type KRAS, while STAS was observed in 3 patients in each group. Because molecular data and systemic treatment-related variables were not comprehensively available, these variables were not incorporated into the statistical analysis.

Comparison according to STAS status

Preoperative clinicopathological characteristics according to STAS status are shown in Table 2. No significant differences were observed in age, sex, primary tumor site, history of hepatectomy, disease-free interval, number of metastases, laterality of surgery, preoperative CEA level, or tumor size on CT. In this cohort, no routine preoperative clinical factor clearly discriminated between STAS-positive and STAS-negative lesions.

Logistic regression analyses for staple-line recurrence

Factors associated with staple-line recurrence were examined using univariable logistic regression analysis (Table 3). STAS positivity showed a trend toward an increased risk of staple-line recurrence, although the association did not reach statistical significance [odds ratio (OR), 3.07; 95% confidence interval (CI): 0.882–10.7; P=0.08].

In contrast, tumor/margin ratio was significantly associated with staple-line recurrence, with a higher ratio indicating a higher risk of recurrence (OR, 1.38; 95% CI: 1.00–1.91; P=0.049). Pathological surgical margin was also significantly associated with staple-line recurrence, with a longer margin associated with a lower recurrence risk (OR, 0.15; 95% CI: 0.0258–0.834; P=0.03).

In the exploratory multivariable logistic regression model including both tumor/margin ratio and STAS, tumor/margin ratio (OR, 1.52; 95% CI: 1.07–2.15; P=0.02) and STAS (OR, 4.74; 95% CI: 1.20–18.7; P=0.03) remained associated with staple-line recurrence (Table 3). No multicollinearity was observed; the variance inflation factor was 1.12 for both tumor/margin ratio and STAS.

Predicted probability analysis

The fitted logistic regression model used to generate the predicted probability curves was as follows: logit(p) = −2.7469 + 1.5555 × STAS + 0.4178 × tumor/margin ratio, where STAS was coded as 0 for negative and 1 for positive. Model-based predicted probability analysis showed that STAS-positive lesions had a higher predicted probability of staple-line recurrence than STAS-negative lesions at the same tumor/margin ratio (Figure 3). At a tumor/margin ratio of 1.7, which has been proposed in previous studies as a clinically relevant threshold, the predicted probability of recurrence was 11.5% in STAS-negative lesions and 38.2% in STAS-positive lesions. This analysis was intended to illustrate model-based risk differences and was not designed to establish a new margin threshold for STAS-positive lesions.

Figure 3 Predicted probability of staple-line recurrence according to STAS status. Predicted probabilities were calculated from the multivariable logistic regression model including tumor/margin ratio and STAS status. The fitted model was logit(p) = −2.7469 + 1.5555 × STAS + 0.4178 × tumor/margin ratio, with STAS coded as 0 for negative and 1 for positive. STAS-positive lesions showed a higher predicted probability of staple-line recurrence than STAS-negative lesions at the same tumor/margin ratio. STAS, spread through air spaces.

Survival analyses

Kaplan-Meier analysis showed that STAS-positive patients tended to have worse DFS and OS than STAS-negative patients (Figure 4). On log-rank testing, the P values were 0.083 for DFS and 0.059 for OS.

Figure 4 Kaplan-Meier curves for disease-free survival (A) and overall survival (B) according to STAS status. Patients with STAS-positive lesions tended to have worse disease-free survival and overall survival than those with STAS-negative lesions. STAS, spread through air spaces.

Discussion

This study explored the association between STAS and staple-line recurrence after initial wedge resection for colorectal lung metastases. Staple-line recurrence was associated with margin-related factors, including tumor/margin ratio and pathological surgical margin, confirming the importance of local resection adequacy. In addition, STAS remained associated with staple-line recurrence in the exploratory multivariable model after adjustment for tumor/margin ratio, and model-based prediction suggested that STAS-positive lesions may have a higher recurrence risk than STAS-negative lesions at the same tumor/margin ratio. These findings support the concept that staple-line recurrence after wedge resection should be interpreted not only as a consequence of local technical factors, but also in relation to tumor biological features.

The importance of margin adequacy after wedge resection for colorectal lung metastases has been emphasized in previous studies. Shiono et al. proposed a margin distance of 10 mm and a tumor/margin ratio <1.7 as practical benchmarks for reducing surgical margin recurrence (9), while Nelson et al. demonstrated that both tumor size and margin length influence local recurrence risk after wedge resection for colorectal pulmonary metastases (11). In addition, Welter et al. reported the relevance of satellite tumor cells in the resection of colorectal lung metastases, further supporting the biological importance of the peritumoral margin (19). In the present cohort, pathological surgical margin and tumor/margin ratio were associated with staple-line recurrence, which is consistent with these prior observations. These findings reinforce the principle that securing an adequate surgical margin remains a fundamental determinant of local control after wedge resection.

In primary lung cancer, STAS has been reported as a pathological feature associated with recurrence and poor prognosis, particularly after limited resection (12-14). However, colorectal lung metastasis differs from primary lung cancer both clinically and biologically, and whether STAS in colorectal lung metastases is directly linked to staple-line recurrence remains unclear. In pulmonary metastases from colorectal cancer, Takeda-Miyata et al. reported that STAS was associated with poor prognosis and that the farthest STAS distance was an independent risk factor for surgical margin relapse (15). Ma et al. also reported STAS in pulmonary metastasized tumors of various origins (20). Haj Khalaf et al. examined STAS in solitary pulmonary metastases from colorectal cancer (21), and Nakai et al. recently showed that STAS in colorectal lung metastases was associated with local recurrence and reflected morphologic aggressiveness of the primary colorectal tumor (22). Building on these observations, the present study evaluated staple-line recurrence in a cohort limited to initial wedge resections for colorectal lung metastases.

A clinically relevant finding of the present study was that STAS-positive lesions showed a higher model-based recurrence probability than STAS-negative lesions at the same tumor/margin ratio. This suggests that local recurrence risk may not be determined by margin distance alone, but may also be influenced by the biological characteristics of the tumor. Thus, STAS may serve as a pathological marker for identifying lesions at increased risk of staple-line recurrence after wedge resection.

From a clinical perspective, STAS is a postoperative pathological finding and therefore cannot currently be used directly for preoperative procedure selection. Its immediate value may lie in postoperative risk stratification, particularly when the surgical margin is narrow or the tumor/margin ratio is high. The present findings also highlight the need for improved strategies to evaluate local recurrence risk after wedge resection. Future studies should investigate whether STAS can be predicted preoperatively using imaging, PET findings, or molecular markers associated with recurrence after pulmonary metastasectomy for colorectal cancer (23-26), and whether intraoperative margin assessment methods, including cytological approaches or direct tissue-based assessment using novel stapling platforms such as NALS (27), can improve confirmation of margin negativity and reduce staple-line recurrence after pulmonary metastasectomy.

Several limitations should be considered when interpreting these findings. First, this was a single-center retrospective study with a limited number of staple-line recurrence events, and the multivariable analysis was therefore exploratory. Second, because the cohort was restricted to lesions treated by initial wedge resection, the findings may not be generalizable to patients undergoing repeat metastasectomy or anatomical resection. Third, intrathoracic lymph node involvement, molecular background, and systemic treatment-related factors could not be comprehensively assessed, and residual confounding cannot be excluded. Finally, because cytological or direct tissue-based assessment of the stapled margin was not performed, the present study could not determine whether STAS was related to occult margin involvement or represented a broader marker of tumor biology.

Overall, staple-line recurrence after initial wedge resection for colorectal lung metastases was associated with local resection adequacy, represented by tumor/margin ratio and pathological surgical margin. STAS-positive lesions may have a higher local recurrence risk at a given tumor/margin ratio, suggesting that local failure after wedge resection cannot be explained by technical margin factors alone. These findings support a framework in which staple-line recurrence reflects the combined influence of surgical margin adequacy and tumor biology.

Conclusions

In this exploratory cohort of patients who underwent initial wedge resection for colorectal lung metastases, staple-line recurrence was associated with tumor/margin ratio and pathological surgical margin. Importantly, STAS-positive lesions may carry a higher risk of staple-line recurrence even at the same tumor/margin ratio, suggesting that local failure after wedge resection cannot be explained by technical margin factors alone. These findings support a framework in which staple-line recurrence reflects the combined influence of surgical margin adequacy and tumor biology.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1247/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1247/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1247/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-2026-1247/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 Osaka Medical and Pharmaceutical University (No. 2024-068). The requirement for individual written informed consent was waived owing to the retrospective observational design of the study. Information regarding the study was disclosed using an opt-out approach, and patients were given the opportunity to decline participation.

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/.

References

1. Pastorino U, Buyse M, Friedel G, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37-49. [Crossref] [PubMed]
2. Kondo H, Okumura T, Ohde Y, et al. Surgical treatment for metastatic malignancies. Pulmonary metastasis: indications and outcomes. Int J Clin Oncol 2005;10:81-5.
3. Inoue M, Ohta M, Iuchi K, et al. Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 2004;78:238-44. [Crossref] [PubMed]
4. Shiono S, Okumura T, Boku N, et al. Outcomes of segmentectomy and wedge resection for pulmonary metastases from colorectal cancer. Eur J Cardiothorac Surg 2017;51:504-10. [Crossref] [PubMed]
5. Dickinson KJ, Blackmon SH. Results of Pulmonary Resection: Colorectal Carcinoma. Thorac Surg Clin 2016;26:41-7. [Crossref] [PubMed]
6. Prisciandaro E, Ceulemans LJ, Van Raemdonck DE, et al. Impact of the extent of lung resection on postoperative outcomes of pulmonary metastasectomy for colorectal cancer metastases: an exploratory systematic review. J Thorac Dis 2022;14:2677-88. [Crossref] [PubMed]
7. Shiono S, Ishii G, Nagai K, et al. Predictive factors for local recurrence of resected colorectal lung metastases. Ann Thorac Surg 2005;80:1040-5. [Crossref] [PubMed]
8. Chung JH, Lee SH, Yi E, et al. Impact of resection margin length and tumor depth on the local recurrence after thoracoscopic pulmonary wedge resection of a single colorectal metastasis. J Thorac Dis 2019;11:1879-87. [Crossref] [PubMed]
9. Shiono S, Matsutani N, Hashimoto H, et al. Prospective study of recurrence at the surgical margin after wedge resection of pulmonary metastases. Gen Thorac Cardiovasc Surg 2021;69:950-9. [Crossref] [PubMed]
10. Higashiyama M, Kodama K, Takami K, et al. Intraoperative lavage cytologic analysis of surgical margins as a predictor of local recurrence in pulmonary metastasectomy. Arch Surg 2002;137:469-74. [Crossref] [PubMed]
11. Nelson DB, Tayob N, Mitchell KG, et al. Surgical margins and risk of local recurrence after wedge resection of colorectal pulmonary metastases. J Thorac Cardiovasc Surg 2019;157:1648-55. [Crossref] [PubMed]
12. Kadota K, Nitadori JI, Sima CS, et al. Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas. J Thorac Oncol 2015;10:806-14. [Crossref] [PubMed]
13. Warth A, Muley T, Kossakowski CA, et al. Prognostic Impact of Intra-alveolar Tumor Spread in Pulmonary Adenocarcinoma. Am J Surg Pathol 2015;39:793-801. [Crossref] [PubMed]
14. Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma. Interact Cardiovasc Thorac Surg 2016;23:567-72. [Crossref] [PubMed]
15. Takeda-Miyata N, Konishi E, Tanaka T, et al. Prognostic significance of spread through air spaces in pulmonary metastases from colorectal cancer. Lung Cancer 2020;149:61-7. [Crossref] [PubMed]
16. Royston P, Moons KG, Altman DG, et al. Prognosis and prognostic research: Developing a prognostic model. BMJ 2009;338:b604. [Crossref] [PubMed]
17. Muller CJ, MacLehose RF. Estimating predicted probabilities from logistic regression: different methods correspond to different target populations. Int J Epidemiol 2014;43:962-70. [Crossref] [PubMed]
18. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 2013;48:452-8. [Crossref] [PubMed]
19. Welter S, Theegarten D, Trarbach T, et al. Safety distance in the resection of colorectal lung metastases: a prospective evaluation of satellite tumor cells with immunohistochemistry. J Thorac Cardiovasc Surg 2011;141:1218-22. [Crossref] [PubMed]
20. Ma Y, Zhang Y, Li H, et al. Spread through air spaces is a common phenomenon of pulmonary metastasized tumours regardless of origins. Eur J Cardiothorac Surg 2022;61:1242-8. [Crossref] [PubMed]
21. Haj Khalaf MA, Sirbu H, Hartmann A, et al. Spread through Air Spaces (STAS) in Solitary Pulmonary Metastases from Colorectal Cancer (CRC). Thorac Cardiovasc Surg 2023;71:138-44. [Crossref] [PubMed]
22. Nakai T, Morita S, Kurebayashi Y, et al. Spread Through Air Spaces in Colorectal Lung Metastases Signals Local Recurrenece and Reflects Morphologic Aggressiveness of the Primary Tumor. Pathol Int 2026;76:e70107. [Crossref] [PubMed]
23. Schweiger T, Hegedüs B, Nikolowsky C, et al. EGFR, BRAF and KRAS status in patients undergoing pulmonary metastasectomy from primary colorectal carcinoma: a prospective follow-up study. Ann Surg Oncol 2014;21:946-54. [Crossref] [PubMed]
24. Ghidini M, Personeni N, Bozzarelli S, et al. KRAS mutation in lung metastases from colorectal cancer: prognostic implications. Cancer Med 2016;5:256-64. [Crossref] [PubMed]
25. Corsini EM, Mitchell KG, Mehran RJ, et al. Colorectal cancer mutations are associated with survival and recurrence after pulmonary metastasectomy. J Surg Oncol 2019;120:729-35. [Crossref] [PubMed]
26. Huang J, Zang Q, Wen Y, et al. Prognostic value of KRAS mutation in patients undergoing pulmonary metastasectomy for colorectal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2021;160:103308. [Crossref] [PubMed]
27. Kang SK, Bok JS, Cho HJ, et al. Novel Asymmetrical Linear Stapler (NALS) for pathologic evaluation of true resection margin tissue. J Thorac Dis 2018;10:S1631-6. [Crossref] [PubMed]