Impact of bronchial anastomosis wrapping on outcomes following sleeve lobectomy

Introduction

Non-small cell lung cancer (NSCLC) is one of the cancers with high incidence and the leading cause of cancer-related deaths worldwide (1). Surgery remains the cornerstone of treatment for early-stage disease, with sleeve lobectomy representing a critical technique for centrally located tumors, particularly those involving the main airways, which was first introduced by Price-Thomas in 1947 for treating carcinoid tumors (2). This surgical technique is crucial for resecting central lung cancers, especially those located near the main airways, as it allows tumor resection while preserving lung function. Compared to pneumonectomy, it offers particular advantages for elderly patients, particularly those with compromised pulmonary function (3). Bronchopleural fistula (BPF) is a rare but severe complication following pneumonectomy and sleeve lobectomy, often endangering the patient’s life (4). To reduce the incidence of BPF after lung transplantation, some surgeons have proposed using omentum or internal mammary artery flaps to wrap the anastomosis, thereby reducing the risk of BPF and improving survival rates (5). Similarly, some researchers (6) suggested that using autologous pericardium, pleura, intercostal muscle flaps, or mediastinal fat to wrap the bronchial anastomosis in sleeve lobectomy may reduce the occurrence of anastomotic complications. Angiogenesis is a critical event in the wound healing process. Preclinical study (7) suggested that an autologous pericardium pad could produce the angiogenic cytokine within 7 days after the primary culture. At the same time, Matsumoto et al. (8) reported that autologous pericardial tissue could act as a sealant for preventing air leakage. Among these, autologous pericardium is particularly favored for its biocompatibility and angiogenic potential. However, some researchers, such as Storelli et al. (9), believed that leaving the bronchial anastomosis unwrapped may also be a safe approach in sleeve lobectomy. The debate regarding whether to wrap or not remains ongoing. Therefore, this study aimed to investigate whether wrapping the bronchial anastomosis influences perioperative outcomes and 5-year survival. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1670/rc).

Methods

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Institutional Review Board of The First Affiliated Hospital of Chongqing Medical University (approval No. K2024-158-01). The requirement for informed consent was waived due to the retrospective nature of the study. This study retrospectively analyzed 99 patients who underwent sleeve lobectomy for pulmonary tumors from January 2012 to December 2017. Patients meeting the subsequent criteria were excluded from our study: (I) those with incomplete clinical information; (II) patients whose pathology was not NSCLC. According to the exclusion criteria, we excluded 8 patients, including 4 cases of small cell lung cancer (SCLC), 2 cases of bronchial adenoma, 1 case of neuroendocrine neoplasms (NENs), and 1 case of a benign lesion. A total of 91 patients were finally included in the analysis and divided into two groups: Group A, consisting of 29 patients who did not undergo bronchial anastomosis wrapping, and Group B, consisting of 62 patients who underwent wrapping with autologous pericardial tissue (Figure 1). Clinical data were retrospectively collected from the hospital’s electronic medical record system, operative notes, and postoperative follow-up documentation. Collected data included age, sex, smoking history, surgical site, histological type, tumor stage, neoadjuvant therapy, and preoperative albumin levels. Charlson comorbidity index (10) was used to evaluate preoperative comorbidities and postoperative complications were classified according to the Clavien-Dindo classification (11). Perioperative-related indicators included postoperative complications, duration of chest tube drainage, hospital length of stay and intensive care unit (ICU) length of stay, frequency of BPF, 30-day mortality, and 90-day mortality. Long-term outcome measures included the 5-year survival rate. The follow-up period was defined as the time from the date of surgery to the date of patient death or the last observation. All variables were assessed using standardized definitions and recorded by trained clinicians. For patients in both the wrapping and non-wrapping groups, the methods of data collection and assessment were consistent to ensure comparability between groups. For patients without regular follow-up, data were collected through telephone contact with the patients or their family members.

Figure 1 Flow chart of patient selection. Group A, no wrapping; group B, bronchial wrapping. NENs, neuroendocrine neoplasms; NSCLC, non-small cell lung cancer; PSM, propensity score-matched; SCLC, small cell lung cancer.

Consistent surgical protocols and postoperative care pathways were applied across groups to reduce performance bias. All patients were intubated with a double-lumen endotracheal tube under bronchoscopic vision. A standard posterolateral thoracotomy was performed to access the thoracic cavity. The pulmonary vein, pulmonary artery, and bronchus were routinely mobilized and divided. A systemic lymph node dissection was carried out in all patients, and intraoperative frozen sections were obtained to ensure negative resection margins. All resections were R0. An end-to-end bronchial anastomosis was performed using continuous 3-0 polydioxanone sutures (PDS). The bronchial anastomosis was then wrapped with autologous pericardial tissue. It was performed using a pedicled pericardial flap harvested from the anterolateral pericardium near the phrenic nerve, care being taken not to injure the underlying heart or pericardiophrenic nerve and vessels. The flap was attached caplike over the bronchial stump with numerous single-attress stitches of 4-0 polydioxanone (PDS). Care was taken to avoid twisting or compression of the anastomotic site and to ensure adequate blood supply and drainage of the pericardial flap. The thoracotomy was closed in layers. Immediately after completion of the bronchial anastomosis, a fiberoptic bronchoscopy was performed to assess anastomotic patency and integrity. All patients were transferred to the ICU and mechanically ventilated.

Statistical analysis

Statistical analysis was performed using SPSS version 25.0 (IBM-SPSS Inc., Armonk, NY). Quantitative variables were assessed for distribution using the Shapiro-Wilk test. Continuous variables were presented as means ± standard deviation or median with interquartile range (IQR) and analyzed using the independent t-tests or Mann-Whitney U test. For further analysis, some continuous variables were categorized into clinically meaningful groups. Categorical variables were presented as frequency (%) and compared using the Pearson χ² test or Fisher exact test. Overall survival (OS) was estimated using the Kaplan-Meier method, and survival comparisons between groups was performed using the log-rank test. We propensity score-matched (PSM) the group A and group B on their age, sex, smoking history, pack-years, albumin, Charlson Comorbidity Index, neoadjuvant therapy, lobectomy, pathological tumor (pT) stage, pathological node (pN) stage, tumor-node-metastasis (TNM) stage and histology. For the matching, we used the nearest neighbor method with a 1-to-1 ratio, a caliper of 0.05-fold standard deviation, and an order going from largest to smallest propensity score without replacement. After matching, 20 patients were included in each group. A P value <0.05 was considered statistically significant. There was no missing data for any of the key variables included in the analysis

Results

There were no differences in general characteristics (Table 1) between the two groups. Group B had a higher rate of pathological N1 and N2 metastases (N1, 37.1% vs. 3.45%; N2, 30.65% vs. 27.59%, P=0.001), and were at a more advanced pathological TNM stage (stage II, 40.32% vs. 31.03%; stage III, 48.39% vs. 34.48%, P=0.02) (Table 2). Differences between the groups were equalized after 1:1 propensity score matching, which produced the matched cohort, consisting of 20 patients for each group. The general characteristics and surgical characteristics of the study cohort are presented in Tables 3,4. There were no significant differences in operative time (236.14±41.34 vs. 242.90±41.75 min, P=0.47), intraoperative bleeding (251.72±185.88 vs. 283.87±204.41 mL, P=0.47), intraoperative transfusion (yes, 3.45% vs. 3.23%, P>0.99), perioperative transfusion (yes, 17.24% vs. 9.68%, P=0.49), mechanical ventilation (184.97±186.20 vs. 285.87±402.89 min, P=0.20), ICU stay (3.41±1.09 vs. 4.15±2.88 days, P=0.19), chest tube drainage (8.72±4.13 vs. 8.06±3.57 days, P=0.44), BPF morbidity (yes, 3.45% vs. 4.84%, P>0.99), postoperative albumin (31.17±4.03 vs. 30.77±4.05 g/L, P=0.66). Of the 29 patients in group A, 6 experienced postoperative complications (20.69%). According to the Clavien-Dindo classification, there were 5 patients who had grade II (17.24%) and 1 patient who had grade V (3.45%). In Group B, 11 experienced complications (17.74%). According to the Clavien-Dindo classification, there were 6 patients who had grade II (9.68%), 1 grade III (1.61%) and 4 grade V (6.45%) (Table 5). But the results were not statistically significant between groups (P=0.73). In group A, the 30-day mortality and the 90-day mortality rates were 3.45% (1 patient). In group B, the 30-day mortality rate was 9.68% (6 patients) and the 90-day mortality rate was 12.90% (8 patients). In group A, one patient succumbed on postoperative day 25 due to pulmonary infection and respiratory failure. In group B, three patients died from respiratory failure and pulmonary infection on postoperative days 7, 10, and 11, respectively. Additionally, two patients underwent total pneumonectomy following BPF, with multiple organ failure leading to death on postoperative days 7 and 10. Another patient in group B died on postoperative day 20 due to anastomotic stricture and pulmonary infection. In terms of long-term prognosis, the 5-year survival rate for group A was 55.17%, compared to 48.39% for group B. The median follow-up time was 60 months in both groups. A total of 55.17% of patients in group A and 48.39% of patients in group B were followed for at least 60 months.

The OS rate within the 5-year survival rate was slightly higher in group A than in group B, but the results were not statistically significant between groups (P=0.79). Survival rates in group A stabilized within 2 years post-surgery, while survival rates in group B stabilized after 3 years post-surgery (Figure 2). Follow-up period ranged from 1 to 60 months, and was complete for 91 patients (100%). After PSM, there remained no statistically significant differences between the two groups in 30-day mortality, 90-day mortality, or 5-year survival rate (40.0% vs. 35.0%, P=0.58) (Table 6 and Figure 3).

Figure 2 Survival curve of patients in group A and group B. Group A, no wrapping; group B, bronchial wrapping.

Figure 3 Survival curve of patients in group A and group B after PSM. Group A, no wrapping; group B, bronchial wrapping. PSM, propensity score-matched.

Discussion

This study systematically evaluates the application of autologous pericardial tissue wrapping for bronchial anastomosis in sleeve lobectomy. With the advancement of surgical techniques, sleeve lobectomy has gradually replaced pneumonectomy and gained more attention and development. However, anastomotic-related complications, particularly BPF, remain one of the major issues affecting patients’ surgical outcomes and quality of life. In our study, there were no significant differences in the surgical characteristics between the two groups, except that group B had a higher rate of lymph node metastasis (N1–2) (P=0.001) and advanced pathological TNM stage (II–III) (P=0.02). This difference might reflect the preoperative tendency of surgeons to opt for an anastomotic protection in high-risk patients. This was consistent with Shahrokh et al.’s study (12), which found that the use of autologous pericardial tissue to reinforce the anastomosis effectively reduces the incidence of BPF in high-risk patients. And, there were no significant differences in intraoperative factors such as operative time (P=0.47), intraoperative blood loss (P=0.47) and intraoperative transfusion (P>0.99). This suggested that the feasibility and safety of the surgical procedures were comparable between the two groups, and the use of autologous pericardial tissue did not significantly increase intraoperative complexity or risk. The overall complication rate in group B and the incidence of severe complications (Clavien-Dindo II–IV) were higher compared to group A, although these differences did not reach statistical significance. These results might suggest that the autologous pericardial tissue wrapping technique did not offer a clear advantage over traditional methods in protecting the anastomosis postoperatively, despite the theoretical potential of autologous pericardial tissue to produce angiogenic factors, stimulate angiogenesis, and promote anastomotic healing, thereby preventing complications (7). It was worth noting that the 30- and 90-day mortality rates in group B were higher than those in group A, at 9.68% and 12.90%, respectively, compared to 3.45% and 3.45% in group A. However, these differences did not reach statistical significance (P=0.79). The main causes of death in group B included respiratory failure, infection, and BPF, which might be associated with the advanced pathological TNM stage in group B. A study has shown (13) that postoperative complications such as lung infection, respiratory failure, and multiple organ failure were often associated with the biological characteristics of advanced tumors. In patients with advanced tumors, immune function was suppressed, making them more susceptible to postoperative infections. These patients often required prolonged mechanical ventilation and extended ICU stays, which further lengthen hospitalization and increase perioperative mortality (14,15). After matching to eliminate the influence of lymph node status and pathological stage, there remained no statistically significant differences in 30- or 90-day mortality between the two groups, indicating that bronchial anastomotic wrapping has no apparent benefit on short-term outcomes. In terms of long-term prognosis, the 5-year survival rates for group A and group B were 55.17% and 48.39%, respectively. Although group A showed a slightly higher survival rate, there was no significant statistical difference (P=0.79), indicating that the wrapping of the anastomosis might not be the sole determining factor affecting the long-term survival rate of patients. Survival analysis was included not to imply a causal link between wrapping and survival, but to confirm that omission of wrapping does not compromise long-term oncologic outcomes. There were also reports (16) suggesting that bronchoalveolar lavage could reduce the occurrence of pulmonary complications. Furthermore, the incidence of BPF was similar between the two groups. This result was consistent with some studies (17) regarding the incidence of BPF after sleeve lobectomy. However, group B experienced two deaths attributable to BPF and one death due to anastomotic stricture, whereas no such events occurred in group A. This observation partially contradicts the findings of Rea et al. (18), who reported that wrapping might reduce the risk of BPF. In patients with advanced tumors, particularly those receiving neoadjuvant therapy, the bronchial microvasculature is often compromised (19). Tedder et al. (17) proposed that the benefit of wrapping the anastomosis lies not in improving perfusion, but in providing a physical barrier to prevent BPF. Considering that pericardial tissue might have different physiological characteristics from the trachea, angiogenesis could be hindered, leading to ischemia and affecting the healing of the tracheal anastomosis. Additionally, Deeb et al. (20) reported a case of ectopic ossification following the use of a pedicled intercostal muscle flap, leading to severe bronchial stenosis, which ultimately required a pneumonectomy. Additionally, prior studies have also suggested (21) that wrapping the anastomosis could lead to the formation of stubborn adhesions between the bronchus and adjacent structures. Consistent with previous reports (22) using intercostal muscle or pericardial fat, our findings suggest that omission of wrapping does not increase anastomotic or postoperative complications, supporting selective rather than routine use. Based on Mehran et al.’s study (23), we recommend prioritizing systemic treatment, such as neoadjuvant therapy, for patients with N2 metastasis or advanced pathological TNM stage, rather than relying on anastomosis wrapping techniques. There are certain limitations in this study. The single-center, retrospective design and limited sample size restrict the generalizability of our findings. Larger multicenter prospective studies are needed to validate these results. In addition, the omission of diabetes and prior steroid use from the baseline characteristics represents another limitation of this study. Future research should include more comprehensive demographic and clinical variables. Additionally, utilizing multi-center studies with larger sample sizes will be essential to investigate how to optimize surgical techniques and postoperative management across different patient populations in order to improve short-term prognosis and long-term survival rates.

Conclusions

In conclusion, we report that there were no differences in short-term prognosis or long-term survival rates between patients who underwent autologous pericardial reinforcement of the bronchial anastomosis and those who did not, which also aligns with previous reports. This cohort demonstrated no clear benefit from routine coverage. Therefore, uniform coverage is not supported, but individualized coverage based on case selection should continue to be considered.

Acknowledgments

This abstract was presented as an oral presentation on May 15, 2025, at the 33rd Annual Meeting of the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS), held in Singapore.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1670/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1670/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1670/prf

Funding: This work was supported by the Chongqing Technology Innovation and Application Development Project (No. CSTB2022TIAD-KPX004).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1670/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 Ethics Board of The First Affiliated Hospital of Chongqing Medical University (No. K2024-158-01) and individual consent for this retrospective analysis was waived.

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. Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer. Lancet 2021;398:535-54. [Crossref] [PubMed]
2. THOMAS CP. Conservative resection of the bronchial tree. J R Coll Surg Edinb 1956;1:169-86.
3. Chen J, Soultanis KM, Sun F, et al. Outcomes of sleeve lobectomy versus pneumonectomy: A propensity score-matched study. J Thorac Cardiovasc Surg 2021;162:1619-1628.e4. [Crossref] [PubMed]
4. Farkas EA, Detterbeck FC. Airway complications after pulmonary resection. Thorac Surg Clin 2006;16:243-51. [Crossref] [PubMed]
5. Khaghani A, Tadjkarimi S, al-Kattan K, et al. Wrapping the anastomosis with omentum or an internal mammary artery pedicle does not improve bronchial healing after single lung transplantation: results of a randomized clinical trial. J Heart Lung Transplant 1994;13:767-73.
6. Rendina EA, Venuta F, Ciriaco P, et al. Bronchovascular sleeve resection. Technique, perioperative management, prevention, and treatment of complications. J Thorac Cardiovasc Surg 1993;106:73-9.
7. Shoji F, Yano T, Miura N, et al. Pericardial fat pad tissue produces angiogenic factors for healing the bronchial stump. Interact Cardiovasc Thorac Surg 2011;13:271-5. [Crossref] [PubMed]
8. Matsumoto I, Ohta Y, Oda M, et al. Free pericardial fat pads can act as sealant for preventing alveolar air leaks. Ann Thorac Surg 2005;80:2321-4. [Crossref] [PubMed]
9. Storelli E, Tutic M, Kestenholz P, et al. Sleeve resections with unprotected bronchial anastomoses are safe even after neoadjuvant therapy. Eur J Cardiothorac Surg 2012;42:77-81. [Crossref] [PubMed]
10. Charlson ME, Carrozzino D, Guidi J, et al. Charlson Comorbidity Index: A Critical Review of Clinimetric Properties. Psychother Psychosom 2022;91:8-35. [Crossref] [PubMed]
11. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009;250:187-96. [Crossref] [PubMed]
12. Taghavi S, Marta GM, Lang G, et al. Bronchial stump coverage with a pedicled pericardial flap: an effective method for prevention of postpneumonectomy bronchopleural fistula. Ann Thorac Surg 2005;79:284-8. [Crossref] [PubMed]
13. Li X, Li Q, Yang F, et al. Neoadjuvant therapy does not increase postoperative morbidity of sleeve lobectomy in locally advanced non-small cell lung cancer. J Thorac Cardiovasc Surg 2023;166:1234-1244.e13. [Crossref] [PubMed]
14. Fridman WH, Pagès F, Sautès-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012;12:298-306. [Crossref] [PubMed]
15. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99. [Crossref] [PubMed]
16. Burfeind WR Jr, D'Amico TA, Toloza EM, et al. Low morbidity and mortality for bronchoplastic procedures with and without induction therapy. Ann Thorac Surg 2005;80:418-21; discussion 422. [Crossref] [PubMed]
17. Tedder M, Anstadt MP, Tedder SD, et al. Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy. Ann Thorac Surg 1992;54:387-91. [Crossref] [PubMed]
18. Rea F, Marulli G, Schiavon M, et al. A quarter of a century experience with sleeve lobectomy for non-small cell lung cancer. Eur J Cardiothorac Surg 2008;34:488-92; discussion 492. [Crossref] [PubMed]
19. Yamamoto R, Tada H, Kishi A, et al. Effects of preoperative chemotherapy and radiation therapy on human bronchial blood flow. J Thorac Cardiovasc Surg 2000;119:939-45. [Crossref] [PubMed]
20. Deeb ME, Sterman DH, Shrager JB, et al. Bronchial anastomotic stricutre caused by ossification of an intercostal muscle flap. Ann Thorac Surg 2001;71:1700-2. [Crossref] [PubMed]
21. Campisi A, Ciarrocchi AP, Congiu S, et al. Sleeve Lobectomy: To Wrap or Not to Wrap the Bronchial Anastomosis? Ann Thorac Surg 2022;113:250-5. [Crossref] [PubMed]
22. Li X, Li Q, Yang F, et al. Survival Outcomes of Neoadjuvant Therapy Followed by Sleeve Lobectomy in Non-Small Cell Lung Cancer. Ann Thorac Surg 2025;119:1185-95. [Crossref] [PubMed]
23. Mehran RJ, Deslauriers J, Piraux M, et al. Survival related to nodal status after sleeve resection for lung cancer. J Thorac Cardiovasc Surg 1994;107:576-82; discussion 582-3.