Evaluation of Progel in minimally invasive segmentectomy: a multicentric retrospective series

Introduction

Lung cancer is the leading cause of cancer-death worldwide (1). The gold standard treatment for early-stage lung cancer is minimally invasive anatomical lung resection (2,3). However, in recent years, the screening program has increased the detection of stage I lung cancer. Anatomical segmentectomy has since been widely used to remove small peripheral lesions less than 2 cm. The recent findings from the JCOG-0802 randomized trial have confirmed that anatomic segmentectomy is associated with at least similar if not superior overall survival compared to lobectomy for solid or partly solid early-stage lung cancer (4). However, segmentectomy is associated with an increased rate of prolonged air leak (PAL) compared to lobectomy (4-6).

PAL, usually defined as greater than 5 days, is a frequent occurrence after pulmonary resection, with a reported incidence of approximately 15% (7-9). Although usually not life-threatening, they are estimated to extend hospitalization by 5 to 6 days (7-9), and their management is one of the most significant causes of protracted hospital stay and increased cost (10). In addition, patients with PAL have a higher risk of developing pneumonia, empyema and ICU readmission (11-16). Therefore, intraoperative control of air leaks is imperative to reduce morbidity, length of hospitalization, and health care cost.

Over the years, several products have been developed and tested in order to reduce air leak rates. Fibrin-based sealants have been reported to be ineffective in controlling air leaks by several authors (10-13). Protein-based polymers may be effective in controlling air leaks, but they are inflexible and so they do not allow the expansion and contraction of the lung. Finally, synthetic materials have been found to be effective in sealing intraoperative air leaks, but their use might be laborious, since they require the application of several layers and light activation in order to polymerize.

Subsequently, a polymeric biodegradable sealant that did not require light activation was developed by combining a polyethylene glycol-based cross linker, functionalized with succinate groups [PEG-(SS)₂], with recombinant human albumin (rHA), just prior to usage (Progel^TM Platinum, BD, Switzerland). Once mixed, the sealant polymerizes to form a clear, flexible hydro-gel matrix that adheres to the lung tissue. After application, the material forms a flexible seal over the surface of the air leak that can endure 30 mmHg air pressure. The material is biodegradable and is completely reabsorbed from the lung surface by 1 month after surgery (14).

Despite data showing the efficacy of Progel^TM Platinum in reducing intraoperative and postoperative air leaks following open and minimally-invasive lobectomy, there are little data on its use during minimally invasive approaches after a segmentectomy to prevent PAL (4-6). The aim of this multicentre, retrospective study was to evaluate the safety and efficacy of Progel^TM Platinum for preventing the occurrence of PALs following a minimally-invasive segmentectomy. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1054/rc).

Methods

Patients selection

All consecutive patients from retrospective databases who underwent a Robotic-assisted [robot-assisted thoracic surgery (RATS)] and video-assisted [video-assisted thoracic surgery (VATS)] anatomical segmentectomy for stage I lung cancer at two high volume centres (Guy’s and St Thomas’ NHS Foundation Trust, London, UK and Hôpital Saint Joseph, Marseille, France) between January 2018 and September 2022 were included in this study. Exclusion criteria were known sensitivity to human albumin, post-operative assisted mechanical ventilation, open approach, and procedures other than segmentectomy, namely pneumonectomy, lobectomy, wedge resection and chest wall resection.

Patients were divided into two groups according to whether Progel^TM Platinum was used or not: sealant group (SG) and the control group (CG). All the patients underwent an anatomical segmentectomy before 2021 and did not receive the air sealant, while patients operated on since 2021 received the sealant in any case an air-leak was detected at the end of the procedure.

Patients were characterized according to demographic variables, including age, and sex; clinical variables, comorbidities, body mass index (BMI), forced expiratory volume in 1 second (FEV1), previous chemotherapy or radiotherapy to the chest; surgical variables, including surgical approach, segmentectomy type, and presence of adhesions were evaluated. The presence of adhesions was defined as pleural adhesions occupying more than 30% of the pleural cavity.

Simple segmentectomy was defined as segmental resection that creates one, linear intersegmental plane, with a relatively easier procedure, such as resection of the right or left segment 6, left superior, or lingular segments. Complex segmentectomy was defined as a segmentectomy that creates several, or intricate intersegmental planes, that is segmentectomy other than simple segmentectomy (17-20).

Postoperative PALs were measured from the day of surgery until the chest tube was removed and were defined as greater than 5 days.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was an audit project, approved by the Institutional Ethics Board of Guy’s and St Thomas NHS Foundation Trust (No. 14012). All participating centres were informed and agreed the study. Individual consent for this retrospective analysis was waived.

Outcomes

Primary outcome measure was the incidence of PAL. Secondary measures were length of hospital stay (LOS), length of chest drain (LOD), postoperative complication rate, 30-day readmission rate and 90-day mortality.

Surgical technique

All the surgical procedures were performed by one board-certified surgeons in each centre. RATS segmentectomies were performed using a Da Vinci Xi Surgical Robot (Intuitive Surgical, Inc., Santa Clara, CA, USA) via 4 robotic ports (two 8-mm ports and two 12-mm ports) plus an additional port for bedside assistance and specimen retrieval. CO₂ at a pressure of 6–8 cmH₂O was used to perform the robotic procedure. Regarding VATS segmentectomies, we used a 3-port anterior approach according to the Copenhagen technique, as reported by Hansen and Petersen (21).

The intersegmental division was performed using monopolar energy devices to open the fissure and then using staplers to complete the intersegmental plan.

The sealant was applied intraoperatively to any area where the lung was intervened upon, including the remaining lung, staple lines, and raw pulmonary surface in any case where an air leak was detected at the end of the case. Progel^TM Platinum was applied on deflated lung, on dry surface, for at least 2 minutes before re-expanding the lung.

Statistical analysis

The characteristics of this study’s population are reported using numbers and percentages or median and interquartile range (IQR). Between-group differences were evaluated using the Chi-squared test for categorical variables and the Wilcoxon-Mann-Whitney test for continuous variables.

All statistical tests were two-tailed, and P values <0.05 were considered statistically significant. All analyses were carried out using GraphPad Prism version 9.5.1 (528).

Results

Patients’ characteristics

A total of 181 patients were included in the study, 90 patients in the SG and 91 in the CG. The median age of the entire population was 69 years (IQR: 12 years), and 62% (n=112) were women; 31% and 34% of the patients in the SG and CG, respectively, had chronic obstructive pulmonary disease (COPD); the median FEV1 was 95% (IQR: 24%) and 89% (IQR: 34%) in the SG and CG, respectively.

Within the SG, 2.2% (n=2) of patients received neoadjuvant therapy, while in the CG, 3.3% (n=3) received neoadjuvant therapy. Patient demographics, comorbidities, and surgical variables are listed in Table 1.

There were no significant differences between the groups in terms of demographic characteristics, comorbidities, neoadjuvant therapy, FEV1, patients with BMI <25.5 kg/m², or surgical approach and procedure. In the SG, a significantly higher number of patients had adhesions compared to the CG (28% vs. 11%; P=0.004).

Primary outcomes

PAL was observed in only 5.5% (n =5) of patients in the SG and in 12.1% (n =11) of patients in the CG; however, this difference was not statistically significant (P=0.19) (Figure 1). Interestingly, in the CG, there was a statistically significant difference in the rate of PALs following a simple and complex segmentectomy (2.8% vs. 18.2%; P=0.03). However, in the SG the rate of PAL did not differ between the two types of segmentectomies (6.1% vs. 5.3%; P=0.87) (Table 2, Figure 2).

Figure 1 Rate of prolonged air leaks. PAL, prolonged air leak.

Figure 2 Rate of PALs following complex and simple segmentectomies. (A) Rate of PAL in sealant group; (B) rate of PALs in control group. PAL, prolonged air leak.

Secondary outcomes

The mean LOS was significantly reduced in the SG (4.0±2.8 days) compared to the CG (7.0±5.0 days) (P<0.001) (Figure 3A, Table 3).

Figure 3 Secondary outcomes. (A) Length of hospitalization; (B) length of chest drain. SD, standard deviation.

The mean duration of chest tubes was double the days in the CG compared to the SG (3.8. vs. 2.1 days; P=0.01) (Figure 3B, Table 3). This was due to the fact that more patients in the CG compared to the SG had an air leak and kept the drain in situ for more than 2 days [44% (n=40) vs. 30% (n=27)] (Figure 4, Table 3).

Figure 4 Duration of chest drain.

Post-operative morbidity and mortality of the two cohorts are listed in Table 3. There was a significant difference in the rate of complications overall between the SG and the CG (27.8% vs. 38.5%, respectively; P=0.02); furthermore, looking at the rate of single complications, in the CG significantly more patients developed a chest infection compared with the SG (2.2% vs. 10.9%; P=0.02); this difference may be related to prolonged chest drain stay, which could cause more pain, poor cough and limited mobilization.

There were no significant differences in readmissions between the groups (P=0.25), and no 90-day mortality in either group. In the SG, 1 patient was readmitted for pneumothorax, and the other for a pleural effusion, while in the CG, 2 patients were readmitted for a pleural effusion, other 2 for a pneumothorax and 1 patient was readmitted for having developed a major surgical emphysema.

Discussion

In recent years, the role of segmentectomy in thoracic surgery has become more relevant due to early detection of smaller and peripheral lesions. The JCOG-0802 randomized trial has proved that anatomic segmentectomy is associated with at least similar if not superior long-term survival compared to lobectomy for solid or partly solid early-stage lung cancer less than 2 cm. Those results showed segmentectomy to be an effective radical treatment for early-stage lung cancer, not only reserved to patients with compromised pulmonary function (4).

However, some studies suggested that segmentectomies might be associated with a higher risk of PALs; in the JCOG-0802 trial, there was a higher incidence of PAL in the segmentectomy arm compared to the lobectomy arm (6.5% vs. 3.8%; P=0.04) (4). This might be due to the fact that segmentectomy usually requires a deeper dissection into the lung parenchyma, especially in complex segmentectomies, where the intersegmental planes are often three-dimensional and there might be the necessity of multiple staple lines crossing different planes. This may generate an increased parenchymal tension on re-expansion of the lung, which may lead to parenchymal tearing along the staple lines. Suzuki et al. (5) in their report of the JCOG randomized trial found that 70% of patients in the segmentectomy arm who had PAL after surgery had undergone a complex segmentectomy. Gooseman and colleagues in their retrospective study found that the incidence of PAL after complex segmentectomies was 53% higher compared to that after simple segmentectomies (21% vs. 15%, P=0.13) (6).

In our study, almost double the patients in the CG had a post-operative PAL compared to the group where the sealant was used (12.1% vs. 5.5%), even though this difference was not statistically significant. Interestingly, in the CG there was a significant difference in the rate of PAL following simple and complex segmentectomies (2.8% vs. 18.2%; P=0.028), whereas in the SG this difference disappeared, with 6.1% of the patients with PAL after a simple segmentectomy and 5.3% of patients with PAL following a complex segmentectomy (P=0.874), showing its efficacy. Our results are in line with the recent literature: many studies proved Progel^TM to be effective in reducing air-leaks after a pulmonary resection. Allen et al., in their multicentre prospective randomized trial, showed that intraoperative air leaks were sealed in 77% of the patients undergone an open lung resection where the sealant was used to repair the leak, compared to only 16% of the patients where conventional methods were used to repair it (P<0.001) (22). Park and colleagues did a multicentre prospective single-arm trial where they demonstrated that the application of Progel^TM during a minimally invasive lung resection was effective to seal the majority of intraoperative air leaks (81%), and that 49% of the patients were free of air leaks throughout the entire post-operative study period (23).

PALs after surgery might lead to a prolonged hospitalization, exposing the patients to a higher risk of complications (7-16). Wright et al. in their study showed that PALs are the second reason for failure to discharge by the target day (10). Liberman et al. (15), in their retrospective case-control study, observed that patients who had a post-operative PAL were more likely to have complications, especially pneumonia (13.3% vs. 4.9%; P=0.014), a prolonged LOS (14.2 vs. 7.1 days; P<0.001) and a longer LOD (11.5 vs. 3.4 days; P<0.001) compared to patients with no PALs. Brunelli and colleagues showed that people with PAL had a higher rate of empyema compared to patients without air leak (8.2% vs. 0%; P=0.01) (13). Similarly, in our series, patients in the CG had a significantly higher complication rate compared to the SG (38.5% vs. 27.8%; P=0.02), particularly looking at the chest infection rate, which was almost 5 times higher in the CG than in the SG (10.9% vs. 2.2%; P=0.2); this result might be related to a prolonged chest drain stay in the CG, which can cause more pain, ineffective cough and limited mobilization.

In our series, patients who received Progel^TM during surgery had a significantly lower median hospitalization compared to the CG (3 vs. 5 days; P<0.001). These results confirm the findings of other authors (24). Park et al. (23) found a median duration of chest tubes of 2 days and a median LOS of 3 days in patients were Progel^TM was used. Allen and colleagues (22) in their randomized trial showed a significant reduction of the LOS in patients who received Progel^TM intraoperatively compared to patients where Progel^TM was not used (6 vs. 7 days; P=0.028).

Limitations of the study

The limitations of this study must also be considered. First, there might be a selection bias among the groups due to the retrospective assignment of the patients to surgical arms. Secondly, the lack of randomization in this study means that the two groups could differ both on measured and unmeasured factors. Thirdly, there is a lack of standardised protocol to govern the usage of the sealant, so there could be some small differences among the two surgeons on the application of Progel; however, the aim of this study is also to inform us all in this regard. Finally, different surgical approach RATS vs. VATS may be a confounding factor.

Conclusions

In our multicentric study, the use of Progel proved to be safe and useful in reducing the LOD, LOS and the rate of PALs, especially in patients who underwent a complex segmentectomy following a minimally-invasive resection.

Acknowledgments

We would like to thank the European Society of Thoracic Surgeons for letting us present the abstract of this article as a poster at the 31^st edition of the Annual European Conference on General Thoracic Surgery Meeting in Milan, in 2023.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1054/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1054/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1054/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-2025-1054/coif). A.B. reports receiving grants from Intuitive Surgical, Inc. 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 an audit project, approved by the Institutional Ethics Board of Guy’s and St Thomas NHS Foundation Trust (No. 14012). All participating centres were informed and agreed the study. 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/.

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