
==== Front
Intern Med
Intern Med
Internal Medicine
0918-2918
1349-7235
The Japanese Society of Internal Medicine

38220189
10.2169/internalmedicine.3048-23
Original Article
Effectiveness of AERO Stent Placement for Malignant Airway Disorder in Patients with a Poor Performance Status
Takigawa Yuki 1
Sato Ken 1
Kudo Kenichiro 1
Minami Daisuke 12
Shiraha Keisuke 1
Inoue Tomoyoshi 1
Matsuoka Suzuka 1
Fujiwara Miho 1
Mitsumune Sho 1
Watanabe Hiromi 1
Sato Akiko 1
Fujiwara Keiichi 1
Shibayama Takuo 1
1 Department of Respiratory Medicine, NHO Okayama Medical Center, Japan
2 Department of Respiratory Medicine, Hosoya Hospital, Japan
Correspondence to Dr.　Yuki Takigawa, tacky1024@gmail.com

13 1 2024
15 8 2024
63 16 22772282
10 10 2023
27 11 2023
Copyright © 2024 by The Japanese Society of Internal Medicine
https://creativecommons.org/licenses/by-nc-nd/4.0/ The Internal Medicine is an Open Access journal distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Objective

Airway stenting is an established procedure for treating various airway disorders. The AERO stent (Merit Medical Systems, South Jordan, USA) is a fully covered self-expandable metallic stent approved for use in Japan in 2014. However, its effectiveness in treating malignant airway disorders in patients with a poor performance status remains unclear. Therefore, we investigated the safety and efficacy of the AERO stent in patients with malignant airway disorders and a poor performance status.

Methods

We retrospectively reviewed the medical records of all patients who underwent AERO stent placement at our institute between April 2016 and March 2022, and 21 patients underwent 25 procedures for malignant airway disorders. All AERO stenting procedures were performed using an over-the-wire delivery system with flexible and/or rigid bronchoscopy.

Results

Eighteen of the 21 patients (85.7%) had a poor general condition (Eastern Cooperative Oncology Group performance status 3 or 4). AERO stents were successfully placed in 23 of the 25 procedures and migrated in the remaining 2 cases. Complications occurred in 10 cases, with infection being the most common (3 cases). Fourteen patients (66.6%) showed an improvement in their performance status. In addition, 5 of the 6 intubated patients were extubated following AERO stenting, and 11 patients subsequently received anticancer treatment.

Conclusion

The placement of the AERO stent is useful in patients with a poor performance status, including those who are intubated and afflicted with malignant airway disorders.

AERO stent
bronchoscopy
airway disorder
airway intervention
poor performance status
==== Body
pmcIntroduction

Airway stenting is an established procedure for the treatment of various airway disorders, such as stenosis and fistulas. It is considered one of the most important interventional treatments for airway conditions.

Tracheobronchial stents are categorized into self-expandable metal stents (SEMSs), silicone stents, and hybrid SEMSs. The AERO stent, developed by Merit Medical Systems, South Jordan, USA, is a fully covered hybrid SEMS that was approved for use in Japan in 2014. It offers the advantages of both SEMS and silicone stents. Although there have been a limited number of case reports and only a single research article evaluating AERO stent placement in Japan (1-3), previous studies have suggested its utility in treating malignant airway disorders. However, its effectiveness in patients with a poor performance status (PS) remains unclear.

We therefore investigated the effectiveness and safety of the AERO stent in treating patients with malignant airway disorders and a poor PS.

Materials and Methods

Patients and study design

We retrospectively reviewed the medical records of patients who underwent AERO stent placement at the National Hospital Organization of the Okayama Medical Center in Japan between April 2016 and March 2022. The study population included patients with 1) dyspnea and hypoxemia due to airway stenosis and 2) tolerance to general anesthesia or intravenous anesthesia during bronchoscopy and 3) who were referred to our hospital because of the patient's strong willingness to undergo the treatment. Final eligibility was determined by the bronchoscopic intervention team of the Department of Respiratory Medicine.

Written informed consent for the procedure was obtained from all patients before stent placement. This study was approved by the Institutional Review Board of the Okayama Medical Center (approval no.: RINKEN 2021-059; approval date: March 18, 2022) and conducted in accordance with the principles of the Declaration of Helsinki.

Procedures

Stent placement was performed using rigid (EFER BRONCHOSCOPE; Harada Corporation, Osaka, Japan) and flexible (P260F, 1T-260, P-290, or 1TQ-290 bronchoscopes; Olympus, Tokyo, Japan) bronchoscopes. The procedure also involved argon plasma coagulation, an electrocautery snare, an airway balloon, hot biopsy forceps, and a cryoprobe. Although both over-the-wire (OTW) and direct visualization systems are currently available for AERO stent delivery, only the OTW system was used. In the OTW delivery system, the stent is introduced into the stenotic lesion using a guidewire through a rigid bronchoscope or an intubated tube.

Statistical analyses

The overall survival (OS) was calculated from the date of AERO stent placement until death. It was evaluated using the Kaplan-Meier method and compared using the log-rank test. All statistical analyses were performed using the RcmdrPlugin software program with EZR version 1.61 (4).

Results

Patient characteristics

A summary of all of the patients investigated is shown in Table 1. Between April 2016 and March 2022, 25 AERO stent placement procedures were performed in 21 patients for the treatment of airway disorders (Table 2). All patients presented with airway disorders related to malignant diseases. The most common primary site was non-small-cell lung cancer (NSCLC), followed by esophageal cancer. Eighteen of the 21 patients (85.7%) had a poor general condition, with an Eastern Cooperative Oncology Group (ECOG) PS of 3 or 4 at the time of the first procedure. Nineteen patients (90.4%) required supplemental oxygen therapy, of whom 6 (28.5%) required intubation and mechanical ventilation. Intensive-care unit admission was necessary before stenting in 8 cases (47.6%). Eleven patients subsequently received chemotherapy and/or radiotherapy. The stents were placed in various locations, including the trachea [9 procedures (36%)], left main bronchus [9 (36%)], right main bronchus [4 (16%)], and right bronchus intermedius [2 (8%)]. The stent diameter and length are listed in Table 3.

Table 1. Patients who Underwent AERO Stent Placement at the NHO Okayama Medical Center between April 2016 and March 2022.

Case No.	Age	Sex	Cancer	Location	Supplemental oxygen	ECOG PS	Treatment after stenting*	Survival after stenting (months)	Complication	
Before stenting	After stenting	
1	84	M	NSCLC	Trachea	No	2	2	No	2.46	-	
2	76	M	NSCLC (PD-L1 high)	Carina	Yes (intubated)	4	1	ICI	2.00	-	
3	61	M	EC	LMB	Yes (intubated)	4	4	No	1.80	Pneumonia	
4	52	M	SCLC	Trachea	No	4	3	Chemotherapy	2.69	Neck abscess	
5	62	M	NSCLC	Trachea	Yes	4	1	CRT, ICI	13.50	Pneumonia	
6	67	M	NSCLC	RBI	Yes	3	2	Chemotherapy RT, ICI	8.07	-	
7	69	M	EC	Trachea	Yes	2	1	Yes	8.70	-	
8	68	F	TC	Trachea	Yes	3	2	No	2.33	Migration	
9	87	M	TC	Trachea	Yes	4	3	No	2.60	-	
10	67	F	BC	RBI	Yes (intubated)	4	2	Yes	14.8	-	
11	71	F	TC	Trachea	Yes	3	3	No	2.00	Esophagus disorder	
12	70	M	NSCLC	RMB	Yes (intubated)	4	1	Chemotherapy, RT, ICI	9.26	-	
13	72	M	NSCLC	RMB	Yes	4	4	No	1.00	-	
14	71	M	NSCLC (PD-L1 high)	RMB	Yes	4	3	No	1.11	-	
15	74	M	NSCLC (PD-L1 high)	LMB	Yes (intubated)	4	2	Chemotherapy RT	3.31	Esophagus disorder, pneumonia	
16	71	F	NSCLC (PD-L1 high)	LMB	Yes	2	2	Chemotherapy RT	4.13	Atelectasis	
17	67	F	NSCLC	Trachea	Yes	4	2	RT	6.97	Esophagus disorder	
18	63	F	BC	LMB	Yes	3	2	No	4.14	-	
19	52	M	EC	1.LMB 2.Trachea	Yes (intubated)	4	1	Yes	7.10	Migration, granulation tissue formation	
20	65	M	EC	LMB	Yes	4	4	No	0.56	-	
21	84	M	PC	Trachea	Yes	3	3	No	2.46	-	
ECOG PS: Eastern Cooperative Oncology Group performance status, NSCLC: non-small cell lung cancer, EC: esophagus cancer, TC: thyroid cancer, BC: Breast cancer, PC: prostate cancer, LMB: Left main bronchus, RMB: Right Main bronchus, RBI: Right bronchus intermedius, RT: radiation therapy, ICI: immune checkpoint inhibitor

*For lung cancer, detailed treatment was indicated.

Table 2. Summary of Patient Characteristics and Classification.

No. of patients	21	
No. of procedures	25	
Sex (Male / Female)	15 / 6	
Median age (range), years	68 (52-87)	
Primary site		
Lung cancer	11	
Esophagus cancer	4	
Thyroid cancer	3	
Breast cancer	2	
Prostate cancer	1	
No. of patients requiring supplemental oxygen	19	
No. of patients admitted to ICU	8	
No. of intubated patients	6	
ECOG PS at admission		
1	0	
2	3	
3	5	
4	13	
Anticancer treatment after stenting	11	
Stent removal	4	
ECOG PS: Eastern Cooperative Oncology Group performance status, ICU: Intensive care unit

Table 3. Summary of Stent Types and Methods of Procedure.

Stent type: diameter x length (mm)	n=25	
10×30	2	
10×40	4	
12×20	1	
12×40	4	
14×20	1	
14×40	2	
16×40	2	
16×60	3	
18×60	4	
18×80	1	
20×60	1	
Bronchoscope		
Rigid plus flexible bronchoscopy	11	
Flexible bronchoscopy via intubated tube	14	
Anesthesia		
General anesthesia	19	
Intravenous anesthesia	6	
Median procedure time, min (range)	53 (24-125)	

Nineteen procedures were performed in an operating room with patients under general anesthesia, while six procedures were performed using a flexible bronchoscope via intubated tubes in the endoscopy center under intravenous (i.v.) anesthesia with midazolam and fentanyl (Table 3). The median duration of intravenous anesthesia was 41.5 (range, 31-125) min, whereas that of general anesthesia was 54 (range, 24-120) min. I.v. anesthesia was administered using midazolam (median, 7.5 mg; range, 5-11 mg) and fentanyl (median, 0.85 mg; range, 0.06-0.09 mg).

Efficacy

Improvements in the ECOG PS were observed in 14 patients, 10 of whom received subsequent anticancer therapy (Table 1). In particular, the physical condition of 10 of the 13 (77%) patients with an ECOG PS of 4 improved after bronchoscopic intervention. Supplemental oxygen therapy was no longer required after the AERO stenting procedure in 13 patients (Table 4). Five of six intubated patients were successfully extubated after AERO stent placement (Fig. 1). The details of the patient in one case (Case 3) who could not be extubated were as follows: although the airway stenosis was improved by AERO stenting, the pneumonia caused by the tracheoesophageal fistula present before AERO stenting showed no improvement and persisted.

Table 4. Summary of Oxygen Status.

Case No.	Supplemental oxygen (L/minutes)	Oxygenation improvement	
Before stenting	After stenting	
1	0	1		
2	IPPV	0	Yes	
3	IPPV	IPPV		
4	2	2		
5	NPPV	0	Yes	
6	2	0	Yes	
7	2	0	Yes	
8	5	0	Yes	
9	4	0	Yes	
10	IPPV	0	Yes	
11	3	2	Yes	
12	IPPV	0	Yes	
13	0	0		
14	NPPV	2	Yes	
15	IPPV	0	Yes	
16	2	2		
17	5	0	Yes	
18	4	2	Yes	
19	IPPV	0	Yes	
20	5	0	Yes	
21	2	1	Yes	
IPPV: Invasive Positive Pressure Ventilation, NPPV: Non-Invasive Positive Pressure Ventilation

Figure 1. (A) Radiograph obtained before stent placement in a patient with esophageal cancer (case 15). (B) Bronchoscopic image obtained before stenting in case 15. (C) Radiograph obtained after stent placement in case 15. (D) Bronchoscopic image obtained after AERO stent placement in case 15.

The median survival time (MST) of all patients was 2.70 (range, 0.56-14.8) months (Fig. 2A). The median survival time for lung cancer was 3.31 (range, 1.00-13.50) months. Patients who underwent chemotherapy and/or radiotherapy after AERO stent placement demonstrated a longer survival than those receiving best supportive care alone [MST, 6.97 vs. 2.16 months, respectively; p＜0.001 (log-rank test); Fig. 2B]. Thirteen (61%) patients were discharged. The remaining eight patients died in the hospital due to worsening of their condition despite receiving the best supportive care.

Figure 2. (A) Kaplan-Meier plots of all patients who underwent AERO stenting (n=21). The median survival time was 82 (95% confidence interval, 61-128) days. (B) Kaplan-Meier plots of the overall survival of patients who underwent AERO stenting with (a) and without (b) chemotherapy and/or radiation therapy [median, 212 vs. 66 days; p<0.001 (log-rank test)].

Spirometry improvements could not be evaluated because many patients had poor respiratory conditions, and preoperative assessments were not feasible.

Safety

Stent-related complications occurred in nine patients, including esophageal disorders in three cases, migration and recurrent pneumonia in two cases each, and atelectasis, neck abscess, and granulation tissue formation in one case each (Table 1). In patients with neck abscess, percutaneous drainage is necessary in conjunction with the AERO stent. Stent removal was considered; however, the patient's condition deteriorated due to the progression of small-cell lung cancer, preventing stent removal.

Stent removal

Stent removal was successfully performed in 4 patients (19%). Two stents were removed because of airway reopening in response to post-stenting chemoradiotherapy, and two stents were removed due to stent migration. Two other patients who underwent stent removal without migration had NSCLC and survived for 13.5 months in one and 9.26 months in the other. All removal procedures were safely performed using rigid bronchoscopy and did not result in substantial complications.

Discussion

Airway interventions for patients with malignant airway disorders have been reported to prolong the survival, resulting in significant improvements in clinical symptoms (5,6). Although silicone stents are still the first choice for patients with airway disorders in our hospital, the AERO stent has been used 25 times since insurance coverage was initiated.

The advantages of the AERO stent include placement without the need for rigid bronchoscopy, easy stent removal if no longer needed, and a reduced likelihood of unexpected migration (7). However, the usefulness of AERO stents in patients with a poor PS remains unclear. In this study, 14 of the 18 patients with a poor general condition showed an improvement in the ECOG PS after AERO stent placement. In addition, five of the six intubated patients were successfully extubated after stent placement. Patients who were extubated and received additional treatment with rehabilitation showed a longer OS than non-intubated patients. This study suggests that a poor general condition due to airway stenosis can be improved by AERO stenting. Thus, AERO stent placement can allow for additional anti-cancer treatment and improve patients' general condition, even in those with severe airway stenosis.

Two previous studies have reported that patients with a poor ECOG PS have a short survival time after airway stenting (8,9). In contrast, SEMS placement in patients with a poor ECOG PS has been shown to be effective against malignant airway disorders (10). Another study reported improvements in airway intervention results, especially in patients with an ECOG PS 3-4, but did not include the AERO stent. The utility of airway stenting in patients with a poor ECOG PS is thus controversial (11).

The MST of the overall population was shorter than that reported in a previous study on AERO stent placement (3). However, this may be due to the larger number of patients with poor PS in our study than in the previous study. In addition, the survival of patients receiving chemotherapy/radiotherapy after AERO stenting was shorter, possibly due to the same reason. In contrast, patients who did not receive chemotherapy or radiotherapy after AERO stenting died within two months. However, the MST in the intubated patients was over five months in our study. Therefore, subsequent anticancer treatment following AERO stenting may lead to a longer survival. Thus, attempting AERO stenting is worthwhile even in patients who have been intubated, as the improvement in PS after stenting may allow for the performance of further anti-cancer treatments.

Immune checkpoint inhibitors (ICIs) were used after AERO stenting in four NSCLC cases. In addition, two of the four cases were able to undergo stent removal. Although the difference was not significant, the group that received ICIs tended to have a longer survival than patients who did not receive ICIs. The PD-L1 expression in NSCLC patients was as follows: ≥50% in cases 2, 14, 15, and 16; and ＜50% in cases 5, 6, 12, and 17. The remaining cases had no available data concerning the PD-L1 expression.

Furthermore, airway stenting is associated with a higher infection rate (12). Ost et al. reported that the AERO stent is associated with a significantly shorter time to infection than other stents, although silicone stents showed an increased risk of migration (7). However, our cohort showed only two cases of respiratory infection and one case of neck abscess. This may be because our patients were treated with acetylcysteine-nebulized inhalation to increase airway clearance after stent placement (13). Therefore, the incidence of infections related to stent placement was low in this study. Moreover, stent collapse was not observed in this study because of the accuracy of preoperative airway diameter measurement using a SYNAPSE VINCENT (bronchoscopic navigation-dedicated software program; Fujifilm Medical, Tokyo, Japan). In addition, intraoperative airway diameter measurements with an airway balloon were performed, and discussions among the bronchoscopic intervention team took place.

Several limitations associated with the present study warrant mention. First, this was a retrospective study with a small number of cases conducted at a single center specializing in airway stenting. Most of the patients who underwent stent placement were referred to our institution by another hospital for bronchoscopic intervention. Second, AERO stent placement using only a flexible bronchoscope was useful for patients with a poor general condition; however, we had the benefit of using rigid bronchoscopy in cases where unexpected problems occurred during the stent procedure. Rigid bronchoscopy is preferred if debulking is required. As the use of AERO stents in clinical practice continues to increase in Japan, the creation of large clinical datasets will be essential for establishing the efficacy and safety of AERO stents. Third, airway intervention requires expert techniques that have not yet been generalized. Consultation with an expert airway intervention facility is thus necessary for stent placement. However, we wish to make it known that such intervention techniques are available for airway disorders and hope that this article will facilitate the dissemination of this information to internal medicine physicians.

Conclusions

Bronchoscopic intervention using the AERO stent has proven to be effective in patients with a poor PS and malignant airway disorders. A large-scale prospective study may help further demonstrate the usefulness and safety of AERO stenting in such patients.

The authors state that they have no Conflict of Interest (COI).
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