Computed tomography-guided microwave ablation for right middle lobe pulmonary nodules: a retrospective, single-center, case-control study

Abstract

Purpose

This retrospective, single-center, case-control study evaluated the safety and efficacy of Computed tomography (CT)-guided microwave ablation (MWA) for pulmonary nodules located in the right middle lobe (RML), a challenging location associated with a high frequency of complications.

Methods

Between May 2020 and April 2022, 71 patients with 71 RML pulmonary nodules underwent 71 MWA sessions. To comparison, 142 patients with 142 pulmonary nodules in non-RML were selected using propensity score matching. The technical success, technique efficacy, complications, and associated factors were analyzed. The duration of the procedure and post-ablation hospital stay were also recorded.

Results

Technical success was achieved in 100% of all patients. There were no significant differences in technique efficacy rates between the RML and non-RML groups (97.2% vs. 95.1%, p = 0.721). However, both major (47.9% vs. 19.7%, p < 0.001) and minor (26.8% vs. 11.3%, p = 0.004) pneumothorax were more common in the RML group than non-RML group. MWA for RML pulmonary nodules was identified as an independent risk factor for pneumothorax (p < 0.001). The duration of procedures (51.7 min vs. 35.3 min, p < 0.001) and post-ablation hospital stays (4.7 days vs. 2.8 days, p < 0.001) were longer in the RML group than non-RML group.

Conclusions

CT-guided MWA for RML pulmonary nodules showed comparable efficacy compared with other lobes, but posed a higher risk of pneumothorax complications, necessitating longer MWA procedure times and extended hospital stays.

Keywords:

• Right middle lobe
• pulmonary nodule
• microwave ablation
• complication
• pneumothorax

Introduction

Primary lung cancer is the leading cause of cancer-related mortality worldwide [1]. An increasing number of asymptomatic pulmonary nodules, particularly ground-glass nodules (GGNs), have been identified through low-dose computed tomography (CT) screening, typically indicating an early manifestation of lung cancer [2]. Although surgical resection remains the preferred treatment for resectable early-stage lung cancer [3], approximately 30% of patients cannot undergo surgery owing to medical comorbidities, especially inadequate cardiopulmonary function [4]. Percutaneous image-guided thermal ablation (IGTA) serves as a precise and minimally super-invasive treatment option for thoracic tumors, sparing lung parenchyma. It is increasingly accepted as a safe and effective local therapy alternative to surgical resection and radiation therapy [5,6]. These thermal ablation techniques offer several advantages over surgery, including shorter recovery time, reduced bleeding, lower infection rates, and fewer major complications [7]. Radiofrequency ablation, microwave ablation (MWA), cryoablation, and laser ablation are the primary IGTA techniques, with MWA having several advantages over the other methods, including higher energy, shorter ablation time, and reduced susceptibility to the heat sink effect [8]. Furthermore, multiple studies have shown the effectiveness and safety of MWA for early-stage primary lung cancer treatment [9, 10].

Previous studies have emphasized the close association between tumor location and the risk of major complications or inadequate local therapeutic efficacy [11–13]. The right middle lobe (RML), located between the horizontal and oblique fissures and adjacent to the pericardium, is the smallest of all lung lobes [12,14]. In many cases, the MWA antenna traversing the horizontal fissure of the lung implies a heightened risk of complications, such as pneumothorax [11]. The occurrence of pneumothorax causes rapid lung tissue contraction, making it challenging to identify the exact region or resulting in antenna displacement from the tumor, potentially leading to incomplete ablation or even off-target outcomes [15,16]. Until now, no studies have addressed issues related to MWA treatment for pulmonary nodules in this unique location. Consequently, this retrospective, single-center, case-control study was conducted to analyze the safety and efficacy of CT-guided MWA for pulmonary nodules located in the right middle lobe (RML), a challenging location associated with a high frequency of complications.

Materials and methods

Patient cohort and inclusion criteria

This retrospective study was performed in accordance with the principles stated in the Declaration of Helsinki and received approval from the Institutional Review Board of The First Affiliated Hospital of Shandong First Medical University. The approved protocol number is YXLL-KY-2023-S471. All patients provided written informed consent for CT-guided MWA or CT-guided MWA synchronous percutaneous biopsy. Treatment decisions for all patients were made collectively by a multidisciplinary tumor board (including thoracic surgery, radiotherapy, medical oncology, interventional radiology, and radiology). Between May 2020 and April 2022, 1485 consecutive patients were treated through CT-guided percutaneous MWA or synchronous MWA and biopsy (Figure 1). In total, 71 out of 1485 patients with RML pulmonary nodules were included. Based on our institutional database, 142 out of 1485 patients with non-RML pulmonary nodules were selected, using nearest neighbor propensity score matching (performed using the R package “MatchIt”) with age, sex, nodule size, type (GGNs or solid nodules), number, and synchronous lung biopsy as matching variables. The baseline characteristics of the two groups are shown in Table 1.

Figure 1. Flowchart illustrating patient selection criteria.

Table 1. Baseline characteristics of patients and pulmonary nodules compared between the RML and non-RML groups.

Characteristics	RML group	Non-RML group	p value
Number of patients	71	142
Number of sessions	71	142
Age (years), mean ± SD	60.2 ± 11.8	61.8 ± 10.9	0.318^a
Age (years), n (%)			0.379
<65	43 (60.6)	77 (54.2)
≥65	28 (39.4)	65 (45.8)
Sex, n (%)			0.099
Male	40 (56.3)	63 (44.4)
Female	31 (43.7)	79 (55.6)
Nodule size (mm), mean ± SD	12 ± 0.6	13 ± 0.6	0.125^a
Nodule size, n (%)			0.415
≤10 mm	36 (50.7)	63 (44.4)
>10, ≤20 mm	28 (39.4)	56 (39.4)
>20, ≤30 mm	7 (9.9)	23 (16.2)
Nodule density, n (%)			0.684
Pure GGN	33 (46.5)	71 (50)
Mixed GGN	16 (22.5)	35 (24.6)
Solid nodules	22 (31.0)	36 (25.4)
Synchronous biopsy, n (%)			1.000
Yes	39 (54.9)	78 (54.9)
No	32 (45.1)	64 (45.1)
Pathology, n (%)			0.847^b
No#	26 (36.6)	60 (42.3)
AIS	16 (22.5)	25 (17.6)
MIA	9 (12.7)	19 (13.4)
IA	17 (23.9)	34 (23.9)
SCC	3 (4.2)	4 (2.8)
Distance to RML edge, n (%)			0.759
≤10 mm	46 (64.8)	95 (66.9)
>10 mm	25 (35.2)	47 (33.1)
Penetration of interlobar fissure, n (%)			<0.001
Yes	16 (22.5)	7 (4.9)
No	55 (77.5)	135 (95.1)
Lesion displacement, n (%)			<0.001
Yes	15 (21.1)	7 (4.9)
No	56 (78.9)	135 (95.1)

RML: right middle lobe; GGN: ground-glass nodule; AIS: adenocarcinoma in situ; IA: invasive adenocarcinoma; MIA:minimally invasive adenocarcinoma; SCC: squamous cell carcinoma.

^aTwo independent samples t-test.

^bFisher’s exact test.

^cNo, patients with high-risk GGNs that persisted for a minimum of six months during follow-up but lacked histological confirmation.

The inclusion criteria included individuals who (1) aged 18–75 years, with an Eastern Cooperative Oncology Group Performance Status of 0–2; (2) solitary pulmonary nodules with a maximum diameter of 8–30 mm, located in the peripheral lung; (3) not suitable for radical surgery owing to pathologically confirmed primary lung cancer; (4) pure GGNs or mixed GGNs without histological diagnoses, but persisted for >6 months, exhibited consolidation tumor ratios ≤50%, increased in size or density, and showed highly suspicious malignancy on CT images; (5) no history of chest surgery; and (6) adequate cardiopulmonary, lung, hepatic, and renal functions. The exclusion criteria covered those individuals with (1) solitary pulmonary nodules without histological confirmation, (2) pathologically verified benign lesion, (3) multiple pulmonary nodules, (4) loss to follow-up, and (5) solitary lesions smaller than 8 mm or larger than 30 mm.

Procedures

The MTC-3C MWA system (Vison-China Medical Devices R&D Center) or ECO-100A1 MWA system (ECO Medical Instrument) were used as microwave generators. They were operated at a frequency of 2450 ± 50 MHz, with the primary output power set at 30 or 40 W. The microwave antenna had an outside diameter of 16–19 G and an effective length of 150 or 180 mm, featuring a 1.5 cm radiating tip. The antenna surfaces were kept cool via a water circulation cooling system. Detailed MWA procedures were documented in our previous studies [17–19]. After the procedure, CT scans were obtained immediately to identify any complications to deal with.

Follow-up

A CT scan was performed 24 h after MWA to identify MWA-related complications. Subsequently, patients underwent follow-up contrast-enhanced CT scans at 1-month post-ablation, at 3-month intervals during the first year, 6-month intervals for the next two years, and then annually. The last follow-up date was 23 September 2023. The follow-up CT images were evaluated by two radiologists with at least 10 years of experience.

Outcome criteria

The response to MWA, including technical success and technique efficacy, was determined using follow-up contrast-enhanced CT scans. Technical success indicated the procedure’s compliance with the established protocol. Technique efficacy was used to assess the MWA response, mainly signifying the attainment of complete ablation. The primary technique efficacy rate indicated the proportion of patients who achieved complete ablation at three months post-procedure during the follow-up period. Complete ablation could manifest as any of the following: (1) lesion disappearance; (2) complete cavity formation; (3) fibrosis or scarring (the most common); (4) solid nodule involution or no change, with no contrast‑enhanced signs on CT and/or no FDG uptake on PET/CT; and (5) atelectasis, referring to lesions in atelectasis with no contrast-enhanced signs on CT and/or no FDG uptake on PET/CT [20,21].

Complications

Treatment-related complications were defined as symptoms occurring within 30 days of the procedure and were assessed based on the Society of Interventional Radiology (SIR) criteria [22]. Minor complications were categorized as SIR A and SIR B, whereas major complications were classified as SIR C and SIR D. SIR E denoted death.

Statistical analysis

R (version 3.5.2; R Foundation for Statistical Computing) and the R package “MatchIt” (1:2 matching with the nearest neighbor) were employed to conduct propensity matching to select patients for the control group. Statistical analyses were performed using SPSS 24.0 (SPSS Inc., Chicago, IL). Numerical variables were presented as means and standard deviations, whereas categorical variables were expressed as percentages. Comparisons of numerical variables between the RML and non-RML groups were performed using independent t-tests or Mann–Whitney U tests, contingent on distribution characteristics. The association of categorical variables between the two groups was analyzed using Pearson’s χ2 test or Fisher’s exact test. A univariate conditional logistic regression model was applied to explore factors influencing pneumothorax. Factors with a P-value of <0.05 were designated as alternative variables, and multivariate analysis was employed to determine whether a factor was an independent predictor of pneumothorax. A two-sided P-value of <0.05 was considered statistically significant.

Results

Patients and nodule characteristics

In total, 71 patients (40 men and 31 women) with 71 RML pulmonary nodules underwent 71 MWA sessions, with 40 sessions involving synchronous CT-guided percutaneous MWA and biopsies. The patients’ mean age was 60.2 ± 11.8 years. The mean size of the 71 nodules was 12 ± 6 mm. Among them, 46 nodules were located within 10 mm of the RML border, with a median distance of 5 mm (range: 1–10 mm). The remaining 25 nodules were more than 10 mm from the RML edge, with a median distance of 20 mm (range: 11–39 mm). Table 1 shows the patients’ baseline characteristics.

During the procedures, the RML group experienced a higher incidence of antenna penetration through the interlobar fissure (22.5% vs. 4.9%, p < 0.001) and lesion displacement (21.1% vs. 4.9%, p < 0.001) compared with the non-RML group.

Outcome

All nodules in both groups exhibited complete coverage by ground-glass opacity, extending 5–10 mm beyond the legion at 24–48 h post-procedure, indicating the achievement of technical success in all patients. At the three-month post-procedure 2 of 71 lesions in the RML group and 7 of 142 lesions in the non-RML group displayed incomplete ablation. No significant differences were found between the two groups regarding the primary technique efficacy rate (97.2% vs. 95.1%, p = 0.721). All incompletely ablated nodules underwent repeated ablation 1–2 months after the initial procedure.

Until 23 September 2023, the median follow-up duration was 23.9 months (range: 13.6–39.3 months) in the RML group and 23.8 months (range: 12.1–39.8 months) in the non-RML group. No cancer‑related deaths or local progression occurred in either group.

Complications

No periprocedural deaths occurred in either group, and MWA was well-tolerated by both. Details of periprocedural complications are outlined in Table 2. Notably, bronchopleural fistula, pericardial effusion, and air embolism were absent in both groups. The mean procedure time (51.7 min vs. 35.3 min, p < 0.001) and post-ablation hospital stays (4.7 days vs. 2.8 days, p < 0.001) were longer in the RML group compared with the non-RML group (Table 2).

Table 2. Complications and post-ablation hospital stay compared between the RML and non-RML groups.

Complications	RML group	Non-RML group	p value
Major complications, n (%)
Pneumothorax	34 (47.9)	28 (19.7)	<0.001
Pleural effusion	3 (4.2)	7 (4.9)	1.000^b
Hemorrhage	2 (2.8)	3 (2.1)	1.000^b
Infection	3 (4.2)	2 (1.4)	0.336^b
Minor complications, n (%)
Pneumothorax	19 (26.8)	16 (11.3)	0.004
Pleural effusion	21 (29.6)	31 (21.8)	0.215
Hemorrhage	3 (4.2)	7 (4.9)	1.000^b
Chest pain	5 (7.0)	6 (4.2)	0.512^b
Procedure time (min), mean ± SD	51.7 ± 17.6	35.3 ± 11.7	<0.001
Hospital stays (day), mean ± SD	4.7 ± 2.2	2.8 ± 1.4	<0.001

RML, right middle lobe.

^bFisher’s exact test.

In further analysis, we employed unconditional logistic regression models to identify potential influencing factors. In univariate analysis, antenna penetration through the interlobar fissure (p = 0.018), lesion displacement (p = 0.029), and RML nodule location (p < 0.001) were significantly associated with pneumothorax occurrence. In multivariate analysis, MWA treatment for RML pulmonary nodules was established as an independent risk factor for pneumothorax (Table 3). Three typical cases illustrating the risk factors for pneumothorax in RML pulmonary nodules treated with MWA are presented in Figures 2–4.

Figure 2. A female, 55-year-old patient with GGN-like lung cancer in the RML underwent MWA. (A) A mixed GGN located in the RML with a diameter of 12 mm. (B) An antenna was inserted into the tumor. (C) The lesion was covered by ground-glass opacity, and a small amount of pneumothorax was observed immediately post-ablation. (D) The lesion involuted at 1-month post-ablation. (E) The lesion gradually involuted at 12-months post-ablation. (F) The lesion involuted into a band at 36-months post-ablation.

Figure 3. A male, 49-year-old patient with GGN-like lung cancer in the RML underwent MWA. (A) A mixed GGN located in the RML with a diameter of 11 mm. (B) An antenna was inserted into the tumor. (C) A small amount of pneumothorax occurred immediately after MWA. (D) The lesion was covered by ground-glass opacity, displaying a “fried egg” sign, and the pneumothorax volume did not increase. (E) The lesion gradually involuted at 6-months post-ablation. (F) The lesion involuted into a fibrous cord at 14-months post-ablation.

Figure 4. A female, 65-year-old patient with GGN-like lung cancer in the RML underwent MWA. (A) A mixed GGN located in the RML with a diameter of 17 mm. (B) An antenna was inserted into the tumor through the interlobar fissure. A large amount of pneumothorax occurred during the procedure, causing tumor displacement. (C) Continuous negative-pressure chest drainage was performed. (D) After negative-pressure aspiration, the procedure was continued. (E) The lesion was covered by ground-glass opacity, displaying a “fried egg” sign, and the amount of pneumothorax and subcutaneous emphysema did not increase at 72 h after MWA. (F) The lesion gradually involuted at 1 month after MWA. (G) The lesion gradually involuted at 10 months after MWA. (H) The lesion gradually involuted into a fibrous scar at 25 months after MWA.

Table 3. Univariate and multivariate conditional logistic regression analysis of risk factors for pneumothorax.

Variables	Univariate analysis		Multivariate analysis
	OR (95% CI)	p	OR (95% CI)	p
Age (≥65 vs. <65)	1.430 (0.829, 2.467)	0.198
Sex (male vs. female)	1.473 (0.857, 2.532)	0.161
Nodule size
>10, ≤20 mm vs. ≤10 mm	1.068 (0.594, 1.921)	0.825
>20, ≤30 mm vs. ≤10 mm	2.036 (0.886, 4.678)	0.094
Nodule density
(mixed GGN vs. pure GGN)	0.656 (0.326, 1.320)	0.237
(Solid nodule vs. pure GGN)	0.925 (0.483, 1.774)	0.816
Synchronous lung biopsy (yes vs. no)	0.611 (0.352, 1.062)	0.081
Pathology
AIS vs. No^a	1.028 (0.479, 2.205)	0.944
MIA vs. No^a	1.039 (0.434, 2.491)	0.931
IA vs. No^a	1.218 (0.602, 2.464)	0.582
SCC vs. No^a	2.141 (0.451, 10.178)	0.338
Distance to RML edge (>10 mm vs. ≤10 mm)	1.108 (0.627, 1.958)	0.725
Penetration of interlobar fissure (yes vs. no)	3.076 (1.209, 7.824)	0.018	1.669 (0.590, 4.723)	0.334
Lesion displacement (yes vs. no)	2.848 (1.111, 7.305)	0.029	1.577 (0.551, 4.514)	0.396
Procedure time	1.013 (0.996, 1.030)	0.148
Nodule location (RML vs. Non-RML)	6.558 (3.450, 12.464)	<0.001	5.705 (2.921, 11.144)	<0.001

RML: right middle lobe; GGN: ground-glass nodule; AIS: adenocarcinoma in situ; IA: invasive adenocarcinoma; MIA: minimally invasive adenocarcinoma; SCC: squamous cell carcinoma.

^aNo, patients with high-risk GGNs that persisted for a minimum of six months during follow-up but lacked histological confirmation.

Discussion

In this retrospective study, a propensity score–matched non-RML cohort was used to assess the safety and efficacy of MWA for pulmonary nodules located in the RML. The study included 71 and 142 MWA sessions in the RML group and non-RML group (as the control), respectively. The study revealed a 100% technical success rate in all patients. The technique efficacy rate was 97.2% and 95.1% (p = 0.721) in the RML group and non-RML group, respectively, suggesting that MWA for RML pulmonary nodules is as effective as in non-RML. Others studies investigating MWA for special locations reported similar findings [23–25]. For instance, in a study involving 66 lung tumors adjacent to interlobar fissures, a complete ablation rate of 95.5% was observed [23]. Wang et al. [24] evaluated MWA treatment for lung tumors adjacent to the mediastinum and reported a technical success rate of 97.96%, with 16.33% (16 out of 98) of tumors showing local progression during a median follow-up duration of 9.2 months (range: 3.5–16.5 months). Our improved technique efficacy may be attributed to the inclusion of a large proportion of GGNs and pulmonary nodules smaller than 30 mm, ensuring the maintenance of a safety margin of at least 5 mm on either side of the lesion, which is vital for technique efficacy in MWA [8,26,27]. Additionally, the use of immediate and 1–3-months post-ablation contrast-enhanced CT fusion with the planning CT allows for rapid and reliable assessment of the MWA results, with the option for repeated MWA.

Pneumothorax was the most frequent complication in MWA, with reported rates ranging from 21.1% to 63%, necessitating chest drainage in 11.9%–20.9% of cases [16,20,28]. Our study revealed that 74.7% of patients occurred ablation-related pneumothorax, with 47.9% experiencing major complications that required chest drainage, significantly higher than in the non-RML group (19.7%, p < 0.001). There was no significant difference of other major complications included massive pleural effusion (4.2% vs 4.9%, p = 1.000), hemorrhage (2.8% vs 2.1%, p = 1.000) and infection (4.2% vs 1.4%, p = 0.336) between the RML and non-RML groups. Previous studies have reported other complications, mainly pleural effusion, occurred in 2.9–21.7% of patients [29]. In the present study, small to moderate pleural effusion developed in 29.6% and 21.8% of two groups (p = 0.215), respectively. Therefore, pneumothorax is the most complication of MWA for RML pulmonary nodules.

Several factors were considered to increase the risk of pneumothorax, including nodule location, puncture path, antenna size, puncture of a fissure, and other technical factors [30]. A retrospective analysis of 289 CT-guided lung biopsies by Hailemariam et al. [31] demonstrated that pneumothorax most commonly occurred in biopsies of middle lobe lesions (64.7%) compared with lower or upper lobe lesions (26.5% and 31.4%, respectively). RML is located between the horizontal and oblique fissures and puncturing the antenna though the interlobar fissure may be a potential risk factor for pneumothorax in MWA treatment of pulmonary nodules [23]. Moreover, sometimes puncture of a fissure was manipulated to bypass the pulmonary vessels or intertubercular vessels of GGNs to avoid a relatively high risk of hemorrhage. Our study employed univariate and multivariate analyses to compare the incidence of pneumothorax incidence between the two studied groups, with the former analysis showing that puncture of a fissure, lesion displacement, and nodule location in the RML significantly influenced the occurrence of pneumothorax. Multivariate analysis ultimately established nodule location in the RML as an independent risk factor for MWA-related pneumothorax. These results suggest a strong statistically association between pneumothorax and nodule location, potentially explaining the high pneumothorax rate in middle lobe MWA. Therefore, it is imperative to carefully identify fissures around lesions and avoid puncturing them to prevent major pneumothorax. Combining this with other manipulations, such as lesion displacement resulting in repeated antenna adjustments, may further increase the occurrence of pneumothorax.

The mean time of procedure (51.7 min vs. 35.3 min) and post-procedure hospital stay (4.7 days vs. 2.8 days) were significantly longer in the RML group compared with the non-RML group, which aligns with the higher risk of complications, particularly pneumothorax, observed in the RML group. The occurrence of pneumothorax leads to lung tissue shrinkage, making it challenging to target the exact region, sometimes necessitating antenna readjustments and prolonging the MWA procedure. Furthermore, patients with massive pneumothorax may require continuous negative-pressure chest drainage, extending the hospital stay.

This study has several limitations. First, it was a retrospective, single-center, potentially introducing patient selection bias. Second, 36.6% and 42.3% of patients in both groups did not have histological diagnoses. Third, the rate of complications was not compared with the thoracoscopic surgery or other IGTA techniques such as radiofrequency ablation and cryoablation. Therefore, a prospective, multicenter, randomized, controlled study is necessary to evaluate the safety and efficacy of MWA for pulmonary nodules peculiarity located in the RML.

In conclusion, CT-guided MWA for RML pulmonary nodules was shown to have equivalent efficacy to MWA in non-RML, but the incidence of pneumothorax was high, leading to longer MWA procedures and extended hospital stays.

Authors’ contributions

Yanting Hu, Guoliang Xue and Xinyu Liang contributed equally to this article. Yanting Hu and Guoliang Xue were responsible for acquiring the data and drafting the manuscript. Yanting Hu, Guoliang Xue and Xinyu Liang were responsible for the analysis of the data. Zhichao Li, Nan Wang, Pikun Cao, Gang Wang, Haitao Zhang, Wenhua Zhao, Cuiping Han provided and collected the clinical data. Zhigang Wei and Xin Ye were responsible for designing the experiments and supervising the study. All the listed authors have made a substantial, direct, and intellectual contribution to the work and have approved it for publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, Xin Ye. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Additional information

Funding

This study was supported by China Postdoctoral Science Foundation [2023M742168].