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ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 7  |  Page : 2001-2005

Phrenic nerve injury after the percutaneous microwave ablation of lung tumors: A single-center analysis


Departments of Interventional Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China

Date of Submission16-Jun-2020
Date of Decision07-Aug-2022
Date of Acceptance30-Aug-2022
Date of Web Publication11-Jan-2023

Correspondence Address:
Zhengyu Lin
Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_1254_22

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 > Abstract 


Objective: This study aimed to analyze the cases of phrenic nerve injury caused by the percutaneous microwave ablation of lung tumors conducted at our center and to explore the risk factors.
Materials and Methods: The data of 455 patients who underwent the percutaneous microwave ablation of lung tumors at the Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University from July 2017 to October 2021, were retrospectively analyzed. The cases of phrenic nerve injury after the percutaneous ablation were reported to analyze the risk factors involved, such as the shortest distance between tumor margin and phrenic nerve, tumor size, and ablation energy. The groups were divided based on the shortest distance between the tumor edge and the phrenic nerve into group 1, d ≤ l cm; group 2, 1 < d ≤2 cm; and group 3, d >2 cm. Lesions with a distance ≤2 cm were compared in terms of tumor size and ablation energy.
Results: Among the 455 patients included in this study, 348 had primary lung cancer, and 107 had oligometastatic cancer. A total of 579 lesions were detected, with maximum diameter of 1.27 ± 0.55 cm, and the ablation energy was 9,000 (4,800–72,000) J. Six patients developed phrenic nerve injury, with an incidence of 1.32%. For these six patients, the shortest distance from the lesion edge to the phrenic nerve was 0.75 ± 0.48 cm, and the ablation energy was 10,500 (8,400–34,650) J. There were statistically significant differences in phrenic nerve injury among groups 1, 2, and 3 (P < 0.05). In patients with a distance (d) ≤ 2 cm, there were no significant differences in tumor diameter and energy between the phrenic nerve injury group and the non-injury group (P = 0.80; P = 0.41). In five out of six patients, the diaphragm level completely recovered to the pre-procedure state, and the recovery time of the phrenic nerve was 9.60 ± 5.60 months. Another one was re-examined 11 months after the procedure, and the level of the diaphragm on the affected side had partially recovered.
Conclusions: Phrenic nerve injury is a rare but not negligible complication of thermal ablation and is more likely to occur in lesions with a distance ≤2 cm from the phrenic nerve.

Keywords: Microwave ablation, phrenic nerve injury, primary lung cancer, pulmonary metastatic carcinoma


How to cite this article:
Zhong J, Chen J, Lin R, Yan Y, Lin Q, Chen J, Lin Z. Phrenic nerve injury after the percutaneous microwave ablation of lung tumors: A single-center analysis. J Can Res Ther 2022;18:2001-5

How to cite this URL:
Zhong J, Chen J, Lin R, Yan Y, Lin Q, Chen J, Lin Z. Phrenic nerve injury after the percutaneous microwave ablation of lung tumors: A single-center analysis. J Can Res Ther [serial online] 2022 [cited 2023 Jan 27];18:2001-5. Available from: https://www.cancerjournal.net/text.asp?2022/18/7/2001/367458




 > Introduction Top


Microwave ablation is a technique in which polar molecules, such as water molecules and proteins, in tumor tissues vibrate at extremely high speed under the action of a microwave electromagnetic field and produce collisions and friction between molecules at high temperatures (60–150°C) in a short period of time, resulting in cell coagulation necrosis.[1] Microwave ablation has been widely used in the treatment of unresectable early lung cancer and oligometastatic lung carcinoma due to the advantages of being a minimally invasive, precise, and effective treatment.[2],[3] Although the percutaneous microwave ablation of lung tumors has significant advantages, its complications cannot be ignored. The most common one is pneumothorax, followed by hemoptysis, infection, bronchopleural fistula, and chest wall tissue thermal damage, among others.[4] Phrenic nerve injury caused by the pulmonary microwave ablation is rare, and clinicians are not fully aware of it. Thornton et al.[5] found that, in cases of nerve injury after thermal ablation, patients with poor pulmonary basic function showed symptoms such as chest tightness, shortness of breath, and decreased oxygen saturation. Diaphragm palsy caused by phrenic nerve injury can lead to severe physiological consequences, including hypoxemia, hypercapnia, and a 20% reduction in ipsilateral lung oxygen uptake.[6] This study aimed to analyze the cases of phrenic nerve injury caused by the percutaneous microwave ablation of lung tumors conducted at our center and to explore the risk factors.


 > Materials and Methods Top


Materials

Subject

The Ethics Committee of the First Affiliated Hospital of Fujian Medical University approved this study, and all the patients provided the written informed consent. The retrospective analysis was performed on patients who underwent the percutaneous microwave ablation of lung tumors between July 2017 and October 2021. An informed consent was signed prior to the procedure. The procedure was performed under CT guidance, and immediately after it, the ablation range was evaluated through CT scanning. Chest film was checked 1 day after the procedure, and thorax CT scanning was reviewed after 3 days, 1 month, 4 months, and every 6 months thereafter. Based on inclusion and exclusion criteria, 455 patients were enrolled.

The inclusion criteria were as follows: (1) Patients ≥18 years old with lung tumors, who were not eligible for surgery, or refused surgery, and underwent microwave ablation. (2) Primary early non-small cell lung cancer or lung oligometastatic carcinoma diagnosed by pre-procedure pathological examination or MDT discussion. (3) An ECOG score between 0 and 2. (4) The number of tumors ablated by a single operation was ≤3.

And the exclusion criteria included: (1) Patients with failed follow-up or incomplete data. (2) Patients undergoing phrenic nerve protection strategies during the procedure. The general situation of the patients is shown in [Table 1].
Table 1: General information on the patients included in this study

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Methods

Ablation devices and instruments

The microwave ablation equipment comprised a microwave therapy instrument (MTI-5DT, 0-120W, 2450MHZ, Nanjing Great Wall Medical Equipment Co., Ltd.) and a microwave antenna (XR-A1818W, 1.8 mm, 180 mm, Nanjing Great Wall Medical Equipment Co., Ltd.). After puncturing the target lesion, the cold circulation was switched on. Based on the characteristics of the tumor, an appropriate power of 40–60 W was selected, and the duration of the treatment was 2.5–9 min.

Data analysis

To assess the minimum distance between the tumor and the phrenic nerve, the minimum distance between the tumor edge and the nerve (d) was measured.

To evaluate the phrenic nerve injury, the post-procedure chest radiograph or thorax CT was compared with the pre-procedure one, and the relative positions of the affected diaphragm and contralateral muscle were measured before and after the procedure. If the level of the former was significantly higher than that of the latter, the phrenic nerve injury was assumed to have developed. Substantial elevation was defined as elevation with a height greater than the width of an intercostal space.

The groups were divided based on the shortest distance between the tumor edge and the phrenic nerve into group 1, d ≤l cm; group 2, 1 < d ≤2 cm; and group 3, d >2 cm. Lesions with a distance ≤2 cm were compared in terms of tumor size and ablation energy.

Statistical method

The data were statistically analyzed in SPSS version 20.0. For the comparison of measurement data, the normal data were described using the mean and standard deviation. The skewness data were described by the median (range) and were compared using the Mann–Whitney U test. The count data were compared through the X2 test or Fisher's exact probability method. P < 0.05 was considered as statistically significant.


 > Results Top


This study included 455 patients: 579 lesions with a maximum diameter of 1.27 ± 0.55 cm were present and the ablative energy was 9,000 (4,800–72,000) J. Imaging evaluation found that six patients showed significant elevation of the affected diaphragm side on the first day after the procedure, with an incidence of 1.32%. For these six patients, the shortest distance from the lesion edge to the phrenic nerve was 0.75 ± 0.48 cm, including one case of metastatic cancer and five cases of primary lung cancer. The characteristics of patients with phrenic nerve injury are shown in [Table 2]. In group 1, the number of cases with phrenic nerve injury/the number of tumors was 4/11; in group 2, it was 2/20; and in group 3, it was 0/548. The differences among the three groups were statistically significant, as were those between group 3 and the other two groups (P < 0.05) [Table 3]. In patients with d ≤2 cm, the tumor diameter of the phrenic nerve injury group was about 0.90 (0.80–2.30) cm and the energy was 10,500 (8,400–34,650) J, indicating the absence of a significant difference compared with the non-injury group (P = 0.80; P = 0.41), as shown in [Table 4]. Among the six patients, the level of the diaphragm was completely restored to the pre-procedure state in five cases, and the recovery time of the phrenic nerve was 9.60 ± 5.60 months. In the other case, the level of the lateral diaphragm was partially recovered 11 months after the procedure. Imaging data of the ablation and follow-up of patients with phrenic nerve injury are shown in [Figure 1].
Table 2: The characteristics of patients with phrenic nerve injury

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Table 3: Relationship between lesion-phrenic nerve distance and nerve injury

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Table 4: Comparative analysis of the injury and non-injury groups in cases where d ≤2 cm

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Figure 1: Thorax CT scans of a 55-year-old female patient with pulmonary GGO, pathologically indicated invasive adenocarcinoma, with a lesion of 0.8 cm × 0.6 cm. A: the lesion was located in the anterior segment of the upper lobe of the left lung beside the mediastinum, about 0.2 cm away from the phrenic nerve in thorax CT image. B: CT-guided microwave ablation for lung tumor. The microwave antenna was located between the lesion and the aortic arch using a power of 40 W and the ablation time was 5 min. C: pre-procedure CT positioning images showing a normal bilateral diaphragm height. D: anteroposterior chest radiograph 1 day after the procedure showing that the left diaphragm was significantly elevated compared with the contralateral muscle. E: CT localization 1 month after the procedure showing elevation of the left diaphragm. F:CT positioning image 3 months after the procedure showing that the level of the left diaphragm was still elevated. G: CT image 11 months after the procedure showing that the left diaphragm had basically returned to a normal state

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 > Discussion Top


Biopsy is an important approach to identify the property and determine the treatment method of ground-glass nodule (GGN).[7] Not every lesion in this study was supported by pathological evidence. The analysis results of the relationship between imaging features and pathological features of JCOG0201 study suggest that imaging can accurately predict noninvasive lung cancer.[8] Due to this high specificity, GGN with tumor diameter ≤2 cm and consolidation tumor ratio (CTR) ≤0.25 in the JOCG0804 study was not biopsied before enrollment.[9] Patients with malignant tumor history combined dynamic follow-up examination of imaging could be diagnosed metastatic cancer.

Matsui et al.[10] believed that the distance between the phrenic nerve and tumors less than 1 cm is a significant independent risk factor for nerve injury. The results of our study showed that the incidence of phrenic nerve injury was highest in group 1, which is consistent with the findings reported in the above-mentioned study. However, no statistical significance was detected in the phrenic nerve injury differences between groups 1 and 2, which might be related to the small number of cases included. In this study, all phrenic nerve injuries occurred in patients with d ≤2 cm. Therefore, although the power and time of ablation are different for different lesions, it is relatively safe to ablate lesions with a distance of more than 2 cm from the phrenic nerve. It is worth noting that the distance between the lesion edge and phrenic nerve may be shorten during the puncture process, increasing the potential risk of phrenic nerve injury, which needs to be carefully considered during the procedure.

The choice of ablation power and time will produce different ablation results. Gao et al.[11] found that, in the in vitro model of a pig lung, the maximum temperature increased from 75.6 to 106.7°C as the ablation power simultaneously increased by 30–50 W, and the area of tissue necrosis significantly increased. Therefore, a higher ablation energy augments the risk of phrenic nerve injury. Sebek et al.[12] showed that the ablation boundary of a 1-cm tumor could exceed 5 mm when the power and time were set at 30 W and 6 min, respectively. In this study, the median energy value of the phrenic nerve injury group was 10,500 J, which was similar to the above-mentioned study. Large tumors often require multiple ablations or the use of higher levels of energy to be completely inactivated, potentially increasing the risk of neurological damage. In this study, the average diameter of tumors was only 1.27 cm, and the energy required for ablation was small. More data may be needed to further verify the relationship between energy and phrenic nerve injury.

Prevention is the key to avoid phrenic nerve injury. In particular, it is essential to be familiar with the anatomy of the phrenic nerve and to be able to judge the relationship and distance between it and the lesion. The running of the phrenic nerve is usually not seen on CT tomography, but many studies have reported its imaging anatomy.[13],[14] The phrenic nerve starts from the cervical plexus C3–C5; enters the thoracic cavity between the subclavian artery and vein; passes in front of the lung root, between the mediastinum pleura and the pericardium; and descends toward the diaphragm. The left phrenic nerve passes through the muscle, while the right one passes through the central tendon or vena cava foramen to reach the diaphragm, which is controlled by motor fibers. Sensory fibers are distributed to the pleura, pericardium, part of the peritoneum, the right phrenic nerve and serous membrane branching to the liver, gallbladder, and extrahepatic biliary tract.

Selecting the appropriate puncture path can help to avoid phrenic nerve injury. For lesions located near the nerve, with potential risk of injury, the appropriate puncture path should be selected, and the area to be ablated should exclude the phrenic nerve. Artificial pneumothorax has been proved to be an effective way to prevent nerve injury.[15] It can be used to achieve the separation of the lesion and the mediastinal pleura with the injection of only a small amount of gas combined the adjustment of the complex position. Lin et al.[16] applied this method to mediastinal puncture biopsy. Artificial pleural effusion is an effective measure to prevent nerve injury. In abdominal viscera ablation, many research studies have used artificial ascites to protect adjacent structures, such as the gastrointestinal tract and diaphragm.[17],[18],[19] When ultrasound guides liver ablation, artificial pleural effusion can be used to overcome the poor visual field, eliminate the influence of gas, and ablate diaphragmatic apex lesions.[20] Artificial pleural effusion can also be used for lung ablation.

In this study, the diaphragm height of the patients with phrenic nerve injury was recovered or partially recovered, suggesting that the nerve had also been repaired to varying degrees. Morisaki et al.[21] showed that glucocorticoids could improve not only the symptoms of peripheral nerve injury but also the rate of myelin sheath formation. It was suggested that, if phrenic nerve injury can be found in time after the procedure, patients may benefit more if the duration of glucocorticoid use is extended from 3 days to 1 week. In addition, mecobalamin, vitamin B12, nerve growth factor, and other drugs can effectively promote the repair and induction of nerve cells, and patients with phrenic nerve injury can benefit from them.[22]

In conclusion, phrenic nerve injury is a rare but not negligible complication of thermal ablation and is more likely to occur in lesions with a distance ≤2 cm from the phrenic nerve; however, most phrenic nerve injuries can be recovered. To effectively avoid injury, it is essential to have a thorough knowledge of phrenic nerve anatomy, choose a proper ablation approach, and use assistive techniques, such as artificial pneumothorax or artificial pleural effusion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Chu KF, Dupuy DE. Thermal ablation of tumours: Biological mechanisms and advances in therapy. Nat Rev Cancer 2014;14:199–208.  Back to cited text no. 1
    
2.
Vogl TJ, Nour-Eldin NA, Albrecht MH, Kaltenbach B, Hohenforst-Schmidt W, Lin H, et al. Thermal ablation of lung tumors: Focus on microwave ablation. Rofo 2017;189:828–43.  Back to cited text no. 2
    
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Yang X, Ye X, Lin Z, Jin Y, Zhang K, Dong Y, et al. Computed tomography-guided percutaneous microwave ablation for treatment of peripheral ground-glass opacity-Lung adenocarcinoma: A pilot study. J Cancer Res Ther 2018;14:764–71.  Back to cited text no. 3
    
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Nelson DB, Tam AL, Mitchell KG, Rice DC, Mehran RJ, Sepesi B, et al. Local recurrence after microwave ablation of lung malignancies: A systematic review. Ann Thorac Surg 2019;107:1876–83.  Back to cited text no. 4
    
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Thornton RH, Solomon SB, Dupuy DE, Bains MS. Phrenic nerve injury resulting from percutaneous ablation of lung malignancy. AJR Am J Roentgenol 2008;191:565–8.  Back to cited text no. 5
    
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Fell SC. Surgical anatomy of the diaphragm and the phrenic nerve. Chest Surg Clin N Am 1998;8:281–94.  Back to cited text no. 6
    
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Ye X, Fan W, Wang Z, Wang J, Wang H, Wang J, et al. Expert consensus on thermal ablation therapy of pulmonary subsolid nodules (2021 Edition). J Cancer Res Ther 2021;17:1141–56.  Back to cited text no. 7
    
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Suzuki K, Koike T, Asakawa T, Kusumoto M, Asamura H, Nagai K, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751–6.  Back to cited text no. 8
    
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Saji H, Okada M, Tsuboi M, Nakajima R, Suzuki K, Aokage K, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): A multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet 2022;399:1607–17.  Back to cited text no. 9
    
10.
Matsui Y, Hiraki T, Gobara H, Uka M, Masaoka Y, Tada A, et al. Phrenic nerve injury after radiofrequency ablation of lung tumors: Retrospective evaluation of the incidence and risk factors. J Vasc Interv Radiol 2012;23:780–5.  Back to cited text no. 10
    
11.
Gao X, Tian Z, Cheng Y, Geng B, Chen S, Nan Q. Experimental and numerical study of microwave ablation on ex-vivo porcine lung. Electromagn Biol Med 2019;38:249–61.  Back to cited text no. 11
    
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Sebek J, Taeprasartsit P, Wibowo H, Beard WL, Bortel R, Prakash P. Microwave ablation of lung tumors: A probabilistic approach for simulation-based treatment planning. Med Phys 2021;48:3991–4003.  Back to cited text no. 12
    
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Aquino SL, Duncan GR, Hayman LA. Nerves of the thorax: Atlas of normal and pathologic findings. Radiographics 2001;21:1275–81.  Back to cited text no. 13
    
14.
Loukas M, Du Plessis M, Louis RG Jr, Tubbs RS, Wartmann CT, Apaydin N. The subdiaphragmatic part of the phrenic nerve-Morphometry and connections to autonomic ganglia. Clin Anat 2016;29:120–8.  Back to cited text no. 14
    
15.
Solomon SB, Thornton RH, Dupuy DE, Downey RJ. Protection of the mediastinum and chest wall with an artificial pneumothorax during lung ablations. J Vasc Interv Radiol 2008;19:610–5.  Back to cited text no. 15
    
16.
Lin ZY, Li YG. Artificial pneumothorax with position adjustment for computed tomography-guided percutaneous core biopsy of mediastinum lesions. Ann Thorac Surg 2009;87:920–4.  Back to cited text no. 16
    
17.
Wang Y, Zhang L, Li Y, Wang W. Computed tomography-guided percutaneous microwave ablation with artificial ascites for problematic hepatocellular tumors. Int J Hyperthermia 2020;37:256–62.  Back to cited text no. 17
    
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Delmas L, Koch G, Cazzato RL, Weiss J, Auloge P, Dalili D, et al. Artificial ascites using the guidewire technique during microwave ablation in the liver dome: Technique and analysis of fluid repartition. Abdom Radiol (NY) 2021;46:4452–9.  Back to cited text no. 18
    
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Wu S, Li X, Yu J, Yu X, Cheng Z, Liu F, et al. Ultrasound-guided percutaneous microwave ablation assisted by a three-dimensional visualization preoperative treatment planning system for larger adrenal metastasis (D≥4 cm): Preliminary results. J Cancer Res Ther 2019;15:1477–83.  Back to cited text no. 19
    
20.
Zhang D, Liang P, Yu X, Cheng Z, Han Z, Yu J, et al. The value of artificial pleural effusion for percutaneous microwave ablation of liver tumour in the hepatic dome: A retrospective case-control study. Int J Hyperthermia 2013;29:663–70.  Back to cited text no. 20
    
21.
Morisaki S, Nishi M, Fujiwara H, Oda R, Kawata M, Kubo T. Endogenous glucocorticoids improve myelination via Schwann cells after peripheral nerve injury: An in vivo study using a crush injury model. Glia 2010;58:954–63.  Back to cited text no. 21
    
22.
Chao MV. Neurotrophins and their receptors: A convergence point for many signalling pathways. Nat Rev Neurosci 2003;4:299–309.  Back to cited text no. 22
    


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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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