|Year : 2015 | Volume
| Issue : 6 | Page : 75-79
The role of video-assisted thoracoscopic surgery in management of the multiple ground-glass nodules
G Shao, W Ren, Z Feng, Z Peng
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021,
Shandong Province, China
|Date of Web Publication||24-Dec-2015|
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province
Source of Support: None, Conflict of Interest: None
Objective: We investigated the outcomes of patients with multiple ground-glass nodules (GGNs) to identify the role of video-assisted thoracoscopic surgery (VATS) in diagnosis and treatment. Patients and Methods: We included patients with multiple GGNs who were qualified for thoracoscopic surgery resection and analyzed the statistics. Results: Fifty-one GGNs were detected in 21 patients. There were 40 pure GGNs and 11 part-solid ones. Around 46 of the 51 lesions were resected via VATS. Four pure GGNs <10 mm and deep in the lung were proceeded with continuous follow-up. One pure GGN measuring 16 mm considered as subnodule and also deep in the lung underwent stereotactic ablative radiotherapy. Resection methods included lobectomy (1), segmentectomy (1), lobectomy + segmentectomy (6), lobectomy + wedge resection (10), and segmentectomy + wedge resection (3). Of the 46 resected lesions, 4 (8.7%) were atypical adenomatous hyperplasia (AAH), 23 (50%) were adenocarcinoma in situ(AIS), 15 (32.7%) were minimally invasive adenocarcinoma (MIA), 2 (4.3%) were invasive adenocarcinoma, one was pulmonary sclerosing hemangioma, and one was nonspecific fibrosis. Intersegmental lymph node metastasis was found in one of the 21 patients. No postoperational complication occurred in any of the patients. Conclusion: Multiple GGNs were generally independent primary lung cancers, mainly including AAH, AIS, MIA, rather than intrapulmonary metastasis. VATS was superior to thoracotomy for less invasive and shorter hospital stay.
Keywords: Lobectomy, multiple ground-glass nodules, primary lung cancers, sublobectomy, video-assisted thoracoscopic surgery
|How to cite this article:|
Shao G, Ren W, Feng Z, Peng Z. The role of video-assisted thoracoscopic surgery in management of the multiple ground-glass nodules. Indian J Cancer 2015;52, Suppl S2:75-9
|How to cite this URL:|
Shao G, Ren W, Feng Z, Peng Z. The role of video-assisted thoracoscopic surgery in management of the multiple ground-glass nodules. Indian J Cancer [serial online] 2015 [cited 2021 Jun 22];52, Suppl S2:75-9. Available from: https://www.indianjcancer.com/text.asp?2015/52/6/75/172518
| » Introduction|| |
With the widespread use of low-dose helical computed tomography (LDCT) in lung cancer screening, an increasing number of pulmonary faint lesions termed ground-glass nodules (GGNs) are detected. GGNs are defined as lesions of homogenous and hazy increase in density without a solid component or contain both ground-glass and solid parts known as part-solid GGNs.,, Many studies indicate that it is not unusual for clinicians to encounter multiple GGNs.,, It is important to diagnose whether those nodules are malignant or benign; primary lung cancer or intrapulmonary metastasis. Benign GGNs may be observed as nonspecific fibrosis, organizing pneumonia, inflammation, local hemorrhage, and so forth.,,, However, several investigators reported that GGNs with an initial size >10 mm, persistent, increasing in size, or with an appearance of solid component had a high possibility of malignancy.,, Moreover, Chang et al. demonstrated that GGNs with size >10 mm appears to be a risk factor for growth. National Comprehensive Cancer Network (NCCN) Guidelines version 2.2015 recommends biopsy or surgical excision for GGNs that are suspicious for malignancy after scheduled follow-up. Moreover, surgical resection of GGNs is also recommended as principle method of diagnosis, according to American College of Chest Physicians (ACCP) guidelines., CT-guided fine needle aspiration lung biopsy (CT-FNA) as another diagnostic method has also been reported in several studies. Although a series of relevant studies reported that most surgically resected nodular ground-glass opacity (GGO) nodules were atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), there is still an absence of randomized data, especially about the surgical method.,,, And, CT-FNA as an invasive way with false negative possibility is not be considered as an appropriate diagnostic way for multiple lesions. Video-assisted thoracoscopic surgery (VATS) as a method for managing a single malignant GGN had proved to valid., Mun and Kohno reported that multifocal wedge resection or lobectomy via VATS provided satisfactory results for patients with multiple GGNs representing bronchioloalveolar cell carcinomas. However, the diameter of GGNs involved in their study was equal or <20 mm, and the nodules were all pure GGNs. In this study, we evaluated the outcomes of patients who underwent multiple pulmonary GGNs (including the ones >20 mm) resection via VATS, aiming to investigate its value for diagnosis and management of multiple GGNs and trying to contribute to the clinical work.
| » Patients and Methods|| |
From March 2013 to May 2015, a total of 21 qualified patients (13 men, 8 women; mean age, 54 years; age range, 43–78 years) with multiple GGNs underwent VATS without any preoperative adjuvant therapy in our hospital. All the patients had at least two GGNs in a different or same lobe in the ipsilateral or bilateral lung with the use of high-resolution CT. The patients had been scheduled for follow-up by LDCT before undergoing surgical procedure according to NCCN Guidelines version 2.2015 for lung cancer screening. Patients who satisfied the following criteria were included in the study. (1) Patients with persistent nodules. (2) Patient with nodules increasing in size (increase in mean diameter >2 mm or in the solid portion). (3) Patients with development of solid components. This study was approved by the Institutional Review Board of our Shandong Provincial Hospital Affiliated to Shandong University and but written informed consent was acquired from all patients.
Computed tomography scanning and evaluation
During the follow-up period, serial CT scans (at thin slices <1.5 mm) were obtained from the image department of our hospital. We used low-dose, noncontrast, and thin sections to monitor nodules of interest with the aim to find any solid part in time. If mediastinal abnormalities or lymph node were found in the following circumstances, the patients would undergo CT surveillance with standard dose and intravenous contrast. The surveillance principle and follow-up interval were made according to NCCN guidelines. (1) Patients with pure GGNs ≤5 mm in diameter underwent LDCT scan at 12 months. (2) Patients with pure GGNs >5 mm underwent LDCT scan at 6 months. If a solid part appeared, CT scan interval would be reduced to 3 months, or the patients directly went to surgery. (3) Patients with part-solid GGNs underwent LDCT scan at 3 months, if the nodules were persistent or increased in size, no matter if the GGNs were pure or part-solid, surgical intervention would proceed. With regards to the results of previous studies, GGNs >10 mm is a risk of growth and malignancy, for patients with GGNs, pure or not, measuring >10 mm in diameter at the initial LDCT scans, surgery resection was recommended to the patients if patient consent was obtained.
Before the operation, all patients underwent a physical examination, a CT scan of the brain, chest, and abdomen with intravenous contrast. The details of surgical procedure were determined according to the size and number of lesions, preoperative respiratory and cardiovascular function assessment, the presence of comorbidities and intraoperative frozen pathological results. (1) For patients with synchronous lesions in an ipsilateral chest, we resected the multiple lesions by single-stage VATS via a single-port (midaxillary line in the fifth intercostals space) or two-port (midaxillary line in the seventh or eighth intercostal space for video camera and anterior axillary line or midaxillary line in the fourth or fifth intercostal space for instruments) approach. If all nodules were located in bilateral upper lobes of the lung, VATS via subxiphoid single port was adopted. When the sites were in bilateral chest but were not all in upper lobes, unless patients had adequate estimated postoperative respiratory function to tolerate the surgical resection, we converted the single-stage surgical treatment to two-stage resection or left the remaining ones to proceed with stereotactic ablative radiotherapy (SABR) as an alternative. (2) (a) When the lesions were >30 mm, we performed lobectomy if patients were not left with elevated surgical risk. (b) Nodules ranging from 20 mm to 30 mm or part-solid GGNs <30 mm in diameter underwent segmentectomy and intersegmental lymph node dissection. If the lesions were located deep in the lung, lobectomy proceeded as an alternative. (c) Pure GGNs ranging from 10 mm to 20 mm and located in the outer third of the lung underwent wedge resection. When the lesions were located deep in the lung, if they were the main nodules, lobectomy would be performed, and if they were sub-nodules, continuous monitoring or SABR would be done. (d) For pure GGNs <10 mm, wedge resection was adopted. If they were deep in the lung, we decided not to select resection or SABR and instead just chose continuous follow-up. (3) All patients underwent the N1 and N2 lymph nodes resection or sample for intraoperative frozen section. Intersegmental lymph node frozen section should be obtained in patients undergoing segmentectomy and if node positive for malignancy were found by histologists, segmentectomy would be replaced by lobectomy, given the patients were capable of the enlarged resection. If this was difficult to be conducted, an enlarged resection margin as large as possible should be performed. (4) As to the methods of tumor localization, we mainly used palpation to figure out the target nodules and located those small and low-density lesions that might be nonpalpable with CT-guided Hook wire. (5) We identified the histological stage of the maximum nodule as the stage of the multiple GGNs. The principle of histological stage was determined according to the single 7th edition of the TNM Classification for Lung and Pleural Tumors.
| » Results|| |
Homochronous or two-stage lobectomy or sublobar resection (wedge resection or segmentectomy) via VATS was successfully accomplished in all 21 patients. A total of 51 nodules were detected by CT scan in the patients. 10 nodules were <10 mm in diameter. Five were more than 30 mm. The number of nodules measuring 10–20 mm was 36; measuring 20–30 mm was 15. Patient characteristics are summarized in [Table 1]. Of the 51 GGNs, 40 were pure nodules and 11 were with part-solid involvement. 46 GGNs in 21 patients were removed. Of the 21 patients, 16 underwent completely resection, and five patients were left with a pure nodule, respectively. In five of the patients, four with GGNs <10 mm and deep in the lung proceeded with continuous follow-up. One with a sub-nodule measuring 16 mm in diameter and also deep in the lung underwent SABR [Table 2]. Because lobectomy would be performed to remove the main lesion, the patient was thought to be incapable of lobectomy once more for inadequate estimated postoperative pulmonary function. Resection methods included lobectomy (1), segmentectomy (1), lobectomy + segmentectomy (6), lobectomy + wedge resection (10), and segmentectomy + wedge resection (3). Eighteen patients underwent single-port or two-port VATS through the chest wall. The resection through subxiphoid single port was applied to 3 patients. Of the 46 resected lesions, 4 (8.7%) were AAH, 23 (50%) were AIS, 15 (32.7%) were MIA, and 2 (4.3%) were invasive adenocarcinoma. Besides, benign lesions including pulmonary sclerosing hemangioma (1, 2.2%) and nonspecific fibrosis (1, 2.2%) were also observed. Malignant metastasis of intersegmental lymph node was positive in one case [Table 3]. The GGNs of the four patients with a history of previous malignancy were proved to be primary lung cancer instead of metastasis. The average hospital stays were 9 days. No complication happened to any of the patients. The postoperative CT scans and pulmonary function tests at 3 months displayed a good to excellent outcome in the patients.
|Table 2: Clinical characteristics of the 21 study patients relative to surgery strategy|
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| » Discussion|| |
In this study, almost all of pathological types of the resected GGNs were AAH, AIS, MIA, and merely one case presented lymphatic metastasis. According to the criteria, recommended by Martini and Melamed and ACCP Evidence-based Clinical Practice Guidelines about multiple primary lung cancers, those GGNs confirmed by pathology as AAH, AIS, MIA, and without lymphatic metastasis were considered as distinct primary disease clones., Our results showed that multiple GGNs were usually independent, noninvasive, heterogeneous lesions rather than intrapulmonary metastasis, suggesting that most multifocal GGNs have a favorable prognosis and limited resection should be recommended, which is consistent with several previous studies.,,,, In this study, GGNs of the four patients with a history of previous malignancy were also proved to be primary lung cancer. However, three other studies we found reported that a history of whether primary lung cancer or extrapulmonary malignancy was a risk of GGN growth and malignancy. Thus, it was critical to pay adequate caution to such patients aiming to avoid over- or under-diagnosis.
Several studies had reported the correlation between the CT features of nodular GGO and their pathology. Persistent findings, increasing in size of GGNs at CT may be strongly suggestive of neoplastic diseases, such as AAH, AIS, and MIA, especially if the lesion includes a solid component., Moreover, when GGNs with a solid portion demonstrated the following features at CT, such as spiculations, pleural retraction, or bronchovascular bundle thickening, they may be invasive adenocarcinoma with a high possibility. In addition, when clinicians evaluated the likelihood of malignancy, relative risks of patients, such as age, history of smoking, family history of lung cancer, nodule size, growth rate during follow-up period, and radiologic characteristics should also be taken into consideration.
However, there is still an absence of definite methods to diagnose whether the lesions are malignant or benign preoperatively, despite the report that the accuracy of CT-FNA was as high as 80%. Positron emission tomography-CT is also not adopted as a preoperative diagnostic method because of its poor elevated fluorodeoxyglucose activity in subcentimeter invasive nodules and negative elevation in AIS., Other modalities, such as sputum cytology and endobronchial or transbronchial biopsy are also not universally accepted because of its uncertain and invasive features. In the current studies, surgical resection remains to be the optimal option, which meets both diagnostic and therapeutic requirements at the same time.
Compared with traditional surgery method, VATS approach can also remove the lesions, dissect lymph nodes, define the clinical staging, and get enough samples for genomic analyses. Besides, given the promise of surgical tolerance, single-stage bilateral resection is feasible and safe. Especially, the approach of the removal of the nodules located in bilateral upper lobes of the lung via a subxiphoid single port is minimally invasive followed with a short hospital stay.
In the absence of criteria suggesting the range of operation, we recommend patients undergo sublobectomy if (1) cardiopulmonary function of the patients is impaired but capable of withstanding the surgery. (2) The lesions are in the outer third of the lung and are <3 cm in diameter. (3) Hilar lymph nodes and mediastinal lymph nodes are negative in metastasis. With regard to the issue on wedge resection versus segmentectomy, Sienel et al. showed that there was no difference in cancer-specific survival between the group who underwent either wedge resection or segmentectomy and the segmentectomy group, but a lower locoregional recurrent rate in the segmentectomy group was reported in the study (55% vs. 16%; P = 0.001). Based on those data and the allowance for dissection of the intersegmental lymph nodes, we recommend patients with part-solid GGNs or pure GGOs larger than 20 mm and smaller than 30 mm undergo segmentectomy. While for the pure GGOs <20 mm and in the outer third of the lung, wedge resection is considered to be safe. Lesions >30 mm usually cannot be resected via segmentectomy with negative parenchymal margins, and lobectomy will typically offer a substantial benefit over segmentectomy. Several studies have issued that the pure GGO lung nodules did not grow during long-term follow-up, and the growing ones showed an indolent clinical course., The appropriate management for pure GGNs that are small (<10 mm) and deep in the lung is follow-up on a regular basis.
For features that are soft or deep in the lung, the GGNs cannot always be palpable or visible. Localization of those GGOs becomes a technical difficulty of mini-invasive operation resection. Therefore, multiple tumor-localization techniques emerged in response to the need, such as lung surface marking, ultrasonography, hook wire, radioactivity, and so forth. However, such techniques can only locate the site but not the range of lesions, which will result in an inadequate margin of resection. Thus, it would provide a lot of benefits if a randomized clinical trial was performed.
This study has some limitations. First, although 21 patients had been involved in the study, the number was still small, and a large-scale investigation is in need. Second, we distinguished the primary lung cancers from intrapulmonary metastasis with histological results, including AAH, AIS, and MIA. Wu et al., demonstrated that multiple lung GGN synchronous with non-small cell lung cancer (NSCLC) displayed a high heterogeneity in driver mutations with NSCLC. Similarity phenomenon was found in the study of Barsky et al., which reported a multiclonal origin of multifocal bronchioloalveolar lung carcinomas., However, the evidences of multiclonality using genomic analyses were not available. In addition, a regular postoperative surveillance was not conducted yet.
| » Conclusion|| |
According to the results of this study, most of the CT screening-detected GGNs are primary lung cancers rather than intrapulmonary metastasis. A strategy of surgery management and regular surveillance should be considered for patients with multifocal GGNs. Besides, we also found that GGNs in the four patients with a history of previous malignancy were proved to be primary lesions. The four patients underwent surgery resection rather than chemotherapy and were followed with favorable prognosis. Therefore, in the absence of definitive evidence, appropriate follow-up and further investigations, if necessary should be put into practice, which is crucial to the therapeutic strategy option and to avoid excessive chemotherapy. VATS can not only offer the diagnosis and therapy at the same time but is also characterized by a short hospital stay. A single-stage resection of lesions in bilateral upper lobes via subxiphoid port is more convenient and less invasive than traditional surgery method.
| » Acknowledgments|| |
This work was supported by the Science and Technology Progress Project of Shandong Province (2012GGB14047).
| » References|| |
Henschke CI. Early lung cancer action project: Overall design and findings from baseline screening. Cancer 2000;89 11 Suppl: 2474-82.
Gardiner N, Jogai S, Wallis A. The revised lung adenocarcinoma classification – An imaging guide. J Thorac Dis 2014;6 Suppl 5:S537-46.
Naidich DP, Bankier AA, MacMahon H, Schaefer-Prokop CM, Pistolesi M, Goo JM, et al.
Recommendations for the management of subsolid pulmonary nodules detected at CT: A statement from the Fleischner Society. Radiology 2013;266:304-17.
Seidelman JL, Myers JL, Quint LE. Incidental, subsolid pulmonary nodules at CT: Etiology and management. Cancer Imaging 2013;13:365-73.
Barsky SH, Grossman DA, Ho J, Holmes EC. The multifocality of bronchioloalveolar lung carcinoma: Evidence and implications of a multiclonal origin. Mod Pathol 1994;7:633-40.
Godoy MC, Naidich DP. Subsolid pulmonary nodules and the spectrum of peripheral adenocarcinomas of the lung: Recommended interim guidelines for assessment and management. Radiology 2009;253:606-22.
Kim HK, Choi YS, Kim J, Shim YM, Lee KS, Kim K. Management of multiple pure ground-glass opacity lesions in patients with bronchioloalveolar carcinoma. J Thorac Oncol 2010;5:206-10.
Park CM, Goo JM, Lee HJ, Lee CH, Chun EJ, Im JG. Nodular ground-glass opacity at thin-section CT: Histologic correlation and evaluation of change at follow-up. Radiographics 2007;27:391-408.
Lee HJ, Goo JM, Lee CH, Yoo CG, Kim YT, Im JG. Nodular ground-glass opacities on thin-section CT: Size change during follow-up and pathological results. Korean J Radiol 2007;8:22-31.
Nakajima R, Yokose T, Kakinuma R, Nagai K, Nishiwaki Y, Ochiai A. Localized pure ground-glass opacity on high-resolution CT: Histologic characteristics. J Comput Assist Tomogr 2002;26:323-9.
Hara M, Oda K, Ogino H, Oshima H, Sato Y, Kiriyama M, et al.
Focal fibrosis as a cause of localized ground glass attenuation (GGA) – CT and MR findings. Radiat Med 2002;20:93-5.
Chang B, Hwang JH, Choi YH, Chung MP, Kim H, Kwon OJ, et al.
Natural history of pure ground-glass opacity lung nodules detected by low-dose CT scan. Chest 2013;143:172-8.
Shinohara S, Hanagiri T, Takenaka M, Chikaishi Y, Oka S, Shimokawa H, et al.
Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. Radiol Oncol 2014;48:50-5.
Gould MK, Fletcher J, Iannettoni MD, Lynch WR, Midthun DE, Naidich DP, et al.
Evaluation of patients with pulmonary nodules: When is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd
edition). Chest 2007;132 3 Suppl: 108S-30S.
Hur J, Lee HJ, Nam JE, Kim YJ, Kim TH, Choe KO, et al.
Diagnostic accuracy of CT fluoroscopy-guided needle aspiration biopsy of ground-glass opacity pulmonary lesions. AJR Am J Roentgenol 2009;192:629-34.
Yoshida J, Nagai K, Yokose T, Nishimura M, Kakinuma R, Ohmatsu H, et al.
Limited resection trial for pulmonary ground-glass opacity nodules: Fifty-case experience. J Thorac Cardiovasc Surg 2005;129:991-6.
Watanabe S, Watanabe T, Arai K, Kasai T, Haratake J, Urayama H. Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography. Ann Thorac Surg 2002;73:1071-5.
Mun M, Kohno T. Efficacy of thoracoscopic resection for multifocal bronchioloalveolar carcinoma showing pure ground-glass opacities of 20 mm or less in diameter. J Thorac Cardiovasc Surg 2007;134:877-82.
Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg 1975;70:606-12.
Shen KR, Meyers BF, Larner JM, Jones DR; American College of Chest Physicians. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd
edition). Chest 2007;132 3 Suppl: 290S-305S.
Takashima S, Maruyama Y, Hasegawa M, Yamanda T, Honda T, Kadoya M, et al.
CT findings and progression of small peripheral lung neoplasms having a replacement growth pattern. AJR Am J Roentgenol 2003;180:817-26.
MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP, et al.
Guidelines for management of small pulmonary nodules detected on CT scans: A statement from the Fleischner Society. Radiology 2005;237:395-400.
Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP, et al.
Evaluation of individuals with pulmonary nodules: When is it lung cancer? Diagnosis and management of lung cancer, 3rd
ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143 5 Suppl: E93S-120S.
Shrager JB. Approach to the patient with multiple lung nodules. Thorac Surg Clin 2013;23:257-66.
Sienel W, Dango S, Kirschbaum A, Cucuruz B, Hörth W, Stremmel C, et al.
Sublobar resections in stage IA non-small cell lung cancer: Segmentectomies result in significantly better cancer-related survival than wedge resections. Eur J Cardiothorac Surg 2008;33:728-34.
Gulati CM, Schreiner AM, Libby DM, Port JL, Altorki NK, Gelbman BD. Outcomes of unresected ground-glass nodules with cytology suspicious for adenocarcinoma. J Thorac Oncol 2014;9:685-91.
Wu C, Zhao C, Yang Y, He Y, Hou L, Li X, et al.
High discrepancy of driver mutations in patients with NSCLC and synchronous multiple lung ground-glass nodules. J Thorac Oncol 2015;10:778-83.
[Table 1], [Table 2], [Table 3]