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Ann Thorac Surg 2004;77:1911-1915
© 2004 The Society of Thoracic Surgeons

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Original article: general thoracic

Video-assisted thoracic surgery for pure ground-glass opacities 2 cm or less in diameter

^a Department of Thoracic Surgery, Toranomon Hospital, Tokyo, Japan

Accepted for publication December 2, 2003.

^* Address reprint requests to Dr Yamada, Tokai University Hachioji Hospital, 1838 Isikawa, Hachioji, Tokyo, 192-0032 Japan
e-mail: yamada.shunsuke{at}hachioji-hosp.tokai.ac.jp

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
BACKGROUND: Small, well-circumscribed pure ground-glass opacities on high-resolution computed tomography can represent either localized bronchioloalveolar carcinoma without foci of active fibroblastic proliferation, or atypical adenomatous hyperplasia. Since neither lesion displays lymph node metastasis, excellent prognosis can be expected even with limited surgical resection. In this study, video-assisted thoracic surgery was performed for patients with pure ground-glass-opacity to evaluate efficacy for both diagnostic and therapeutic purposes.

METHODS: Thirty-nine patients with pure ground-glass opacity less than or equal to 2 cm in diameter (62 lesions) underwent video-assisted thoracic surgery with wedge resection as primary therapy. Histologic diagnoses were made according to Noguchi classifications.

RESULTS: Single lesions were observed in 30 patients, with multiple lesions (mean, 4 lesions) in 9 patients. Twenty-eight patients underwent wedge resection. Seven patients underwent lobectomy or segmentectomy for technical reasons. Four patients underwent conversion of wedge resection to lobectomy (due to active fibroblastic proliferation in 2 patients, and other reasons in 2 patients). All procedures were performed under videoscopic observation. Histologic diagnoses comprised localized bronchioloalveolar carcinoma without active fibroblastic proliferation either alone or in combination with atypical adenomatous hyperplasia in 29 patients, atypical adenomatous hyperplasia in 8 patients, and localized bronchioloalveolar carcinoma with active fibroblastic proliferation in 2 patients. All patients with localized bronchioloalveolar carcinoma underwent follow-up for a median period of 29.3 months, and have survived without sign of recurrence.

CONCLUSIONS: Video-assisted thoracic surgery may be appropriate for management of small pure ground-glass opacities.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Recent advances in radiologic investigation, particularly with the introduction of helical computed tomography (CT) for diagnosis of lung cancer, have resulted in the increased detection, in Japan, of small ground-glass opacities (GGOs) not visualized on conventional radiography. Atypical adenomatous hyperplasia (AAH) is considered representative of premalignant neoplasia, while small-sized localized bronchioloalveolar carcinoma (LBAC) is considered to represent in situ adenocarcinoma. Both tumors present as pure GGO on high-resolution CT (HRCT), and the present paper discusses the efficacy of limited surgical resection of these radiologic features [1–6, 19]. In 1995, Noguchi and colleagues [7] reported the histologic classification of 236 surgically resected peripheral-type adenocarcinomas ( 2 cm in diameter) into 5 groups (Noguchi types A–F) according to pattern of tumor growth. Degree of malignancy was then retrospectively analyzed according to frequency of lymph node metastasis and prognosis. According to this unique classification, type A lesions represent well-differentiated LBAC without fibrotic foci. Type B resembles type A, but fibrotic foci are present due to alveolar collapse. Type C also displays a replacement growth pattern, but with foci of fibroblastic proliferation. Types D–F represent small advanced adenocarcinoma with unfavorable prognosis. Based on this study, small LBAC without foci of active fibroblastic proliferation (type A or B) are considered less invasive. These lesions do not display lymph node metastasis, and are associated with excellent prognosis (100% 5-year survival). These groups of tumors can thus be considered as representing in situ adenocarcinoma, and limited surgical resection is appropriate. Conversely, the characteristics of small LBAC with foci of active fibroblastic proliferation (type C) resemble those of small adenocarcinoma, with regard to both rate of lymph node metastasis (24.5%) and prognosis (74.8% 5-year survival). Radiologic findings of GGO, indicating a BAC component, reportedly represent a positive prognostic factor [5, 8], and GGO findings on HRCT correlate well with Noguchi classifications [5]. On the basis of these earlier investigations, the present study utilized criteria of well-circumscribed nodules less than or equal to 2 cm in diameter, with greater than or equal to 98% GGO content on HRCT for presumptive diagnosis of AAH or LBAC without foci of active fibroblastic proliferation. Video-assisted thoracic surgery (VATS) was performed prospectively in 39 patients, with limited resection as the primary therapy. The diagnostic and therapeutic efficacy of management using VATS for patients displaying small pure GGO on HRCT is discussed.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Between January 2000 and February 2002, VATS was performed for 39 patients with 62 well-circumscribed nodules less than or equal to 2 cm in diameter, with greater than or equal to 98% GGO content on HRCT. To exclude findings of GGO attributable to inflammation, follow-up of GGO was undertaken for at least three months, and VATS resection was planned if lesion size or density increased or remained unchanged. Patients displaying GGO in combination with nodular-type lung cancer were excluded from this study. With the exception of cases involving superficial parenchymal GGO, preoperative percutaneous CT-guided marking using a VATS marker was undertaken for one or two areas on the day before surgery. Wedge resection with VATS was performed as primary therapy. However, in cases with multiple GGO confined to a single lobe or GGO located deep in the lung hilum, VATS segmentectomy or VATS lobectomy was performed from the start, for technical reasons. In cases involving wedge resection, all resected specimens underwent intraoperative frozen examination to confirm the presence of LBAC without active fibroblastic proliferation (type A or B) or AAH. If examination of the GGO lesion led to a suspicion of LBAC with active fibroblastic proliferation (type C), converted VATS lobectomy was performed. Regional lymph node sampling was undertaken in all cases of segmentectomy or lobectomy. Final diagnosis was determined by further histopathological examinations, and all pathologic diagnoses were made according to Noguchi classifications [7].

VATS procedures
All procedures were performed using three access ports (10-, 10-, and 11.5-mm diameters) without minithoracotomy. The VATS wedge resection was performed using an end-stapler, or resection and suturing techniques. In lobectomy or segmentectomy, the end-stapler was used to staple the hilar bronchus and vessels after dissection. In segmentectomy, intersegmental parenchyma was stapled using an end-stapler. Finally, one of the three wounds was extended by 2 to 4 cm to remove specimens.

Follow-Up
All patients underwent follow up in our clinic every 6 months using CT.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Single lesions were identified in 30 patients, with multiple lesions (mean, 4 lesions; range, 2 to 7 lesions) in nine. One patient with multiple lesions displayed bilateral disease. Patient characteristics are listed in Table 1. All patients were asymptomatic, with GGO detected on helical CT during screening for lung cancer, or on CT investigation of other conditions. Preoperative percutaneous CT-guided localization using VATS markers was performed for 39 GGOs in 30 patients (77%). No serious complications resulted from the VATS marking procedure. The VATS procedures are shown in Table 2. Wedge resection was performed in 28 patients, with three of the 28 patients requiring additional wedge resection during the same operation to establish adequate surgical margins. All three cases involved single GGOs 10 mm in diameter, were located less than 3 cm from the pleural surface, and were placed according to previous localization under CT guidance. Two of the three cases exhibited severe pleural adhesions. Four patients underwent segmentectomy for deep pulmonary lesions. Lobectomy was performed in 3 patients with multiple GGOs (2 patients) or GGO located in the lung hilum (1 patient).

Complications and outcomes
One patient (2.6%) underwent reoperation (VATS segmentectomy) for a missing GGO that had been detected postoperatively by CT as one of two GGOs. Air leakage (> 6 days) developed in three patients with massive pleural adhesion, but all patients who underwent VATS displayed uneventful postoperative courses. Mean duration of follow-up for patients with LBAC was 29.3 months (range, 12 to 41 months). As of the time of writing, all patients remain alive and no recurrence of disease has been observed.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Recently, cases of small LBAC presenting with GGO have increased in Japan, due to the introduction of helical CT in screening for lung cancer. The present paper discusses the efficacy of limited surgical resection of LBAC, presenting as pure GGO on HRCT [1–6, 19]. Regarding surgical treatment of peripheral lung cancer, small tumor size alone does not represent a sufficient indication for limited surgery. Even small-sized tumors have the potential for mediastinal lymph node metastasis, and lobectomy with systemic lymph node dissection is considered standard procedure for many cases of nonsmall cell lung carcinoma (NSCLC) [9, 10]. Patients with early stage BAC are often regarded as displaying a better prognosis and less invasive disease than NSCLC at a similar stage [11–13]. The revised World Health Organization (WHO) classification of lung tumors categorizes BAC as a subtype of adenocarcinoma, described as a form of bronchiolar alveolar replacement growth pattern without evidence of invasive components, including stromal, vascular or pleural invasion. Conversely, tumor with evidence of an invasive component is classified as adenocarcinoma with bronchioloalveolar component [14]. However, no concept of peripheral adenocarcinoma in situ is described in the WHO classification, and lobectomy and systemic lymph node dissection are still performed in many cases [11–13]. In 1995, Noguchi and colleagues [7] indicated the presence of in situ carcinoma on the basis of the unique histologic classification of peripheral adenocarcinoma less than or equal to 2 cm in diameter, according to tumor growth pattern, and suggested the possibility of limited surgical resection for in situ carcinoma. The Noguchi classification categorizes LBAC less than or equal to 2 cm in diameter into types A, B, and C. The presence of active fibroblastic proliferation in the area of bronchioloalveolar replacement growth is considered representative of poorer prognosis. The LBAC without foci of active fibroproliferation (type A or B) is considered representative of in situ carcinoma. Conversely, LBAC with foci of active fibroproliferation (type C) is considered to exhibit the characteristics of peripheral adenocarcinoma.

With recent advances in technology, tumors exhibiting a bronchioloalveolar replacement growth pattern can present as GGO on HRCT, with the extent of GGO correlating well with Noguchi classifications of BAC [5]. Small, well-circumscribed and pure GGO on HRCT is considered to represent either AAH or LBAC without foci of active fibroproliferation (type A or B). Conversely, mixed-typed GGO on HRCT is considered indicative of LBAC with foci of active fibroproliferation (type C), and a presumptive preoperative diagnosis of in situ adenocarcinoma can be made accordingly. However, no persuasive data clearly dividing pure GGO and mixed-type GGO have been presented. Ground-glass opacity suspected as representing AAH or LBAC without foci of active fibroblastic proliferation (type A or B) might therefore also comprise LBAC with foci of active fibroblastic proliferation (type C). Histologic confirmation of tumor type during surgery is thus essential. In this study, histologic diagnoses of LBAC with foci of active fibroproliferation (type C) were obtained for two patients displaying GGO. Both tumors were small, measuring less than or equal to 15 mm in diameter, and both demonstrated HRCT findings similar to those seen in LBAC without foci of active fibroproliferation (type A or B). Regarding the clinical features of BAC, 8 of 39 patients (20%) displayed multiple LBACs (type A or B). Since these represented small and separate lesions without hilar or pleural involvement, multifocality caused by lymphatic spread or intrapulmonary aspiration seems highly unlikely. Barskey and colleagues [15] reported evidence of synchronous or metachronous multifocality of BAC as the basis of multicentric development with multiclonal BAC. Limited resection can offer an adequate surgical procedure for obtaining cure, and lobectomy should be avoided to maximize preservation of the lung. In this study, six of seven patients who had a history of lobectomy for lung cancer developed LBAC without foci of active fibroproliferation (type A or B) as second primary lung cancers. However, these new lesions differed histologically from the original primary lung cancers (although histologic diagnosis was unknown in one patient), and none of the patients displayed any sign of recurrence other than GGO. These cases could be expected to result in surgical curability with preservation of lung function. From the perspective of quality of life, VATS represents an almost ideal approach, as thoracotomy is painful and more invasive. The VATS wedge resections for small pulmonary nodules including GGO have recently been proposed. Preoperative marking procedures allow tumor localization, and the probability of missing tumor resection is 0% to 5% [16–18]. However, in these studies, excision of a lesion using VATS is restricted to shallow fields in the pulmonary parenchyma. Deep or multiple GGOs that might require segmentectomy or lobectomy were a common factor for an indication of thoracotomy. In this study, VATS resection was applied to every pure GGO, including cases with multiple lesions, lesions deep in the pulmonary parenchyma, or severe pleural adhesions. Reoperation for a missing lesion was needed in one patient (2.6%) but this lesion was also resected by VATS segmentectomy. The high total rates of additional wedge resection (in the same surgical process, 7.7%) and reoperation are considered as significant morbidities associated with VATS. However, detection and wedge resection of these small GGOs, particularly deep in the pulmonary parenchyma, is difficult even using open thoracotomy. Unlike solid tumors, tumors presenting as pure GGO maintain alveolar structures, and tissue density is therefore low. If these tumors are small and located deep in the parenchyma, palpation is of limited value. In some reports, preoperative localization procedure for pure GGO (mean diameter, 12.3 mm) was undertaken in 38% of patients for surgical wedge resection under thoracotomy [2]. In our experience, wide wedge resection or segmentectomy using CT-guided marking allows safe resection of deep GGO with adequate surgical margins in VATS procedures, although VATS lobectomy remains an option in some cases. Considering only the final pathologic findings, limited resection was compatible with pure GGO less than or equal to 2 cm in diameter in 37 patients (95%), while two patients (5%) exhibited LBAC with foci of active fibroproliferation (type C), and required lobectomy with lymph node assessment. In this study, median duration of follow-up was only 29.3 months, but most recurrences of NSCLC occur within the first 2 years after limited resection [9]. However, all 39 patients remain alive and no tumor recurrence has been observed. Complete resection of all 62 GGOs, according to tumor nature, and the absence of tumor recurrence in all 39 patients supports the feasibility of VATS for managing patients displaying small pure GGO.

In any case, the size of the subject population and duration of follow-up was insufficient to properly determine the effectiveness of VATS managements for these lesions. Further studies addressing these issues should be encouraged to determine the adequacy of VATS limited resection for lesions appearing as pure GGOs on HRCT.

	References

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