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Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan
* Address correspondence to Dr Asamura, Division of Thoracic Surgery, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan (Email: hasamura{at}ncc.go.jp).
Presented at the Minimally Invasive Thoracic Surgery Summit, New York, NY, June 8–9, 2007.
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Introduction |
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 Top Introduction Roentgenologic Definition of...Pathobiologic Nature of Ground...Interventions for Ground-Glass...AcknowledgmentsReferences |
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The pathologic features of these tumors are also characterized by nonmucinous, bronchioloalveolar carcinoma (BAC) or atypical adenomatous hyperplasia (AAH) according to the histologic classification of the World Health Organization (WHO) [5]. A demographic analysis of GGO-BAC tumors indicated that these tumors are more likely to arise in women in their 50s and 60s without a history of smoking. The rate of growth is generally slow, and tumors are even indolent for more than 10 years in some cases. A superb prognosis has been reported in case series from many institutions; to date however, a prospective study that compares the prognosis of lobectomy and limited, sublobar resection for GGO tumors not been reported.
The ultimate purpose of surgical resection for malignant tumor is to ensure the complete clearance of tumor cells. For tumors with invasive growth, the extent of resection is increased so that no tumor cells are left behind, which is called "radical resection." For tumors without invasive growth or with only minimal invasion, however, local excision of the lesion might be permitted. Although the standard mode of resection for lung cancer has been lobectomy, the possibility of limited, sublobar resection for small, faint tumors with GGO appearance is being considered.
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Roentgenologic Definition of Ground-Glass Opacity |
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TopIntroductionRoentgenologic Definition of...Pathobiologic Nature of Ground...Interventions for Ground-Glass...AcknowledgmentsReferences |
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There are two characteristic features of GGO appearance. First, the lesion should be localized or focal, and the diffuse ground-glass appearance in interstitial pneumonitis is not usually included in this category. Second, GGO lesions are characterized by a slight-to-mild increase in CT density that does not obscure preexisting lung structures such as blood vessels and bronchi. When the shape of the pulmonary vessels in the nodules is not recognized in the nodule, the lesion is no longer considered a GGO and instead is called a "solid" lesion.
A GGO lesion can be either homogeneous or heterogeneous. The heterogenous GGO lesion contains a solid, cystic, or linear part inside the nodule. The solid part is located in the center of the nodule and surrounded by the GGO part, which is a so-called fried egg appearance. The solid part might be scant or prominent with various proportions of solid to GGO parts. According to the combination of these two parts, GGO lesions could be classified as nonsolid GGO (homogeneous transparent density without any solid part) and partly solid GGO (complex lesion with both GGO and solid part; Fig 1).
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Pathobiologic Nature of Ground-Glass Opacity Lesions |
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The relationship between CT appearance and histology has been studied [6–8]. Most nonsolid GGOs are AAH or BAC. Invasive growth is rarely seen in the pathology of nonsolid GGO. On the other hand, most partly solid GGOs are BAC and adenocarcinoma with mixed subtypes. The solid lesion usually exhibits invasive growth and is diagnosed as adenocarcinoma with mixed subtypes. Although the image findings on high-resolution CT cannot precisely reveal the pathology with special reference to invasive growth of the tumor, the value of high-resolution CT should be addressed.
Several investigators have studied the pathobiologic background of GGO-BAC tumors [9, 10]. An interesting finding is that GGO-BAC tumors are more likely to arise in nonsmoking women in their 50s and 60s. They also tend to be multicentric, both synchronously and heterochronously. Also of interest is that some nonsolid GGOs have been followed-up for more than 10 years without any intervention, and there has been no overt growth (Fig 2). In contrast, some show overt growth with consolidation (Fig 3). These observations indicated that GGOs do not always grow or they only grow slowly, and as a result, they are indolent for considerably long periods. These observations also showed that GGOs with a smaller size or with a scarce solid component tend to be stable in size, and GGOs in patients with a history of lung cancer tend to grow faster. Other factors that may affect the growth of GGO tumors need to be defined in future studies.
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Interventions for Ground-Glass Opacity-Bronchioloalveolar Carcinoma Tumors |
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TopIntroductionRoentgenologic Definition of...Pathobiologic Nature of Ground...Interventions for Ground-Glass...AcknowledgmentsReferences |
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Nakamura and colleagues [14] performed a meta-analysis on 14 studies that compared the outcome of limited resection and lobectomy for stage I lung cancer [14]. In these 14 studies, the Lung Cancer Study Group (LCSG) study was the sole randomized phase III study, and all of the others were nonrandomized. The meta-analysis showed a combined survival difference (survival rate with lobectomy minus that with limited resection) at 1, 3, and 5 years after resection of 0.7%, 1.9%, and 3.6%, respectively. None of these survival differences were significant, indicating that survival after limited resection for stage I lung cancer was comparable with that after lobectomy. Most of the studies in this meta-analysis were nonrandomized and had a heterogeneous background, and we cannot exclude various biases even with a meta-analytical statistical method.
The possibility of sublobar resection for GGO-BAC tumors seems to be realistic, however, considering the noninvasive or minimally invasive nature of the tumors. Many reports, mainly from Japan, have stated that long-term survival after sublobar resection was equivalent to that after lobectomy for GGO tumors. Superb survival was also documented for noninvasive BAC. It is still unclear whether these outcomes are related to some special nature of tumors in the Japanese population. The general applicability of these results to other populations of patients, particularly those in the West, will require further study of similar tumors in such populations. However, considering the close relationships between the invasive features of the tumor and the prognosis, a better prognosis might also be expected for noninvasive GGO-BAC tumors despite ethnic differences.
In determining the mode of surgical resection, several important factors may have to be considered: tumor location (outer vs inner part of lung parenchyma), tumor size, and nature of the tumor (nonsolid vs partly solid vs solid).
Considering the indolent nature of small nonsolid GGOs tumors with a diameter of less than 15 mm, careful monitoring without intervention should be chosen, in our opinion based on anecdotal experiences. These tumors are less likely to grow fast between CT scans as tumors disseminate in distant organs. We can also accumulate follow-up data on GGO tumors without any intervention. Overt growth or overt consolidation might be an indication for surgical intervention. For tumors larger than 15 mm in diameter, a wide wedge resection/segmentectomy should be the mode of choice as long as they are located in the outer one-third of the lung parenchyma. Otherwise, there might be no option other than lobectomy. For partly solid GGOs less than 15 mm in diameter, sublobar resection could be performed as well; however, an intraoperative pathologic evaluation to determine invasive features is indispensable. If the tumor shows overt invasive growth, lobectomy should be performed. For tumors with an overt, prominent, solid component, the gold standard, lobectomy, is indicated as usual.
From the present point of view, there are several issues regarding the phase III LCSG study [12]:
Strictly, surgical equivalency between lobectomy and sublobar resection should be studied only by a randomized phase III study. Thus, this study should have a noninferiority design regarding the prognosis (overall survival), and the advantage of sublobar resection regarding postoperative pulmonary function should also be addressed. In this forthcoming study, the number of segments should preferably be limited to fewer than two, regardless of their location. Approach by video-assisted thoracic surgery or open procedure should be permitted, and sampling of the sump node is recommended before resection. Because pure GGO-BAC tumors are already known to have an excellent prognosis, these tumors should be excluded, and instead the study should focus on more advanced invasive tumors smaller than 2 cm in diameter. Although such a study would require more than 1000 cases, the results might revise the standard surgical care for tumors without nodal involvement. Such studies are being planned in both North America and Japan, and the study protocol is being refined.
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Acknowledgments |
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TopIntroductionRoentgenologic Definition of...Pathobiologic Nature of Ground...Interventions for Ground-Glass...AcknowledgmentsReferences |
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References |
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TopIntroductionRoentgenologic Definition of...Pathobiologic Nature of Ground...Interventions for Ground-Glass...AcknowledgmentsReferences |
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  J. M. Goo, C. M. Park, and H. J. Lee Ground-Glass Nodules on Chest CT as Imaging Biomarkers in the Management of Lung Adenocarcinoma Am. J. Roentgenol., March 1, 2011; 196(3): 533 - 543. [Abstract] [Full Text] [PDF]
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 H. Oizumi, N. Kanauchi, H. Kato, M. Endoh, S.-i. Takeda, J. Suzuki, K. Fukaya, and M. Sadahiro Total thoracoscopic pulmonary segmentectomy Eur J Cardiothorac Surg, August 1, 2009; 36(2): 374 - 377. [Abstract] [Full Text] [PDF]
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