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Original Articles: General Thoracic

Helical Computed Tomography Inaccuracy in the Detection of Pulmonary Metastases: Can It Be Improved?

^a Division of Cardiothoracic Surgery, University of North Carolina, Chapel Hill, North Carolina
^b School of Medicine, University of North Carolina, Chapel Hill, North Carolina
^c Department of Radiology, University of North Carolina, Chapel Hill, North Carolina
^d Division of Thoracic Surgery, Yale University School of Medicine, New Haven, Connecticut

Accepted for publication June 25, 2007.

^_* Address correspondence to Dr Parsons, Division of Cardiothoracic Surgery, University of North Carolina, 3040 Burnett-Womack Bldg, CB #7065, Chapel Hill, NC 27599-7065 (Email: alden_parsons{at}yahoo.com).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background: In thoracic surgery, manual lung palpation for detection of pulmonary metastases during resection is the standard of care, despite improvements in computed tomography (CT) imaging. In our previous study based on chart review alone, the accuracy of helical CT in the detection of pulmonary metastases was surprisingly low, with a sensitivity of 78%. We hypothesized that this may be improved by scan interpretation with adequate clinical history and focused documentation of all pulmonary lesions, and may be influenced by the training of the reader.

Methods: Preoperative CT scans of 53 patients undergoing 60 cases of pulmonary metastasectomy at our center from 1996 to 2004 were retrospectively reviewed by a dedicated chest radiologist and a non–chest radiologist. Nodules detected on preoperative helical CT were compared with pathologically confirmed metastases.

Results: In 27 of 59 (46%) cases read by radiologist 1, and 27 of 58 (47%) cases read by radiologist 2, metastases found by lung palpation were not seen on preoperative CT. Preoperative CT was entirely correct (no missed metastases or false-positive lesions) in only 11 of 59 (19%) of cases read by radiologist 1, and 11 of 58 (19%) of cases read by radiologist 2.

Conclusions: Helical CT misses metastases in 46% to 47% of cases. Accuracy of preoperative CT scanning for detection of pulmonary metastases was not improved with the provision of clinical history to the reader, nor was it influenced by the interpreter’s training. A combined approach to pulmonary metastasectomy including preoperative and postoperative CT as well as manual lung palpation is necessary to render the patient disease-free.

	Introduction

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The incorporation of minimally invasive approaches into curative pulmonary metastasectomy has been a matter of some debate. Early literature surrounding the management of isolated metastases to the lungs from a controlled extrathoracic primary tumor demonstrated a survival benefit from resection of pulmonary metastases if a complete resection could be achieved [1–7]. Because of the goal of a complete resection, pulmonary metastasectomy has been performed by most surgeons through open incisions such as sternotomy, clamshell incisions, and bilateral staged thoracotomies to minimize the chance of leaving undetected pulmonary metastases behind.

More recently, the development of video-assisted thoracoscopic surgical techniques has brought the traditional open approach into question. Additionally, advances in thoracic imaging modalities, specifically helical computed tomography (CT) scanning, have further raised the question whether imaging techniques have improved to the point that all pulmonary metastases can be reliably detected preoperatively, making palpation superfluous. This question was first addressed prospectively by McCormack and associates [8] in 1996. Patients were enrolled in a prospective clinical trial in which they underwent video-assisted thoracoscopic surgical resection of pulmonary metastases as detected by preoperative helical CT, then underwent open thoracotomy for palpation. The study was closed after enrollment of only 18 of a planned 50 patients, because 14 of the 18 patients did in fact have additional lesions found at thoracotomy.

Since that study was published, most evidence-based thoracic surgeons have remained committed to open palpation of both lungs as the standard of care for pulmonary metastasectomy. However, thoracic imaging continues to evolve and improve along with minimally invasive techniques. It is therefore incumbent on us to readdress whether we can successfully resect pulmonary metastatic disease with less morbidity for the patient.

We retrospectively reviewed our experience with pulmonary metastasectomy at our tertiary referral university medical center to determine our success at detecting pulmonary metastases by helical CT scanning preoperatively. Our initial retrospective review found that when compared with histologically confirmed metastases detected intraoperatively, preoperative helical CT scanning missed lesions in 22% of patients [9]. Although this was consistent with previously published literature [10–13], we were surprised that newer-generation scanners did not improve the sensitivity of the preoperative imaging. Our subset analysis in the initial study failed to elucidate a reason for the poor accuracy of preoperative CT. Additionally, the concept of missing small nodules is not consistent with CT screening data, which seems to indicate a problem in lack of specificity with the newest-generation scanners, rather than lack of sensitivity.

Accordingly, we designed a more detailed study to determine more specifically why pulmonary metastases were not more accurately detected by preoperative helical CT. Given that our initial study was based on chart review alone, we hypothesized that perhaps helical CT scan accuracy may be influenced by providing adequate clinical history to the radiologist at the time of scan interpretation, as well as the knowledge of the importance of identification of all potential metastases. We also speculated that the specialty chest training of the radiologist might have an effect.

	Patients and Methods

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Patient Selection
This study was approved by our institutional review board, and a waiver of consent obtained because of the retrospective nature of the study. Chart review was performed on all patients undergoing pulmonary metastasectomy and manual lung palpation with curative intent at our tertiary care facility between 1996 and 2004. Patients were included in the study if they had a preoperative helical CT scan available for review. A subset of these patients was part of the previously published review [9].

During the study period, CT scanning technique at our institution did evolve, leading to some variation in technique across the study. Chest CT scans were performed according to standard protocol, using a spiral-acquisition single-breathhold technique, with reconstructed slice thickness ranging from 4 to 10 mm in thickness (15% with 4-mm, 15% with 5-mm, 65% with 8-mm, and 3% with 10-mm slice thickness). All but four scans were performed with intravenous contrast. A multislice CT scanner (Siemens Sensation 16; Siemens, New York, NY) was used for eight scans with a reconstructed slice thickness of 5 mm. The remainder of the CT examinations was performed using a single-slice helical CT scanner. Computed tomographic scans were reviewed by radiologists using two different methods. Scans performed later than March 2001(19 scans total) were reviewed on the hospital PACS system. (AGFA NV, Mortsel, Belgium). Scans before this were only available as hard copy 12 x 1 films (42 scans total), and were read using a light box. Only the axial reconstructed images were used when interpreting the CT scans.

Computed tomographic scans were reviewed independently by a dedicated chest radiologist and by a general radiologist; both were blinded to clinical information other than the nature of the study. Radiologists were asked to perform a lesion-by-lesion analysis for all metastatic lesions specifying their location by lobe and segment. Any lesion thought to be at least suspicious for metastasis was counted as a radiographically identified metastasis. Radiologists were permitted comparison to prior studies when available. Final pathologic data were obtained by chart review of clinical information for each patient, including operative reports and pathology reports for each procedure.

The radiographic analysis was compared with two definitions of metastases: the first was metastases identified at the time of resection, and the second also included metastases defined by nodule progression on follow-up CT scan or subsequent biopsy within the postoperative period. This led to two analyses. Within the first analysis, we compared lesions identified on preoperative CT with nodules palpated, resected, and histologically confirmed to be metastases. The second analysis included the first analysis lesions plus lesions seen on the preoperative CT scan that were not identified at the time of resection but proved to be metastases on follow-up (either follow-up CT scan or subsequent resection). These were metastases called appropriately by the radiologist but missed by the surgeons.

In the first analysis, which was based on CT scan review only, the suspected metastases identified by the radiologists were compared with the actual metastases found intraoperatively and proven in the pathology report. Metastatic lesions identified by both the pathologist and the radiologist in the same lobe were considered true positives, as segmental location was not always provided in the pathology report. Metastatic lesions identified by pathology but not by the radiologists were considered false negatives, and suspected metastases identified by the radiologist but not the pathologist were considered false positives.

The second analysis also included nodules that were considered false positives in the first analysis, but which progressed on postoperative CT scan or were resected in a subsequent procedure. All lesions that grew on follow-up CT within 12 months of the surgery or that were confirmed to be metastases by subsequent surgery were considered recurrences that were missed at the time of the initial surgery. These false-positive nodules that progressed postoperatively were considered recurrent if they were seen postoperatively within the same lobe as the false-positive nodule on the preoperative CT scan, because more-specific segment location was not always available. In the second analysis, the sensitivity and positive predictive values (PPVs) of the radiologists’ interpretations were recalculated to include the subsequent characterization of these lesions.

We also compared radiologic and pathologic findings with respect to the side of involvement (right or left lung). This analysis was performed to determine whether helical CT could be used to spare patients an unnecessary exploration on one side by assessing how often a contralateral lesion not detected by preoperative CT would have been missed if a bilateral approach had not been done.

Statistical Analysis
Statistical analysis was performed using SAS software (SAS Institute Inc, Cary, NC). The individual radiologists’ data were analyzed specifically for sensitivity and PPV. Sensitivity was determined by the number of true-positive metastases identified by the radiologist divided by the number of total metastases identified by pathology (true positives + false negatives). Positive predictive value was determined by the number of true-positive metastases identified by the radiologist divided by the total number of nodules called by the radiologist (true positives + false positives). Ninety-five percent confidence intervals (CI) were calculated for both sensitivity and PPV. These calculations were performed for both the first analysis and the second analysis, resulting in both early and late sensitivities and PPVs for each radiologist. Additionally, results were calculated both on a per lesion basis and a per patient basis. Because a reliable assessment of true negatives was not possible, other test variables such as specificity could not be calculated. Subset analysis including length of time between CT and resection, tumor histology, nodule size, multiple versus single nodules, and disease-free interval was performed in the initial study and was not repeated because none of these factors yielded a subset for which helical CT accuracy was adequate to avoid palpation.

	Results

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Between 1996 and 2004 at The University of North Carolina at Chapel Hill, 53 patients who had undergone pulmonary metastasectomy with curative intent had CT scans available for review. The 53 patients underwent a total of 60 surgical explorations, and all 60 preoperative scans were reviewed by both radiologists. Three cases in which the number of nodules were read (1 case by radiologist 1, and 2 cases by radiologist 2) as multiple or too numerous to count were dropped, leaving 59 scans reviewed by radiologist 1 and 58 scans reviewed by radiologist 2 that were included in the study.

The pathologic diagnoses of the extrathoracic primaries of the entire patient group can be seen in Figure 1. The average age of patients included in the study was 51.5 years (median, 50 years; range, 15 to 83 years). There were 28 men and 25 women. An average of 2.9 nodules was seen preoperatively by both radiologists per case (median, 3; range, 0 to 11). The mean number of metastases confirmed by pathology per case was 2.3 (median, 2; range, 0 to 12). The helical CT scans were obtained an average of 29.6 days before the metastasectomy (median, 26; range, 0 to 95). All patients underwent manual palpation of the involved lung(s) during surgery. Palpation was unilateral in 20 and bilateral in 40. Operative approach was by means of sternotomy in 30 cases, unilateral thoracotomy in 19 cases, and substernal handport in 11 cases.

View larger version (18K): [in this window] [in a new window]   Fig 1. Primary tumor histologic diagnoses of the 53 study patients. (AML = acute myeloid leukemia.)

Additional analysis was done to determine whether the slice thickness was at all a factor in determining the accuracy of the helical scans. The results were stratified into four groups based on thickness: 9 were 4 mm, 9 were 5 mm, 39 (38 for radiologist 2) were 8 mm, and 2 were 10 mm. The sensitivities and PPVs for these groups can be seen in Table 4. There was no statistically significant improvement in sensitivity or decrease in PPV with smaller slice thicknesses.

	Comment

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In a previous retrospective study, we tested the hypothesis that helical CT was sufficiently sensitive to make palpation of the lungs unnecessary to resect all detectable metastases [9]. To our surprise, however, in 22% of patients, helical CT missed metastases that were detected by palpation. In addition, several other similar analyses were published that corroborated these results [10–13]. We considered what factors might have contributed to these results. We set out to try to discern whether there was an inherent error simply because the radiologists did not read the scans with the specific goal of identifying each suspicious lesion. Furthermore, we sought to explore whether the training and focus of the radiologist was a factor in the scan interpretation. Finally, we considered that using the gold standard of intraoperatively detected metastases inherently favored the surgeons’ assessment (through palpation), and that a better gold standard might be all metastases as demonstrated either by resection or by subsequent progression. A retrospective study was chosen because it allows the question to be explored more rapidly than a prospective study, although there are limitations to a retrospective analysis.

We found that despite a specific focus on identifying all pulmonary metastases, helical CT scan interpretation still missed metastases in almost 50% of the patients. Although both the sensitivity and the PPV were slightly improved when the gold standard included lesions missed by the surgeon and subsequently demonstrated to be metastases by interval growth, the sensitivity of CT was still not sufficient to avoid palpation. Furthermore, the PPV of the CT interpretation was still only approximately 60% to 70%. On the other hand, approximately one third of the lesions palpated and resected by the surgeon turned out to be benign [9]. Thus, neither the scan interpretation nor intraoperative palpation is completely accurate, and the two must continue to be used in a complementary fashion. The improved late sensitivity and late PPV resulting from the second analysis demonstrate that surgical palpation alone is not an absolute standard. This second analysis was not perfect, because there was no guarantee that a nodule seen to progress on follow-up was actually the specific nodule seen within the same lobe on preoperative CT and not found by the surgeon. Additionally, not all of the lesions that progressed were pathologically confirmed metastases, only highly suspicious lesions. Nevertheless, we believed that this analysis was valuable in comparing the radiologists’ results and the surgeons’ results in a way that was not inherently biased in favor of surgery. It added an objective measure of the accuracy of manual lung palpation. Of the metastases correctly called on preoperative CT (by the follow-up analysis), 34% (radiologist 1) and 26% (radiologist 2) could not be found by the surgeon at the time of initial exploration. These findings emphasize the importance of follow-up CT scanning, even if complete palpation of the lungs was performed.

Additionally, preoperative helical CT scanning is not sufficiently accurate to allow the surgeon to modify the surgical approach to include or exclude evaluation of both lungs. In our analysis this would have resulted in many missed contralateral lesions. This is further justification for a sternotomy or a subxiphoid approach allowing palpation of both lungs without thoracotomy whenever feasible.

To our surprise, the 54% sensitivity of helical CT scanning in this review was even lower than the 78% sensitivity resulting from our previous review. The sensitivity in our previous study was based purely on retrospective chart review, rather than chart review and re-review of the CT scan by two radiologists as in this study. It is unclear why this is the case, but given the increased number of patients in the current study, this may be a more accurate reflection of helical CT scan sensitivity. Additionally, the first study included the preoperative scan interpretation of both the thoracic surgeon involved with the case and the radiology report, which may have altered the accuracy of the interpretation. In the previous study, any suspected metastasis identified preoperatively on either the CT scan report or in the surgeon’s preoperative note was counted. We did not find any indication that the degree of specialization of the radiologist had any influence on the accuracy of helical CT scanning in identifying pulmonary metastases, but did not assess specifically the surgeon’s CT scan interpretation.

Both single and multislice CT imaging were used in this study. A prior study of autopsy lungs with histopathologic correlation demonstrated no difference in pulmonary nodule detection between single-slice and multislice CT when both were reconstructed using a 5-mm slice thickness [16]. However, in patients, multislice CT may result in improved nodule detection as a result of shorter breathhold requirements [17].

An argument can be made that detection and resection of all metastases in one operation might not be clinically important, as long as subsequently demonstrated metastases are removed later. The general experience with metastasectomy is that approximately two thirds of patients will experience recurrence, evidence that even surgical palpation misses metastases in the majority of patients [14]. The demonstration of subsequent metastases may be the most sensitive and specific method of identifying all metastases. Unfortunately, there are few data that can be called on to answer this question. An international randomized clinical trial (Cancer and Leukemia Group B 39804) to address this question was unable to accrue enough patients to yield any meaningful data and was closed prematurely. General experience has suggested that a second or third metastasectomy yields reasonably good survival, but these data stem from selected patients, who underwent lung palpation at the time of each resection [14]. A retrospective study that compared patients with radiographically unilateral disease who underwent sternotomy with those who underwent unilateral thoracotomy found no survival difference between the groups (again, in selected patients) [18]. Thus, although there are some retrospective data that can be extrapolated to suggest survival may not be affected, it is difficult to use this as a generalized argument that resection of all potentially detectable lesions is unnecessary, because these limited data involve selected patients who underwent palpation.

The key issue underlying whether it is important to perform as complete a metastasectomy as possible immediately versus a less-complete resection with subsequent reoperation is whether metastases left behind can beget further metastases. Data to address this question are scant, and there is no way to determine directly whether a pulmonary metastasis originated from the primary tumor site or developed subsequently from another pulmonary metastasis. In recent years, however, there has been an increasing recognition that regional lymph node involvement occurs in a relatively high percentage of patients with pulmonary metastases [19]. It seems much more likely that the adjacent lymph nodal involvement originates from the pulmonary metastasis, rather than direct seeding from the primary tumor site that just happened to involve both a site in the lung and the adjacent nodes. This provides a weak argument that pulmonary metastases can spread to other tissues, and therefore that removal of all metastases to the best of our ability is worthwhile. After all, the goal of metastasectomy is long-term cure, and there are no data to suggest that removal of only some metastases has any palliative benefit.

Technologic improvements may alter how detection of all pulmonary metastases is achieved in the future. The experience with CT imaging as a screening test for lung cancer has shown that the proportion of patients in whom small lesions are detected has jumped from 25% to 75% with multidetector scanners and thinner collimation. This underscores that an improvement in sensitivity may come at the cost of such a loss in specificity that it is problematic. However, advances in volumetric analysis or in computer automated detection programs may provide a dramatic improvement in specificity [17].

At the present time, pulmonary metastasectomy with curative intent should still involve palpation of both lungs. The data from this study demonstrate that modern imaging (as it was routinely available at the time of this study) is not sufficiently sensitive to detect all pulmonary metastases. The question of whether resection of all metastases at one time is critically important (versus careful follow-up and re-resection) remains unanswered This approach should only be used in the context of a prospective clinical trial with careful, prospectively planned follow-up imaging, and otherwise complete resection should remain the standard of care. Furthermore, although radiofrequency ablation of pulmonary metastases has yielded interesting preliminary response results, it should also be used only in the context of a clinical trial and in appropriately selected patients. Long-term survival data are lacking, and radiofrequency ablation relies on imaging alone, which this and other studies have demonstrated to be suboptimal. Both the low sensitivity and high false-positive rate of helical CT are particularly problematic if radiofrequency ablation is to be used as a potentially curative approach for pulmonary metastases. Therefore, we conclude that despite advances in surgery and imaging technology, intraoperative palpation and resection of all pulmonary lesions should remain the standard approach for pulmonary metastasectomy.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
We wish to acknowledge the assistance of Julius Atashili, MD, in the statistical analysis, and the editorial assistance of Margaret Alford Cloud in preparation of the manuscript.

	References

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Alden M. Parsons Frank C. Detterbeck Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Parsons, A. M. Articles by Detterbeck, F. C. Search for Related Content PubMed PubMed Citation Articles by Parsons, A. M. Articles by Detterbeck, F. C. Related Collections Lung - other Related Article