Accuracy of Helical CT in the Detection of Pulmonary Metastases: Is Intraoperative Palpation Still Necessary?

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1 Accuracy of Helical CT in the Detection of Pulmonary Metastases: Is Intraoperative Palpation Still Necessary? Alden M. Parsons, MD, Frank C. Detterbeck, MD, and Leonard A. Parker, MD Department of Surgery, Division of Cardiothoracic Surgery, and Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Background. Pulmonary metastasectomy is well accepted in patients with isolated metastases from an extrathoracic malignancy. The standard approach involves careful intraoperative palpation of the lungs because more metastases are frequently found than were seen by preoperative conventional computed tomography (CT). Helical CT detects more nodules than conventional CT, raising the question of whether palpation of the lungs is still necessary if helical CT is used. Methods. Retrospective review was done of medical records of patients undergoing metastasectomy with curative intent at the University of North Carolina (UNC) from 1999 to During this time at UNC, helical CT was routinely performed using a standardized technique, and all metastasectomy patients underwent manual lung palpation. The primary outcome measure of this study was whether malignant nodules (palpated, resected, and proven histologically) were reliably detected preoperatively by helical CT. Results. Thirty-four patients were identified who underwent 41 cases of pulmonary metastasectomy with lung palpation. Our analysis revealed that in 22% (9/41), more malignant nodules were found intraoperatively than were detected by helical CT. Of 88 malignant intraparenchymal nodules, 69 were detected by helical CT (sensitivity 78%). Subset analyses of tumor histology, disease-free interval, the presence of a single lesion versus multiple lesions, the interval between the CT and metastasectomy, and the size of the largest lesion were unable to identify a cohort in which lung palpation was no longer needed after preoperative helical CT. Conclusions. Despite the advent of helical CT, palpation of the lung is necessary if the goal is to resect all detectable disease. (Ann Thorac Surg 2004;78:1910 8) 2004 by The Society of Thoracic Surgeons Pulmonary metastasectomy has become a standard treatment for selected patients with isolated pulmonary metastases from extrathoracic primary malignancies. Much retrospective data substantiate a reasonable chance of long-term cure with this approach. This approach is believed to result in a distinct survival advantage relative to patients in whom pulmonary metastases are not resected [1 8], although randomized data addressing this aspect are not available. Furthermore, resection of pulmonary metastases can be accomplished safely, with perioperative mortality consistently 2% or less in large series [8 11]. The goal of pulmonary metastasectomy has been to render the patient disease-free. To achieve this goal, it is widely accepted that patients are candidates for pulmonary metastasectomy only if the primary tumor is controlled, the metastatic disease is confined to the chest, Accepted for publication May 17, Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26 28, Address reprint requests to Dr Detterbeck, Division of Cardiothoracic Surgery, Medical School Wing C, Room 354, CB #7065, University of North Carolina, Chapel Hill, NC ; fdetter@med. unc.edu. and a complete resection appears to be feasible [8 10, 12 15]. Careful and thorough manual palpation of the lungs has been the standard intraoperative approach to ensure that no pulmonary metastases remain after metastasectomy [8]. This strategy has been a result of the consistent detection of 30% more metastases by palpation than were recognized by traditional computed tomography (CT) scanning [8, 16, 17]. Furthermore, palpation is easily accomplished using the traditional surgical approaches of thoracotomy or sternotomy [18 20], which provide easy access for manual palpation. Medical progress has resulted in the widespread availability of helical CT scanners, in which thin-section imaging of the chest is carried out with a single breathhold. Experience has shown that helical CT detects approximately 20% more nodules than conventional CT [3, 21, 22]. This calls into question whether palpation of the lungs is still necessary at the time of metastasectomy. This issue is all the more important with the availability of minimally invasive video-assisted thoracic surgery (VATS) techniques that allow resection of pulmonary nodules through incisions 1 cm or less in length, but preclude lung palpation. Therefore, we sought to retrospectively assess whether lung palpation at the time of 2004 by The Society of Thoracic Surgeons /04/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg PARSONS ET AL 2004;78: HELICAL CT AND PALPATION DURING METASTASECTOMY metastasectomy was still of value if the preoperative evaluation consisted of a helical CT. Patients and Methods A retrospective review was performed of all patients undergoing pulmonary metastasectomy with curative intent at The University of North Carolina at Chapel Hill (UNC) from January 1999 to December Patients were considered candidates for metastasectomy with curative intent if the site of the primary tumor was controlled, no other sites of metastatic disease were present, and the pulmonary metastases were thought to be completely resectable. All surgical procedures were performed by 1 of 3 faculty thoracic surgeons at UNC. The standard approach to metastasectomy at UNC during this time was intraoperative manual palpation of the lungs and resection of all palpable lesions. To be included in the study, patients had to have undergone a preoperative helical chest CT scan. During this time, chest CT scans at UNC were done according to a standard protocol using a spiralacquisition single-breath-hold technique. Of the 41 total chest CT scans, 35 studies were performed on a singledetector scanner (Siemens Somatom Plus 4, Iselin, NJ) with 8-mm slice collimation, pitch of 1:1, and 8-mm reconstruction for slice thickness and table increments. One study was performed on this scanner with 5-mm acquisition, pitch of 1:1, and 5-mm reconstruction. Five scans were performed on a multidetector scanner (Siemens Somatom Sensation, Iselin, NJ) with 1.5-mm detector collimation and 5-mm reconstruction. Scans were routinely performed while infusing intravenous contrast (Iohexol 300, Amersham Health, Cork, Ireland) at a rate of 1.5 to 2.0 ml/s. All studies were reviewed with both lung and mediastinal windows. Preoperative clinic visit notes, preoperative chest CT scan dictations, operative reports, and pathology reports for each procedure were reviewed. Recorded data included the number and location of nodules suspected preoperatively; the number and locations of nodules palpated intraoperatively; and the number, location, and size of nodules that were confirmed to be malignant metastases on pathologic evaluation. All nodules were recorded that were identified preoperatively on either the CT scan report or in the surgeon s preoperative note. These numbers were compared with the number of pathologically proven metastases as the primary outcome measure. The CT-detected nodules and the intraoperatively detected nodules were compared in each case on a lesion-by-lesion basis to determine exactly which nodules were seen, palpated, and resected. Because the outcome of most concern is the ability to detect malignant nodules, the primary comparison was whether malignant nodules that were found intraoperatively and proven histologically were detected preoperatively by helical CT. Whether nodules that were benign were detected by helical CT was considered to have limited clinical relevance. Thus, the sensitivity of helical CT was calculated by the number of actual malignant nodules that were seen on the preoperative CT, divided by the total number of malignant nodules found intraoperatively. On a per-patient basis, the sensitivity of helical CT was calculated as the number of patients in whom all malignant nodules were seen preoperatively divided by the total number of patients. The determination of how a lesion was counted was made individually for each lesion, based on the location as noted on the CT and by the intraoperative findings. Seven nodules were seen preoperatively that could not be found by intraoperative palpation. In each of these cases, the surgeon searched specifically for the lesion and could find no abnormality. These nodules were counted as benign. The size of these lesions ranged from 5 to 33 mm (5, 7, 9, 10, 10, 33 mm); data on size were missing from the CT reports for one of these nodules. The false-positive rate of helical CT was calculated as the number of nodules seen preoperatively that were benign divided by the total number of nodules seen (which were all suspected to be malignant). Calculations were based on all patients thought preoperatively to have isolated pulmonary metastases in whom metastasectomy with curative intent was planned, instead of only those patients in whom actual metastases were found. This was done in order to present data applicable prospectively to other patients. In effect, however, the nodules in patients who had only benign disease did not enter into the calculations of the sensitivity of helical CT. The nodules of patients who were found on final analysis to have new primary lung cancers did enter into the calculation of sensitivity of helical CT. This approach seems appropriate because these lesions would be of serious consequence if missed. All subset analyses were done on a per-nodule basis, as this strategy resulted in greater precision and served the purpose of an exploratory analysis to see if a unique subgroup could be identified. For all analyses, a p value of 0.05 was considered to be significant. For the single versus multiple nodule subset analysis, Fisher s exact test was used. For the histologic and maximum nodule size subset analyses, a 2 test was used. For the length of CT OR interval subset analysis, the Mantel-Haenszel 2 value (or mean score statistic) test was used. Ninety-five percent confidence intervals were calculated for all proportions. Results 1911 From 1999 to 2003, 34 patients who met the study criteria underwent 41 procedures for pulmonary metastasectomy at UNC. Five patients underwent more than one pulmonary metastasectomy for recurrence. During this period, 2 additional patients underwent metastasectomy with curative intent, but were excluded because their preoperative CT scans had been done elsewhere. In several additional patients during this period, a planned metastasectomy was aborted when it became apparent that a complete resection could not be accomplished (this observation was usually noted intraoperatively). However, GENERAL THORACIC

3 1912 PARSONS ET AL Ann Thorac Surg HELICAL CT AND PALPATION DURING METASTASECTOMY 2004;78: Fig 1. Distribution of primary tumors. (H&N head and neck.) Fig 2. (A) Sensitivity of helical computed tomography (CT) in 41 cases. (B) Sensitivity of helical CT for 88 malignant nodules. the exact number of these cases could not be determined in this retrospective review. The average age of patients undergoing pulmonary metastasectomy was 50 years (median 53, range 15 to 81 years). There were 20 men and 14 women. The distribution of primary tumor types is provided in Figure 1. The most common primary tumor histology was sarcoma, of which 47% (8/17) were osteosarcoma. There were 14 cases in which only one nodule was seen preoperatively, 10 cases with two nodules, 6 with three, 4 with four, 4 with five, and 3 with six or more nodules seen preoperatively. Disease-free interval for the entire patient group averaged 27.5 months (range 0 to 219 months, median 13 months). The disease-free interval was less than 12 months in 14 cases, 12 to 24 months in 8 cases, 24 to 36 months in 5 cases, and greater than 36 months in 9 cases. The helical CT scans were obtained an average of 33 days before the metastasectomy (range 1 to 95 days, median 30 days). In patients in whom the scan was obtained more than 45 days before the metastasectomy, the delay was because of difficulties in scheduling the operative procedure in five cases, waiting to obtain additional studies (positron emission tomography, magnetic resonance imaging, CT abdomen/pelvis) in 3 patients, interval surgical resection of the primary tumor in 1 patient, and for an unclear reason in 1 patient. Because of the variation in the interval from the CT to the metastasectomy, the data were analyzed separately for cases with an interval of less than 30 days, 30 to 45 days, and greater than 45 days. All patients underwent manual palpation of the involved lung (n 11) or both lungs (n 30). Palpation was accomplished through sternotomy (n 19), unilateral thoracotomy (n 11), or by VATS with a substernal handport (n 11) for palpation as described elsewhere [23, 24]. Two of the cases involving unilateral palpation were staged thoracotomies on a single patient. One case involved the discovery of a new primary lung cancer rather than metastatic disease, and therefore contralateral palpation was no longer considered. One case required a thoracotomy for chest wall and diaphragmatic resection along with the metastasis. In the remaining 7 patients who underwent only unilateral lung palpation, the location of nodules seen required resection through a thoracotomy and there was a low clinical suspicion of additional metastases. An exception to the standard UNC approach of bilateral lung palpation was made to avoid making a contralateral thoracotomy. In the 41 cases a total of 134 nodules were palpated and resected. A focus of malignancy was found in 88 of these nodules and in 38 of the 41 cases. In three cases only a benign process was identified (a cryptococcal infection, a granuloma, and a meningothelioid nodule in 1 patient each). Nonmetastatic malignant nodules were found in 2 of the 41 cases (two primary non small cell lung cancers). Thus 34% (46 of 134) of the nodules palpated intraoperatively turned out to be benign. Preoperative helical CT detected 97 nodules, of which 71% (69/97) turned out to be malignant. Therefore, the false-positive rate of nodules seen on CT was 29% (28/97; (95% confidence interval [CI], 0.20 to 0.38). Overall, helical CT detected 97 of the 134 (72.4%) nodules (95% CI, 0.65 to 0.80) palpated intraoperatively. Seven nodules seen on preoperative CT could not be palpated intraoperatively, despite careful searching intraoperatively for each specific lesion seen on the CT scan. On a per-case basis, benign lesions were found in 37% (15/41) of cases in whom malignant nodules were suspected by helical CT scan. Overall, helical CT predicted the correct number of malignant nodules in 17/41, or 41% (95% CI, 0.26 to 0.56) of cases; predicted more lesions (false positives) in

4 Ann Thorac Surg PARSONS ET AL 2004;78: HELICAL CT AND PALPATION DURING METASTASECTOMY Table 1. Details of Missed Metastatic Lesions Case No. No. of Missed Metastatic Lesions Size of Missed Metastatic Lesions (mm) CT OR Interval (days) 1913 Reason for CT Misinterpretation GENERAL THORACIC Central location Atelectasis Unknown Unknown Confluence of vessels Atelectasis Unknown Unknown 41 1 Unknown 13 Diaphragmatic surface CT computed tomography scan; OR operative resection. 15/41, or 37% (95% CI, 0.22 to 0.52); and less than the true number of malignant lesions (false negatives) in 9/41, or 22% (95% CI, 0.09 to 0.35) (Fig 2A). Helical CT identified only 69 of the 88 malignant nodules, for a per-nodule sensitivity of 78% (95% CI, 0.69 to 0.87) (Fig 2B). Excluding cases in which the nodules were benign or a new primary lung cancer, helical CT identified 67/86, or 78% (95% CI, 0.69 to 0.87) of the nodules that were pulmonary metastases. On a per-case basis, helical CT identified all malignant nodules in 32/41, or 78% of cases (95% CI, 0.65 to 0.91), and failed to detect all malignant nodules in 9/41, or 22% (95% CI, 0.09 to 0.35) of cases (Fig 2A). The 19 malignant nodules not detected by helical CT are summarized in Table 1. All of the missed nodules were 10 mm or less in diameter. Table 2. Helical CT Sensitivity of Patient Subsets Helical CT Sensitivity (%) p 95% Confidence Intervals Length of CT-OR interval 30 days 73 NS days days Tumor histology Sarcoma 75 NS Nonsarcoma Size of largest nodule 2 cm 66 NS cm Multiple nodules versus single Single Multiple Disease-free interval 2 yrs 67 NS yrs CT computed tomography scan; NS not significant; OR operative resection. Some of the lesions were misinterpreted as foci of atelectasis or a confluence of vessels. The interval between the CT and the metastasectomy did not account for the low overall sensitivity of helical CT (Table 2). The (per-nodule) sensitivity of helical CT was 73%, 83%, and 86% for cases in which the interval from CT to metastasectomy was less than 30 days, 30 to 45 days, and greater than 45 days, respectively (p not significant [NS]). The (per-nodule) sensitivity of CT was better in cases in which multiple nodules were seen preoperatively (sensitivity 85% for multiple nodules, 55% for a solitary nodule, p ). Whether the primary tumor was a sarcoma or another cancer type did not define a subgroup in which helical CT was sufficiently sensitive to avoid palpation (per nodule sensitivity 75% in cases of sarcoma and 85% in nonsarcoma cancers, p NS). The disease-free interval also did not allow definition of a group of patients in whom the preoperative helical CT was reliable. The (per-nodule) sensitivity of helical CT was 80% for patients with a disease-free interval of more than 2 years and 67% for patients with a disease-free interval of 2 years or less (p NS). Comment Metastasectomy has become well accepted as a curative treatment strategy in patients with isolated pulmonary metastases from extrathoracic primary malignancies [1 15]. The standard approach is to palpate the lungs at the time of resection in order to not leave any metastases behind [8, 25]. Although the mortality of a conventional metastasectomy via sternotomy or thoracotomy is low ( 2%) [8 11], it is tempting to consider approaches with less morbidity. Video-assisted thoracic surgery is minimally invasive, but does not permit palpation of the lungs. Controversy persists about whether this technique is appropriate for patients undergoing metastasectomy with curative intent [26 28]. Some centers have adopted a VATS approach routinely and reported encouraging survival rates. For example, Landreneau and colleagues [26] reported a 5-year survival rate of 30.8% in 80 patients undergoing VATS

5 1914 PARSONS ET AL Ann Thorac Surg HELICAL CT AND PALPATION DURING METASTASECTOMY 2004;78: pulmonary metastasectomy for colorectal primaries. However, these results cannot be compared easily with series of patients undergoing conventional metastasectomy, because of the multitude of variables involved such as histologic cancer type, disease-free interval, and other selection factors. Whether there is any difference in survival after metastasectomy with versus without manual lung palpation can only be assessed by a randomized study. As a surrogate for long-term survival, we sought to retrospectively investigate whether palpation of the lungs was still necessary given modern imaging techniques, because the inability to palpate the lungs is the most obvious limitation of the purely thoracoscopic approach. The standard dictum that palpation is necessary is borne out of the historical experience that palpation identifies approximately 30% more lesions than are seen on a conventional (nonhelical) CT scan [8, 16, 17]. Helical CT has been shown to detect approximately 20% to 25% more nodules than conventional CT [3, 21, 22]. Therefore, it is possible that modern imaging techniques may make palpation of the lungs obsolete. During the period of this study, helical acquisition CT scans were standard at UNC. The technique of scanning and image reconstruction was relatively uniform. Palpation of the lungs was also standard at UNC. Thus, we thought a retrospective review of the value of palpation compared with the results of preoperative helical CT results would be useful. Our results demonstrate that helical CT is not sensitive enough to obviate the need for lung palpation if resection of all detectable metastases is the goal. Approximately 22% (9 of 41) of patients would have detectable malignant nodules remaining if helical CT alone were used to guide resection, despite the increased sensitivity of helical CT over conventional CT imaging. Although helical CT may be an advance over conventional CT, it is not reliable enough as used in actual clinical practice to omit intraoperative palpation of the lungs. We sought to identify a subgroup of patients in whom helical CT would have greater sensitivity, but such a cohort could not be identified. The sensitivity of helical CT for detection of malignant nodules remained too poor to rely on as a sole modality regardless of the underlying type of malignancy, the interval between the CT and metastasectomy, the disease-free interval, the number of lesions present, or the size of the largest lesion. Although small differences in sensitivity may have been missed because of the limited number of patients in each subgroup, it does not appear likely that a subgroup of patients exists in which helical CT is sufficiently reliable to avoid palpation. An argument can be made to exclude cases that were identified after resection as not having metastatic disease (those with either benign nodules or new primary cancers). However, exclusion of such cases makes the data less prospectively applicable to a prospective preoperative patient. Furthermore, when we recalculated the sensitivity of CT after excluding such cases, no appreciable difference was noted. The sensitivity of helical CT was also 78% in only those patients with metastases. Table 3. Reports of Helical CT Sensitivity in Detecting Pulmonary Metastases Study N No. of Helical CT Metastases Sensitivity (%) Waters et al 1998 [31] 4 (dogs) Diederich et al 1999 [30] Ambrogi et al 2000 [24] Margaritora et al 2002 [29] Current study Other studies of helical CT have found remarkably similar results to our study. The sensitivity of helical CT for the detection of histologically proven pulmonary metastases ranges from 56% to 84% among small retrospective studies addressing this issue (Table 3) [24, 29 31]. Not surprisingly, helical CT was most likely to miss small nodules ( 6 mm in diameter). Thus, our experience is consistent with the experience with helical CT at other centers around the world. Technological improvements in CT scanners continue to be made. During the time of this study, the latest technology helical CT scanners were used, with acquired images at 8-mm intervals, with 8-mm reconstructions. A few patients at the end of the study underwent helical CT scans with newer-generation scanners 1 patient had a scan with 5-mm collimation and 5 patients had scans performed on a multidetector scanner. Decreasing the collimation will increase spatial resolution in the z-axis, with a trade-off of increased radiation exposure and longer scan time during a breath-hold. The protocol used was based on a prospective selection of the parameters chosen as the best compromise. At any rate, in a retrospective study, what has been done cannot be changed. However, it should be noted that a pitch of 1:1 results in all portions of the lung being examined by the incident radiation, and does not require interpolation of data for regions of lung that have not been scanned. A pitch of less than 1:1 results in portions of lung that are overirradiated. An additional limitation of helical CT may be a failure of the image interpretation rather than the imaging technique itself. In reality, a judgment is always made regarding which lesions appear suspicious. The printed interpretation by the radiologist of helical CT in these patients may have failed to mention additional smaller nodules because they were not considered to be important. Indeed, most of the missed nodules were less than 8 mm. Therefore, we recorded any nodule noted preoperatively, either by the radiologist or the surgeon. It was customary at UNC for the surgeon to clearly describe the location and number of the suspicious nodules seen. Furthermore, we surmised that the radiologist and the surgeon may have been less diligent in mentioning each nodule if several lesions were seen. Therefore, we were particularly interested in whether the sensitivity of helical CT was higher among patients in whom only one lesion was seen. This was not the case; in fact, the

6 Ann Thorac Surg PARSONS ET AL 2004;78: HELICAL CT AND PALPATION DURING METASTASECTOMY sensitivity of helical CT was significantly better when multiple lesions were present. However, the sensitivity in the case of multiple lesions was still not high enough to obviate the need for palpation. We plan to retrospectively review the CT images in a controlled fashion to study the possible factors related to scan interpretation that may have accounted for the low sensitivity. Although it is possible that retrospective review of the CT scans after resection might identify more lesions than were noted preoperatively, the results of our study represent the actual clinical experience in a center with an interest in metastasectomy and defined policies regarding the management of these patients. The experience with CT as a screening tool for lung cancer has revealed that small nodules a few millimeters in size are detected in a large proportion of patients. The problem with CT screening for new primary lung cancer has been that the sensitivity is too high, resulting in detection of a large number of benign (false-positive) nodules. However, this experience may not apply to suspected pulmonary metastases. Certainly the prevalence of metastases in patients with a history of a prior extrathoracic malignancy is higher than the prevalence of new primary lung cancers in a healthy population. Furthermore, many of the patients with a prior malignancy have had a baseline CT scan. Nevertheless, it is unclear why the sensitivity of helical CT in our experience and in other studies has been too low, whereas the sensitivity is too high when screening healthy patients for primary lung cancer. In our series, seven nodules seen on preoperative helical CT were not found by intraoperative palpation. This occurred despite careful, directed palpation based specifically on the CT findings. Three of these nodules were in a single patient, who died on postoperative day 3 of a bleeding ulcer after refusing a blood transfusion, and hence has no follow-up. Two of the missing nodules were in a patient with a new primary lung cancer diagnosed at the time of intended metastasectomy, who has had no recurrence as of last follow-up at 47 months after the operation. The other two single missing nodules were in patients who were disease free at 5 months and 25 months after the operation. Thus it appears that the missing nodules were radiographic changes that had resolved by the time of resection. This assumption is corroborated by the experience with CT screening for lung cancer [32]. Specific radiographic characteristics that correlated with a disappearing lesion could not be identified from the CT reports. If the underlying premise is accepted that the best strategy is to resect all detectable malignant lesions at the time of the operation, then palpation of the lungs is still necessary. However, some researchers have proposed that equal results might be achieved if only radiographically visible lesions were resected, provided lesions that are found on subsequent scans are subsequently also resected [33]. The patients who will benefit from metastasectomy are those that have oligometastatic disease. If these metastases can be removed in several minimally invasive operations, equal survival might be achieved, provided the risk of further metastatic spread from a remaining pulmonary focus of cancer is low. This hypothesis has been suggested in several previous retrospective reports [34, 35]. Currently, however, no prospective randomized data exist to substantiate or refute this speculation. In 1999 the Cancer and Leukemia Group B (CALGB) initiated an international randomized trial to address this question (CALGB 39804). Unfortunately, the trial was closed due to inability to meet the accrual goal. Palpation of the lungs results in the detection of more metastases than are detected by helical CT. Thus, we conclude that palpation of the lungs should remain the standard approach. Novel techniques such as a substernal handport, as we and others have reported elsewhere [23, 24], provide a less invasive alternative to sternotomy or thoracotomy yet still allow lung palpation. Perhaps new insights into markers of the biological behavior of tumor cells will lead to a better prediction of oligometastatic disease that would make it worthwhile to revisit whether helical CT is good enough to obviate the need for lung palpation in certain subgroups of patients with isolated pulmonary metastases. Perhaps multidetector CT imaging will have adequate sensitivity to avoid the need for palpation. However, at this time, palpation of the lungs at the time of metastasectomy continues to be necessary. The authors thank Bonnie C. Yankaskas, PhD, Professor of Radiology and Adjunct Professor of Epidemiology at the University of North Carolina at Chapel Hill, for her review of the data and statistical analysis. References Tafra L, Dale PS, Wanek LA, Ramming KP, Morton DL. Resection and adjuvant immunotherapy for melanoma metastatic to the lung and thorax. J Thorac Cardiovasc Surg 1995;110: Carter SR, Grimer RJ, Sneath RS, Matthews HR. Results of thoracotomy in osteogenic sarcoma with pulmonary metastases. Thorax 1991;46: Jablons D, Steinberg SM, Roth J, Pittaluga S, Rosenberg SA, Pass HI. Metastasectomy for soft tissue sarcoma. Further evidence for efficacy and prognostic indicators. 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Pulmonary metastases: biologic and historical justification for VATS. Video assisted thoracic surgery. Eur J Cardiothorac Surg 1999;16(Suppl 1):S Rizzoni WE, Pass HI, Wesley MN, Rosenberg SA, Roth JA. Resection of recurrent pulmonary metastases in patients with soft-tissue sarcomas. Arch Surg 1986;121: Kandioler D, Kromer E, Tuchler H, et al. Long-term results after repeated surgical removal of pulmonary metastases. Ann Thorac Surg 1998;65: DISCUSSION DR NASSER K. ALTORKI (New York, NY): I want to congratulate you. This is a timely piece of work. We were actually discussing this the other day. Since the old CT series that showed that 50% are not found until the time of thoracotomy, there has been nothing so detailed as the work that you have just presented. I think the problem with any such work is that the technology so far outpaces what we do. Now we are looking at 5-mm collimations and 1-mm collimations and a volume CT that is in prototype that will soon be released. And the question is, are we going to always be playing catch-up at a time when patients and the referring physicians are looking for minimally invasive procedures? The other point I would like to make is that lesion detection accuracy is not only a function of the collimation but also a function of the person reading the scan. I do not know if your institution is like ours, but I will get a report that says numerous bilateral nodules, and then I have to go and sit the radiologist down and we go ahead and circle every single lesion before we make a determination about what we are going to do. I was wondering if you went back and looked at those 20% missed lesions. Were they in fact present and just simply missed by the reader or were they missed as a function of the quality of the scan? I really enjoyed your presentation. I think it is an important contribution. DR PARSONS: Thank you. With regard to the CT collimation, that is something we have discussed with our radiologists at UNC, and that is an important point. It is clearly a factor in the CT scan sensitivity, but it is difficult to evaluate retrospectively. In our data set, all but six scans were done with 8-mm collimation. With regard to whether the nodules were there in retrospect, it was customary at UNC for the surgeon to actually review the scan and dictate in clinic notes where the lesions were, and most of the time lesion location was in the indications in the operative note as well. But that is a good point. We are conducting a follow-up study with our radiologists in which they reread all the scans to more definitively evaluate whether the missed lesions could have been detected preoperatively.

8 Ann Thorac Surg PARSONS ET AL 2004;78: HELICAL CT AND PALPATION DURING METASTASECTOMY DR JOSEPH B. SHRAGER (Philadelphia, PA): My first question is similar to Nasser s. Was the reading standardized by an outside radiologist, a UNC radiologist, or the surgeon, or was it variable? DR PARSONS: It was both. We had preoperative clinic visit dictation notes and the radiologist s dictation from UNC, and in one case we had an outside read. However, in all the cases we took the total number of lesions that were found by either the surgeon or the radiologist. DR SHRAGER: So the maximum number was used? I think that point is important in interpreting your data. DR PARSONS: The maximum number, yes. DR SHRAGER: I remember when Pat McCormack presented a similar study several years ago reporting on the oldergeneration CT scans, the findings created sort of an uproar. I will ask a question that was asked then, which is: Are you proposing that we should do sternotomies so that both sides can be palpated even if there is only a single unilateral lesion identified on CT? DR PARSONS: At UNC, palpation of both lungs is the standard approach, even if there is only a solitary unilateral metastasis. However, as I pointed out, we have started doing the cases through a substernal handport that allows bilateral palpation. I have limited experience with that technique myself, but the procedure enables bilateral manual palpation without a sternotomy. DR PARSONS: They were all 10 mm or less DR MILLER: That is an important question, because if you have an individual who has a single nodule in the right lung, and he is 3 or 4 years out from his primary, is it going to make that big of a difference if you miss that nodule? Because, then, you know, 2 or 3 years later you might want to remove it again thoracoscopically, where before, 6 or 7 years ago, we opened up everybody and palpated and so forth. But I like your technique with the VATS palpation. I have not done that before. But the big question is, in the time of their disease, with these small nodules that we are not finding, how is that going to change things? DR PARSONS: That is a larger question. I think some subsets of patients have missed lesions at the time of initial metastasectomy that are detected at follow-up. These patients are reresected and the survival is the same. Then some patients with more aggressive tumor biology do poorly after incomplete resections. The problem is that discriminating between those groups of patients preoperatively is often difficult. DR MILLER: Frank, I think for the American College of Surgeons Oncology Group, this would be a tremendous study to look at VATS-assisted palpation and things like that. DR HIRAN C. FERNANDO (Pittsburgh, PA): You mentioned that no difference was noted between the patients who had a single nodule and the patients with multiple nodules. How many patients in your study had a single nodule, and what percentage of those patients who had a single nodule were found to have a second nodule at the time of surgery? GENERAL THORACIC DR RAJA FLORES (New York, NY): You actually touched on one of the questions that I was going to ask. Can you describe this VATS substernal palpation? Is it a different procedure from the usual thoracoscopic digital palpation? Also, if you take into account that you are probably going to miss some nodules with this approach compared with an open thoracotomy, you may in fact actually have a higher incidence of cancer nodules missed by both CT and VATS. I believe your data showed 11 patients underwent VATS substernal palpation, so that is not an insignificant number. Would it be safe to say that your data probably underestimated the number of missed malignant nodules? DR PARSONS: Those procedures did actually have manual palpation. Use of the substernal handport, and actually Dr. Detterbeck might describe the procedure a little better than I can, involves a small epigastric incision with an extraperitoneal approach into the substernal space and into both the right and left chests. Both lungs can be completely manually palpated, so it is not a digital palpation. He felt comfortable that those lungs did not have further lesions. DR DETTERBECK: I think Dr Parsons stated it very well. With a substernal handport you can get your whole hand in all the way to the apex of the chest. You can palpate both lungs completely between the thumb and fingers of your hand. I think there is no difference from open palpation. We actually have analyzed the results of this approach separately for another publication. That abstract did not make the program for this meeting, however. DR DANIEL L. MILLER (Atlanta, GA): What was the average size of the nodules that were missed? Were they extremely small? DR PARSONS: We found a significant difference in terms of sensitivity. The scans in patients who had multiple nodules did end up being more sensitive than the scans in patients who only had a solitary nodule. DR FERNANDO: So how many patients in your group had just a solitary nodule and how many of that group had a second nodule that was found at the time of surgery? DR PARSONS: I think 11 patients had only a solitary nodule. The sensitivity of CT was 55% in patients in whom only a single nodule was seen preoperatively, and 85% when multiple lesions were seen. That finding did not necessarily make sense to us. We actually expected the converse. It may be that radiologists pay better attention to how many lesions there actually are when they see multiple nodules. That would be one way to explain it. DR JOSEPH I. MILLER (Atlanta, GA): I have two questions for you. Did you try to separate out the missed nodules by histology? We know that with sarcoma, 15%, 18%, or more are going to be found through past studies, whereas, at least in our own experience with renal, colon, and melanoma, the CT is pretty accurate and they are rarely missed. Did you separate out by histology? The second thing I would like to ask you, particularly with regard to your manual palpation through the VATS approach, Valerie Rusch about 3 to 4 years ago presented their study from Memorial about thoracoscopic resection, then opening the patients and finding a number of lesions missed by VATS. I dare say that maybe in sarcoma you will not miss many, but I wonder how you are going to be able to get at the deep nodules within the pulmonary parenchyma through the VATS approach. Maybe they should be done open.

9 1918 PARSONS ET AL Ann Thorac Surg HELICAL CT AND PALPATION DURING METASTASECTOMY 2004;78: DR PARSONS: We agree with you that they should be done open that is, with an approach that allows for palpation of the lung between the thumb and fingers of the whole hand. In terms of the histology, we did look at sarcoma versus nonsarcoma and we do not have adequate power to demonstrate any differences between those two, but we did not find a difference in sensitivity of scans that were in sarcoma patients versus nonsarcoma patients. DR NICHOLAS J. DEMOS (Jersey City, NJ): Speaking of missed nodules, even though the CT scan seems to be not very accurate in localizing things for the surgeon, I have had smaller nodules that I had to excise thoracoscopically. For a few of them, I was lucky I found them, but a few I could not even palpate. So lately I have enlisted the help of the radiologists and I have done needle localization, which has worked nicely. I was wondering if you could comment on that. DR PARSONS: We did have eight nodules that were seen on CT before the operation in which they were not able to be palpated in the OR. I think that radiographic localization may be a way to reduce that number, but I do not know that I can really comment further on that. However, at least some of the nodules seen but not felt may have been focal atelectasis or inflammatory lesions that cleared by the time of surgery. New Location for The Annals of Thoracic Surgery Editorial Office The Editorial Office of The Annals of Thoracic Surgery has moved. As of June 18, 2004, our new address is: The Annals of Thoracic Surgery Editorial Office 3440 Market St Suite 306 Philadelphia, PA by The Society of Thoracic Surgeons Ann Thorac Surg 2004;78: /04/$30.00 Published by Elsevier Inc