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Ann Thorac Surg 2004;78:1031-1036
© 2004 The Society of Thoracic Surgeons


Original article: general thoracic

Thoracoscopy using a substernal handport for palpation

Frank C. Detterbeck, MDa,*, Thomas M. Egan, MDa

a Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Accepted for publication April 1, 2004.

* 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 27599-7065, USA
fdetter{at}med.unc.edu


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
BACKGROUND: A substernal handport allows palpation of the lung and thus circumvents one of the major limitations of thoracoscopy.

METHODS: This approach has been used in 24 consecutive patients, primarily during planned metastasectomy or when palpation was needed for deeper or smaller lesions that were difficult to find.

RESULTS: No long-term complications from this procedure were noted, and the 3 early complications were either minor or unrelated to the procedure. This approach allowed adequate resection to be accomplished by a less invasive approach in 67% of patients, although conversion to an open procedure was necessary in 33% of patients for anatomic and technical reasons. Among the 16 patients who underwent this procedure alone, the median length of stay in the hospital was 3 days. The rate of incomplete resection and of recurrence after metastasectomy was comparable to that for an open approach.

CONCLUSIONS: Our experience documents that a substernal handport is safe, does not compromise the ability to perform an adequate metastasectomy, and allows biopsy of lesions that are otherwise not amenable to a minimally invasive approach. This technique should be included in the standard armamentarium of approaches for thoracic surgery.


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Thoracoscopy has become a standard technique for many thoracic surgical procedures. Technologic advances in instrumentation have aided greatly in the versatility of this technique. The major limitation of thoracoscopy is the inability to palpate structures. This is perhaps most evident when the surgeon is trying to find small nodules that are not directly on the surface of the lung. The inability to palpate the lung also raises concerns about the applicability of thoracoscopy to metastasectomy of extrathoracic primary cancers, because careful palpation of the lung is considered the standard approach in most centers to identify and resect all metastases.

We have adopted an approach that uses a substernal handport to allow manual palpation of the lung; this has been called hand-assisted thoracoscopic surgery (HATS) [1]. The technique is simple and is easy to perform. It has become standard in our practice for procedures in which manual palpation is needed, such as for metastasectomy or wedge resection of nodules that are difficult to locate. A similar technique has been previously described by others [2].

This report details our experience with this procedure. Patients were selected for the HATS approach if they were to undergo metastasectomy (because palpation of the lung between the fingers is considered standard) or if thoracoscopic biopsy without palpation (with or without computed tomographic [CT] localization) was anticipated to be difficult (because the lesion was small or deep or both). We sought to determine how often the HATS approach was successful in avoiding thoracotomy or sternotomy. We also wanted to determine the incidence of short-term and long-term complications. In addition, we wanted to assess whether there was any evidence that this procedure resulted in a higher rate of incomplete resections or recurrences compared with an open procedure in patients undergoing metastasectomy. Finally, we sought to assess whether palpation of the lungs identified additional metastases given the advances in CT scanning technology.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Operative technique
If bilateral handport access for palpation is required, such as for metastasectomy, the patient is positioned supine with the arms abducted on an arm board. We raise the forearms on a wedge to decrease tension on the muscles and brachial nerves during abduction, while keeping the elbows at the level of the table. The patient is prepped from the base of the neck to below the umbilicus (to allow a sternotomy if needed) and laterally to the edges of the table. When only a unilateral approach is needed, such as for location of small nodules, the patient is placed in a lateral decubitus position, but the sterile prep is extended across the midline from the midsternum to below the umbilicus. It is helpful to mark the skin in the midline before turning the patient, because the midline can become difficult to identify.

We generally begin with an initial visual inspection of the thoracic cavity with a 5-mm 30-degree thoracoscope. A midline epigastric incision is started at the lower portion of the sternum, just above the sternoxiphoid junction, and extended caudally for 8 to 10 cm. The linea alba is divided, but the peritoneum is left intact. The fascial attachments to the xiphoid are divided, and the xiphoid is generally removed. This not only allows better access, but also detaches the diaphragmatic attachments from the undersurface of the sternum and xiphoid. This provides an opening into the substernal space, which is enlarged with digital probing to allow access of the entire hand. Blunt dissection is then conducted into either the right or left pleural cavity (Fig 1).



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Fig 1. A hand is inserted through the linea alba and the substernal space into the pleural cavity.

 
A hand can then easily be inserted to allow palpation of even the apex of the chest (Fig 2). All lesions have been easy to locate when the deflated lung is palpated between the fingers, with no difference between any of the lobes. In approximately 30% of patients, palpation of the left chest can result in hypotension from compression of the right ventricle. This can generally be avoided by rolling the patient to the right side or by lifting the rib cage with one's wrist during palpation so that the heart is not compressed. Palpation of the right chest has not caused hypotension in our experience. We have not encountered bleeding from vessels in the substernal space as a result of the blunt dissection.



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Fig 2. The substernal handport allows palpation of the apex of the chest.

 
After a complete manual evaluation, wedge resection is performed. Sometimes it is easier to place the endoscopic stapler while a hand is in the chest to manipulate the lung and to assess the margin between the nodule and the staple line. The stapler can be placed through a port or through the epigastric substernal space. The substernal approach also facilitates removal of large specimens, such as when performing a thoracoscopic lobectomy for a large tumor. This avoids the need for rib spreading for specimen removal. Closure of the incision is achieved by reapproximating the linea alba and skin. We have not reattached the diaphragm in any of these cases.

Patient population
The records of all patients who underwent a HATS procedure at the University of North Carolina were reviewed; no patient was excluded. This included review of clinic records, reports of the preoperative CT scan, operative notes, discharge summaries, pathology reports, and all follow-up records, including chest radiograph reports and, if available, chest CT reports. Particular attention was paid to identification of any early or late complications or morbidity as a result of this procedure. Attention was also paid to the number of nodules identified relative to what was seen on the preoperative CT scan, as well as the completeness of resection and the rate of recurrence.

From January 2001 through the end of March 2003, 24 patients underwent a HATS procedure. Patients were selected for the HATS approach if they were to undergo metastasectomy (because manual palpation of the lungs is standard) or if they were to undergo wedge biopsy of a lesion that was believed not to be amenable to a thoracoscopic approach alone. During this time period, 10 additional patients underwent metastasectomy with a planned sternotomy or an open thoracotomy. In addition, 70 patients underwent a thoracoscopic biopsy without manual palpation for pulmonary lesions that could be localized and resected by standard thoracoscopic techniques, including insertion of a finger through a port site.

The HATS was a planned procedure in all but 2 patients, in whom a lesion could not be identified with thoracoscopy alone (despite preoperative CT-guided methylene blue localization in 1 of these). The lesions were easily identified with manual palpation and successfully resected in these patients. In 2 of the patients who underwent biopsy only, it was suspected that the lesion would not be able to be identified by using thoracoscopy alone without palpation, and a HATS approach did turn out to be necessary. In 3 patients, a HATS procedure was planned to assist in biopsy of lesions that were thought (correctly) not to be amenable to an approach with thoracoscopy alone. In one of these patients, a biopsy was obtained with a core needle using the handport to guide needle placement. In the other 2 patients, the lesions were either too large or too close to the hilum for safe removal with thoracoscopy alone. Finally, in 1 patient with limited pulmonary reserve, a HATS approach was used to remove the specimen after a thoracoscopic lobectomy of a large stage I primary lung cancer.

Follow-up extended through June 2003 so that all patients could be followed for at least 3 months. Two patients had less than 3 months of follow-up: 1 died in the perioperative period, and 1 left the country and was lost to further follow-up 1 month after biopsy of a benign lesion. Excluding these 2 patients, follow-up ranged from 3 to 29 months, with both an average and a median follow-up of 11 months. The average follow-up was also 11 months in the subset of patients who underwent a HATS procedure for metastasectomy with curative intent.

The patients' ages ranged from 22 to 81 years, with an average age of 57 years. Fourteen of the patients were male. The lesions were distributed as follows: 15% in the right upper lobe, 5% in the right middle lobe, 36% in the right lower lobe, 18% in the left upper lobe, and 23% in the left lower lobe. Nineteen of the patients had a history of extrathoracic cancer, including 1 patient with 2 extrathoracic malignancies (breast and colon cancer). The tumors included sarcoma (n = 7); colon carcinoma (n = 4); melanoma (n = 2); cervical carcinoma (n = 2); and breast, prostate, hepatocellular, oropharyngeal, and renal carcinoma in 1 patient each. These were diagnosed an average of 33 months previously, with a range of 0 to 100 months. In 3 of the patients with a history of cancer, the lesion was not thought to be a metastasis, whereas the others were approached with the intent of performing a curative metastasectomy.

The indications for surgery are shown in Table 1. The specific reasons for the substernal handport approach are also listed in Table 1. Of the 16 patients who underwent metastasectomy, the procedure was bilateral in 14, with the patients positioned supine. In 2 patients a unilateral approach was used. In 1 patient the location of the lesion was deemed to be too difficult to approach with the patient supine. The other patient had a solitary metastasis from prostate cancer, diagnosed 100 months previously, that had been treated for 3 years with hormonal therapy and chemotherapy, during which time no other metastases were observed. A unilateral approach was used in all of the patients who underwent HATS for biopsy of a pulmonary nodule.


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Table 1. Reasons for Surgery and for a Substernal Handport Approach

 

    Results
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 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
Metastatic cancer was documented in 14 (88%) of the 16 patients who underwent metastasectomy with curative intent. The lesions removed were benign in 5 of the 7 patients who had the HATS procedure to obtain a diagnostic biopsy sample (the lesion was a primary non–small-cell lung cancer in the other 2 patients).

The HATS approach was aborted in 8 cases (33%) and converted to either a sternotomy or a thoracotomy. This was done in 6 (38%) of 16 cases of metastasectomy and 2 (25%) of 8 cases of biopsy of an undiagnosed lesion. The HATS approach was abandoned because of dense adhesions in the pleural space in 1 case, because of anesthetic reasons in 1 case (desaturation and difficulty with 1-lung ventilation), and because of the location of the lesion in the other 6 cases (a very deep lesion in 2 cases, 1 of which ultimately required a lobectomy; a nodule located on the pulmonary artery in the fissure in 2 cases; a nodule adherent to the phrenic nerve and involving the diaphragm in 1 case; and a nodule adjacent to a fused fissure in 1 case).

The average length of stay (LOS) was 4.2 days (range, 2 to 18 days) for the 16 patients who underwent only a HATS procedure. Half of these patients were discharged within 3 days and 88% within 4 days. Identified reasons for extra days in the hospital were hemophilia requiring factor VIII administration (LOS 6 days), pain control (2 patients; LOS 4 days in each), desaturation (LOS 4 days), urinary tract infection (LOS 4 days), and acute respiratory distress syndrome (ARDS; LOS 18 days). Data on the length of chest drainage were available for 14 patients who underwent only a HATS procedure. The average duration of chest tube drainage was 2.25 days (range, 1 to 4 days). The tubes were removed within 2 days in 64% of the patients. Postoperative pain was managed in the vast majority of patients by intravenous narcotics with patient-controlled analgesia for the first 2 days and oral narcotics thereafter. None of the patients complained of pain at the time of the first postoperative clinic visit (10 to 14 days after operation).

Early complications (within 30 days) were seen in 3 of the patients who underwent only a HATS procedure. These included a urinary tract infection, a 3-day readmission for cellulitis around the epigastric incision that resolved with antibiotics alone, and ARDS. The latter patient died of fulminant ARDS, which occurred after an uneventful thoracoscopic right lower lobectomy for T2 N0 M0 non–small-cell lung cancer and a HATS approach for removal of the specimen. This patient had a poor preoperative diffusion capacity (diffusing capacity of the lung for carbon monoxide of 27% and maximal oxygen consumption of 16 mL · kg–1 · min–1 with exercise), but there was no obvious cause for the development of ARDS. None of the patients in whom the HATS approach was abandoned experienced any complications related to the substernal approach.

At the time of last follow-up, none of the 22 patients with at least 3 months of follow-up had any late complications related to the HATS approach. Specifically, there was no evidence of herniation into the substernal or pleural space on follow-up chest radiographs or CT scans. Ascites developed without leakage into the chest in 1 patient with end-stage cirrhosis, who underwent HATS for biopsy to rule out metastatic hepatocellular cancer before being listed for liver transplantation.

At the time of operation, we attempted to obtain a margin of at least 1 cm between the edge of the lesion and the staple line in all cases of metastasectomy. This was thought to have been achieved in all cases except 1, in which the HATS was abandoned and a right lower lobectomy was performed through a thoracotomy to achieve a negative margin. In fact, a microscopically negative margin was achieved in each of the 10 cases of metastasectomy with the HATS approach. A positive margin occurred in 2 of the 6 patients who underwent metastasectomy in which the HATS approach was abandoned (because of difficulty in achieving a complete resection by HATS in both). The actual distance of the lesion to the margin as reported by the pathologist was an average of 6 mm among all of the lesions resected in the 10 patients who underwent metastasectomy by HATS (range, 1 to 12 mm). However, data were missing for this measurement in 6 of the 19 lesions in these 10 patients. Furthermore, the measurement was taken after the staple line was trimmed away from the specimen. A margin of at least 5 mm was achieved in 58% of the metastasectomy specimens for which data were available.

Subsequent recurrence was seen in 4 of the 8 patients with metastases who underwent metastasectomy with HATS (those with benign disease and those in whom the HATS approach was abandoned were excluded). This involved the lung in all cases, combined with pleural disease or extrathoracic metastases in 1 patient each. A recurrence immediately adjacent to a staple line was seen in 1 of these patients, who was found simultaneously to have multiple pulmonary recurrences and multiple abdominal metastases from colon cancer. A repeat metastasectomy was undertaken in only 1 patient in whom recurrence developed.

More lesions were noted by palpation than were seen on the preoperative CT scan in 5 (31%) of the 16 patients in whom metastasectomy was planned. However, pathologic examination demonstrated additional metastasis in only 3 patients over what was noted by CT scan. In 1 additional patient, pathologic examination revealed multiple additional foci of cancer that were neither seen on CT nor palpated (this patient had recurrence in multiple sites after 5 months). In 11 patients thought preoperatively to have only unilateral metastases, but who underwent bilateral palpation, additional metastases were found in 3 (27%) and additional contralateral metastases in 2 (18%). In 6 patients thought preoperatively to have a solitary metastasis, but who underwent bilateral palpation, additional contralateral metastases were found in 1 (17%). In 8 patients thought preoperatively to have multiple metastases, but who underwent bilateral palpation, additional metastases were found in 3 (38%). As noted previously, no cancer was found in 2 patients, and 1 patient had only 2 metastases found by palpation and by pathologic examination, although 3 metastases were anticipated by the preoperative CT scan. The vast majority of CT scans were acquired on a spiral scanner with a single breath hold by using an 8-mm reconstruction algorithm. There was no difference in the patients who underwent a biopsy for diagnosis in the number of lesions seen on CT, noted during operation, and found by pathologic examination.


    Comment
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 
We have previously used a sternotomy as the standard approach for metastasectomy, because we believe that palpation of the lungs is needed to ensure a complete resection rather than reliance on visualization by CT scan alone. The substernal handport approach uses the inferior-most portion of a sternotomy incision and allows such easy palpation of the lungs that it has replaced sternotomy in our practice as the routine initial strategy in patients undergoing metastasectomy. The substernal handport has also replaced CT-guided needle localization for small lesions below the pleural surface. Adopting the HATS approach avoids the logistical issues of scheduling both the CT localization and operating room time, and it avoids having to guess whether such a localization procedure is necessary. The HATS approach allows biopsy of some lesions that are not amenable to a thoracoscopic approach alone. Furthermore, we find that palpation combined with a transcutaneous core needle biopsy is also an ideal diagnostic approach for lesions that are too deep to remove easily through a wedge biopsy when a diagnosis is needed before proceeding with lobectomy. We have also used the HATS approach recently to assess the invasion of lung cancer into posterior mediastinal structures (esophagus), and we found that it gave a valuable assessment, potentially avoiding a thoracotomy.

The HATS approach is simple to perform and is familiar to experienced thoracic surgeons who have used the substernal space for esophageal reconstruction. This technique allows the entire lung to be carefully palpated between the fingers of 1 hand, just as in a open approach. This is not the same as palpation of a limited portion of the lung with the tip of a finger inserted though a thoracoscopic port site. It also seems that the epigastric handport is less traumatic than bilateral removal of a costal cartilage or rib spreading to permit insertion of a hand for palpation.

We have encountered no early complications related to this procedure, although transient hypotension can occur when the left side is palpated in some patients if measures are not taken to minimize this. The fulminant ARDS that developed in 1 patient was quite clearly not related to the substernal approach, which was used strictly for removal of the resected right lower lobectomy specimen. This involved only a few minutes, and no hypotension occurred. ARDS after lobectomy is well described [3]. The average LOS after a HATS procedure is comparable to what is reported for wedge resection with thoracoscopy in other reports (2.4 to 5.1 days) [4–7]. We have also not seen any evidence of late complications. Although the number of patients is too small and the period of follow-up is too short to rule out a low incidence of complications, we conclude that the procedure is reasonably safe and that more widespread application is warranted.

Other authors have reported their experience in 22 patients with essentially the same approach [8]. No major morbidity or substernal hernias were seen, and the average hospital stay was 4.6 days—similar to our experience. In contrast to our experience, however, no patient in their series required conversion to an open approach. This may be because patients in their series were more carefully selected: patients with a history of thoracic surgery or pleuritis were excluded, as were patients with larger lesions or lesions that were more than 2 cm from the pleural surface. We considered such lesions (which were likely to be more difficult to resect) to be an indication for the HATS approach. It is also possible that the frequent use of a laser for pulmonary resection in the series by Ambrogi and associates [8] allowed resection to be accomplished more frequently than in our experience.

The margin of resection that can be obtained with a HATS approach seems reasonable. During operation, we sought to obtain a relatively wide margin (at least 1 cm) when performing metastasectomy. We are surprised that the margin reported by the pathologists was an average of only 6 mm, although this was measured after removal of the staple line. We do not know how this compares with the margin achieved when performing wedge resections through an open approach, because we were unable to find studies reporting such data. Finally, the HATS approach resulted in a complete resection in all cases, except in those in which it was abandoned because of difficulties. In these cases, even an open approach was also not able to achieve a complete resection in one third of the patients. Limited data are available on what constitutes an adequate margin [9]. Recurrences at the site of resection occurred in 3% of patients who underwent thoracoscopic resection of metastases in 1 report, in which an estimated margin of at least 1 cm was planned [10].

The overall recurrence rate of 40% among patients undergoing metastasectomy by HATS is similar to what has been found by others [9]. The 1 recurrence adjacent to a staple line involved a margin of only 1 mm (although it was microscopically negative). However, this patient had simultaneous extensive metastases both in the lungs and in the abdomen at the time of recurrence. The 14% (2/14) overall rate of incomplete resection in the experience reported here is similar to that of other studies (12% to 14%) [9, 11]. A 14% rate of pulmonary recurrence was observed in the series by Ambrogi and associates [8] with a similar substernal handport and thoracoscopic approach for metastasectomy. Thus, we conclude that the HATS approach does not compromise the ability to perform an adequate metastasectomy as compared with an open approach.

Whether palpation is still needed with modern helical CT scans has been studied in only limited series [8, 12]. Palpation has been widely reported to result in detection of 30% more lesions than are seen on a conventional CT scan [9, 11]. Helical CT has also been noted to detect approximately 20% more lesions than conventional CT [13, 14]. However, palpation compared directly with helical CT found 20% to 30% more lesions in 2 small series [8, 12]. Our limited experience here also suggests that palpation still detects more lesions than modern CT does. We were unable to specifically identify how many scans in our series were helical scans, because the radiology reports did not indicate this and we were unable to retrieve all of the scans. However, the vast majority were helical, single-breath-hold scans.

The HATS approach should be considered whenever a need for palpation of the lungs is anticipated, ie, during metastasectomy or for lesions that are small and not close to the pleural surface. The HATS approach may not provide adequate exposure in obese patients or in patients with extremely deep lesions (in whom a lobectomy may be required). With these exceptions, this approach is worth considering as the initial approach, even for difficult lesions. Although the approach was abandoned in a considerable minority of such patients, there is little to lose by initially attempting a HATS approach in most patients. This is because the incision needed for HATS is needed for a sternotomy as well.

We conclude that a substernal handport for palpation of the lungs is safe and allows an adequate resection of many pulmonary lesions that would otherwise require a sternotomy or a thoracotomy. It is easy to perform, is well tolerated by patients, and has an acceptably low rate of complications. The technique is useful in a variety of situations, such as localization of small lesions, exposure of lesions in difficult locations, biopsy under direct manual localization, and palpation of the lungs in patients with metastases. This technique deserves to be included in the standard armamentarium of approaches for thoracic surgery.


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Sakamoto K, Kumagiri Y, Ishii H, et al. Hand assisted thorascopic surgery (HATS) for metastatic lung tumors. Lung Cancer. 2003;41:S269 [Abstract]
  2. Mineo TC, Pompeo E, Ambrogi V, Pistolese C. Video-assisted approach for transxiphoid bilateral lung metastasectomy. Ann Thorac Surg. 1999;67:1808–1810[Abstract/Free Full Text]
  3. Kutlu CA, Williams EA, Evans TW, Pastorino U, Goldstraw P. Acute lung injury and acute respiratory distress syndrome after pulmonary resection: frequency and mortality. Ann Thorac Surg. 2000;69:376–380[Abstract/Free Full Text]
  4. Mack MJ, Hazelrigg SR, Landreneau RJ, Acuff TE. Thoracoscopy for the diagnosis of the indeterminate solitary pulmonary nodule. Ann Thorac Surg. 1993;56:825–832[Abstract]
  5. Allen MS, Deschamps C, Lee RE, Trastek VF, Daly RC, Pairolero PC. Video-assisted thoracoscopic stapled wedge excision for indeterminate pulmonary nodules. J Thorac Cardiovasc Surg. 1993;106:1048–1052[Abstract]
  6. Hazelrigg SR, Magee MJ, Cetindag IB. Video-assisted thoracic surgery for diagnosis of the solitary lung nodule. Chest Surg Clin North Am. 1998;8:763–774[Medline]
  7. Hazelrigg SR, Nunchuck SK, LoCicero J. Video Assisted Thoracic Surgery Study Group data. Ann Thorac Surg. 1993;56:1039–1044[Abstract]
  8. Ambrogi V, Paci M, Pompeo E, Mineo TC. Transxiphoid video-assisted pulmonary metastasectomy: relevance of helical computed tomography occult lesions. Ann Thorac Surg. 2000;70:1847–1852[Abstract/Free Full Text]
  9. Sadoff JD, Detterbeck FC. Pulmonary metastases from extrapulmonary cancer. Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: Saunders; 2001. p. 450–464
  10. Lin JC, Wiechmann RJ, Szwerc MF, et al. Diagnostic and therapeutic video-assisted thoracic surgery resection of pulmonary metastases. Surgery. 1999;126:636–642[Medline]
  11. The International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997;113:37–49[Abstract/Free Full Text]
  12. Diederich S, Semik M, Lentschig MG, et al. Helical CT of pulmonary nodules in patients with extrathoracic malignancy. CT-surgical correlation. AJR Am J Roentgenol. 1999;172:353–360[Abstract/Free Full Text]
  13. Collie DA, Wright AR, Williams JR, et al. Comparison of spiral-acquisition computed tomography and conventional computed tomography in the assessment of pulmonary metastatic disease. Br J Radiol. 1994;67:436–444[Abstract/Free Full Text]
  14. Remy-Jardin M, Remy J, Giraud F, et al. Pulmonary nodules: detection with thick-section spiral CT versus conventional CT. Radiology. 1993;187:513–520[Abstract/Free Full Text]



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