JTCS Click here to go to SJM website.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Rebecca P. Petersen
William R. Burfeind, Jr
Walter Wolfe
Thomas A. D’Amico
David H. Harpole, Jr
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Petersen, R. P.
Right arrow Articles by Harpole, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petersen, R. P.
Right arrow Articles by Harpole, D. H., Jr
Related Collections
Right arrowRelated Article

J Thorac Cardiovasc Surg 2007;133:104-110
© 2007 The American Association for Thoracic Surgery

General Thoracic Surgery

Improved survival with pulmonary metastasectomy: An analysis of 1720 patients with pulmonary metastatic melanoma

Rebecca P. Petersen, MD, MSca, Steven I. Hanish, MDa, John C. Haney, MDa, Charles C. Miller, III, PhDb, William R. Burfeind, Jr, MDa, Douglas S. Tyler, MDa, Hilliard F. Seigler, MDa, Walter Wolfe, MDa, Thomas A. D’Amico, MDa, David H. Harpole, Jr, MDa,*

a Department of Surgery, Duke University Medical Center, Durham, NC, Texas
b Department of Cardiothoracic and Vascular Surgery, University of Texas–Houston Health Science Center, Houston, Texas.

Read at the Eighty-sixth Annual Meeting of The American Association for Thoracic Surgery, Philadelphia, Pa, April 29–May 3, 2006.

Received for publication April 28, 2006; revisions received July 18, 2006; accepted for publication August 7, 2006.

* Address for reprints: David H. Harpole, Jr, MD, Department of Surgery, Duke University Medical Center, Box 3617, Durham, NC 27710. (Email: harpo002{at}mc.duke.edu).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
OBJECTIVES: The outcomes of patients with metastatic melanoma are poor. Although prognostic models have been developed to predict the occurrence of pulmonary metastasis from cutaneous melanoma, few data exist to define the outcomes of these patients once metastasis has occurred. The objective of this study was to discriminate predictors of survival for patients with pulmonary metastatic melanoma.

METHODS: We found 1720 patients with pulmonary metastasis listed in a prospective comprehensive cancer center database of 14,057 consecutive patients with melanoma (Jan 1, 1970–June 1, 2004). Demographic and histopathologic data, time and location of recurrences, number of pulmonary nodules, and subsequent therapies were collected. Univariate and multivariate Cox proportional hazards models were used to identify predictors of survival for patients with pulmonary metastatic melanoma.

RESULTS: The median survival was 7.3 months after development of pulmonary metastasis. Significant predictors of survival from the multivariate model included nodular histologic type (P = .033), disease-free interval (P < .001), number of pulmonary metastases (P = .012), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001). Interactions were identified between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Surgery was associated with a survival advantage of 12 months for patients with a disease-free interval longer than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without extrathoracic metastasis (18 vs 8 months, P < .01).

CONCLUSIONS: When all other identified risk factors were controlled for mathematically, metastasectomy maintained a significant survival advantage for patients with pulmonary metastatic melanoma. These data support the role of surgery for a select subset of patients with pulmonary metastasis.

Abbreviations and Acronyms CT = computed tomography; PET = positron emission tomography


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
GoIn 2004, approximately 55,100 people in the United States were diagnosed with cutaneous melanoma, and the incidence only continues to rise.1Go Approximately 30% of patients with cutaneous melanoma have metastatic disease develop, resulting in a dismal prognosis with a median survival of only 6 to 8 months and 5-year survival of less than 5%.2,3Go More than 80% of patients with metastatic melanoma initially show only one distant organ site involved, most commonly the lung.3-5Go Approximately 40% of patients with metastatic melanoma initially show isolated pulmonary metastasis.3Go

Once distant metastasis has developed, the treatment options remain limited. This is largely due to the failure of numerous systemic therapies, including chemotherapy, immunotherapy, and more recently molecular targeted agents, to improve overall survival in patients with stage IV disease. Surgical therapy, however, has been shown in several studies to be associated with a 5-year survival as high as 39%,6Go as opposed to a 3% to 5% 5-year survival for nonsurgically treated patients.2,7-10Go These findings suggest that a select subset of patients with pulmonary metastatic melanoma may benefit from metastasectomy. Several large studies of patients with pulmonary metastatic disease have determined prognostic factors for survival, but these have included patients with a variety of primary tumor types and have failed to discriminate melanoma-specific prognostic factors. The objective of this study was to discriminate predictors of survival in patients with pulmonary metastatic melanoma.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Patient Population
This study was reviewed and approved by the Duke institutional review board. Among the 14,057 patients with primary melanoma who were initially evaluated at the Duke Comprehensive Cancer Center between January 1, 1970, and December 31, 2004, we found 1720 patients with metastatic pulmonary melanoma. The database was prospectively maintained, and baseline demographic data, time and location of primary tumor, histopathologic data, subsequent therapies (immunotherapy, chemotherapy, nodal dissections, and other resections), overall and cancer-specific survivals, and time and location of metastases were available for all patients. All patients with primary melanoma were followed up by clinical examination every 6 months for 5 years after the initial diagnosis and then annually thereafter. In addition, annual surveillance chest radiography was routinely performed for all patients to detect pulmonary metastasis.

Statistical Methods
Univariate and multivariate regression analyses with a Cox proportional hazards model were performed to examine the relationship between potential prognostic factors and overall survival for patients with metastatic pulmonary melanoma. The following variables were analyzed: age, sex, race, primary site, histologic type, Clark level, Breslow thickness, ulceration of the primary lesion, regional lymph node status, number of pulmonary metastases, disease-free interval between initial diagnosis and development of pulmonary metastasis, presence of extrathoracic metastasis, subsequent therapies (immunotherapy and chemotherapy) and performance of pulmonary metastasectomy. Predictor variables identified in the univariate analysis with a P value less than .1 were further examined in a multiple Cox proportional hazards model.

Overall survival was defined as the time between the initial diagnosis of pulmonary metastasis and the date of last follow-up or death. Probabilities for development of pulmonary metastasis and overall survival were estimated with the Kaplan–Meier method. Kaplan–Meier survival analyses stratifying on significant predictor variables identified in the multivariate analysis were also performed, and differences were tested with the log-rank test. Analyses were carried out with Intercooled STATA version 9.0 software (Stata Corporation, College Station, Tex).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
The estimated risks of development of pulmonary metastasis for the entire melanoma population (n = 13,565) were 13% at 5 years, 17% at 10 years, and 23% at 20 years after initial diagnosis (Figure E1). Patients who had unknown primary tumors or who had pulmonary metastasis at initial presentation were excluded from this analysis (n = 492). The median follow-up of living patients was 65 months (0.1-524 months).


Figure 1
View larger version (10K):
[in this window]
[in a new window]

  		Figure E1. Risk of development of pulmonary metastasis (n = 13,565).

 
The overall survivals for patients with pulmonary metastatic melanoma (n = 1720) were 34% at 1 year, 14% at 2 years, and 6% at 5 years (Figure E2). Patient demographic and melanoma histopathologic characteristics are displayed in Table 1. The most common method of diagnosis for pulmonary metastatic melanoma was chest radiography (n = 774). The remaining cases were diagnosed by chest computed tomography (CT, n = 410), surgery (n = 318), transthoracic needle aspiration (n = 192), bronchoscopic biopsy (n = 18), and autopsy (n = 8). For patients undergoing surgery, the most common approach was unilateral thoracotomy (n = 255), followed by thoracoscopic surgery (n = 40) and bilateral thoracotomy (n = 23). The most common type of anatomic resection was stapled wedge (n = 210), followed by lobectomy (n = 96), segmentectomy (n = 9), and pneumonectomy (n = 3).


Figure 2
View larger version (11K):
[in this window]
[in a new window]

  		Figure E2. Overall survival for patients with metastatic pulmonary melanoma (n = 1720).

 

View this table:
[in this window]
[in a new window]

  		TABLE 1. Comparison of total patients, surgical patients, and nonsurgical patients (n = 1720)
 
Among the demographic and histopathologic characteristics, age older than 50 years (P = .01), African American race (P = .03), nodular histologic type (P = .01), Breslow thickness (1-4 mm P = .01 and >4 mm P = .002), ulceration of the primary lesion (P = .003), positive regional lymph nodes (P = .001), more than 2 pulmonary metastases (P < .001), disease-free interval (<1 year P < .001 and 1-5 years P < .001), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001) were found to be significant univariate predictors of overall survival. When examined in a multivariate model, nodular histologic type, disease-free interval, number of pulmonary metastases, presence of extrathoracic metastasis, and performance of pulmonary metastasectomy were found to be independent predictors of overall survival (Table 2).


View this table:
[in this window]
[in a new window]

  		TABLE 2. Independent predictors of overall survival in patients with pulmonary metastatic melanoma
 
Interactions were found between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Among patients with a disease-free interval longer than 5 years, surgery was associated with a survival advantage of 12 months (19 vs 7 months, P < .01). In patients without evidence of extrathoracic metastasis, pulmonary metastasectomy was associated with a survival advantage of 10 months (18 vs 8 months, P < .01; Figure E4). After stratification on number of preoperative risk factors identified in the multivariate analysis, patients with no risk factors, 1 risk factor, 2 risk factors, and 3 or more risk factors had 5-year survivals of 26%, 11%, 4%, and 2%, respectively (Figure 1).


Figure 4
View larger version (20K):
[in this window]
[in a new window]

  		Figure E4. Overall survival by metastasectomy and presence of extrathoracic metastasis (n = 1065).

 

Figure 1
View larger version (31K):
[in this window]
[in a new window]

  		Figure 1. Overall survival by number of preoperative risk factors (n = 1720).

 
Two hundred forty-nine (78%) of the 318 patients who underwent metastasectomy had complete resection, and patients with incomplete resection were more likely to have multiple pulmonary metastases. Otherwise, there were no significant differences with regard to histologic type, diseases-free interval, or history of treated nonpulmonary distant metastasis (Table E1). Patients undergoing metastasectomy who had complete pathologic resection had a median survival of 19 months and a 5-year survival of 21%, compared with a median survival of 11 months and a 5-year survival of only 13% for patients with incomplete resection (P < .0001; Figure E5). Fifteen patients (5%) underwent repeated surgical resections. The median time to repeated metastasectomy was 9 ± 6.3 months. There was no significant difference in survival between patients undergoing single metastasectomy and those patients undergoing repeated metastasectomies (median survivals 17 months and 15 months, respectively, P = .9).


View this table:
[in this window]
[in a new window]

  		TABLE E1. Surgery-only patients, by complete and incomplete resection (n = 318)
 

Figure 5
View larger version (23K):
[in this window]
[in a new window]

  		Figure E5. Overall survival by complete resection, incomplete resection, and nonsurgical treatment (n = 1720).

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
In this study, we found several independent prognostic factors to be associated with overall survival for patients with pulmonary metastatic melanoma. Patients who had nodular histologic type of the primary lesion, greater number of pulmonary metastases (≥2), shorter disease-free interval (<5 years), or evidence of extrathoracic metastasis had a poor prognosis, with a median survival of less than 8 months. In contrast, patients selected for pulmonary metastasectomy were found to have a much higher median survival of 17 months. The greatest benefit from metastasectomy was realized in patients who had a prolonged disease-free interval of greater than 5 years and no evidence of extrathoracic metastasis.

Despite the many therapeutic advances that have been made during the past three decades for early-stage melanoma, the current treatment options for stage IV melanoma remain limited. Chemotherapy with dacarbazine remains the criterion standard, despite the lack of evidence of improved survival for patients with stage IV disease.11Go In addition, there remains no role for immunotherapy in patients with metastatic melanoma. The reported response rates have been well below 20% for a variety of immunotherapies, including cytokines, monoclonal antibodies, and vaccination strategies with synthetic peptides, naked DNA, dendritic cells, recombinant viruses, and so on.12Go Unfortunately, as a result of these dismal response rates and lack of phase 3 studies demonstrating improved overall survival for these systemic agents, surgery remains the only hope for improved survival for a select subset of patients with stage IV disease.

Previous observational studies of patients with metastatic melanoma have revealed varying results in identifying significant prognostic factors; however, several variables have remained constant from study to study, specifically the number of pulmonary nodules, the disease-free interval, and the presence of extrathoracic metastasis.2,9,10,13Go In our previous analysis, performed more than 15 years ago, regional lymph node involvement and treatment with dacarbazine-based chemotherapy were found to be independent significant predictors of survival; however, both of these had questionable clinical significance, with a survival advantage of less than 2 months.9Go In this larger analysis, these factors were not found to be significant predictors. The finding that chemotherapy was not associated with survival is consistent with randomized controlled trials investigating the efficacy of systemic therapy in this patient population.14-17Go

In contrast to systemic therapy, surgical management continues to be the primary treatment modality for patients with metastatic melanoma. Unfortunately, surgery is not appropriate for all patients, and patient selection criteria remain controversial. Although we did not directly determine predictors of survival among patients undergoing surgery, these patients typically had a limited number of lung nodules, no evidence of extrathoracic metastasis, and a prolonged disease-free interval.

All surgical patients included in this analysis underwent resection with curative intent only. None of the patients undergoing surgery in our series had grossly positive margins (R2). Incomplete resection in this study was defined as lack of evidence of gross residual disease; on further histologic examination, however, the margins of the specimen were judged to be microscopically incomplete (R1). This may explain why patients with "incomplete resection" in our series had a 5-year survival of 13%, as compared with a 0% 5-year survival in the study reported by Leo and colleagues,10Go in which incomplete resection was defined as either R1 (microscopically incomplete) or R2 (grossly incomplete). There is evidence to suggest that by reducing the tumor burden, the immune system’s antitumor response may be enhanced.18Go Together, these findings support the continued use of metastasectomy for select patients with melanoma and pulmonary metastasis.

The strengths of our study include prospective data collection, complete follow-up on all patients, and large sample size. Despite our attempts to control for many of the potential selection factors by accounting for clinical and pathologic characteristics of the metastasis, as well as characteristics of the individual patients, our analysis is most likely limited by patient selection bias. For example, it is challenging to account for the judgment of individual surgeons in determining eligibility for resection. In addition, we were unable to account for other comorbidities that also may have influenced the selection of patients for surgery and survival.

Although our study represents one of the largest series of pulmonary metastasectomies for melanoma, another limitation is that these data were collected during a span of 35 years. As a consequence, changes in imaging technology and less-invasive surgical techniques may also have influenced the selection and outcomes of patients. In an international registry of lung metastasis of 2988 patients with available preoperative radiologic and postoperative pathologic assessments, accuracy rates of 61% and 75% were reported for patients with bilateral and unilateral disease, respectively. In addition, radiologic assessment was found to underestimate number of pulmonary metastases by 16% to 25%.13Go Moreover, data from the recently completed National Lung Cancer Screening Trial (n = 50,000) underscore the accuracy of newer generation chest CT scans that detect all lung abnormalities larger than 2 mm. Most patients in the earlier phase of our series had their disease diagnosed by routine surveillance chest radiography alone; however, patients enrolled in the latter half of the study underwent CT, and more recently high-resolution helical CT with positron emission tomography (PET).

In addition, improvements in surgical technologies have led to an evolution of the standard approach for metastasectomy. Currently, we no longer routinely perform open thoracotomy at our institution, preferring limited-access (video-assisted) resections, either stapled wedge or lobectomy. This is accomplished by initially exploring the thorax thoracoscopically to inspect both the visceral and parietal pleural surfaces to exclude pleural dissemination. Pulmonary nodules for intended resection are then located with precise anatomic information from the CT scan and also by palpation of lesions with a long, oval-ringed clamp (thoracoscopic Foerster clamp). Occasionally, nodules in the anterior segments may also be palpated with the index finger through the anterior access incision. It is possible that these differences in operative technique may have also influenced patient selection for metastasectomy.

Surgical therapy for pulmonary metastasis is not a new treatment modality, as the first metastasectomy was performed more than 50 years ago,19Go but controversy still exists regarding the benefits of resection for patients with stage IV melanoma. Several studies have demonstrated improved survivals of 18% to 39% for selected patients with pulmonary metastasis undergoing resection, which is a significant improvement relative to the 5-year survival of 3% to 5% for nonsurgically treated patients.2,6-10Go In our study of 1720 patients, we also observed a significant survival benefit from pulmonary metastasectomy for a subset of patients with metastatic pulmonary melanoma. Our findings support the continued use of surgical resection for patients with the following criteria: (1) limited number of pulmonary metastases (<2), (2) prolonged disease-free interval, and (3) negative results of PET or CT scan for extrathoracic pulmonary metastasis. A simple model that is based on number of preoperative risk factors is provided as an aid for clinicians when selecting patients appropriate for metastasectomy (Figure E3).


Figure 3
View larger version (19K):
[in this window]
[in a new window]

  		Figure E3. Overall survival by metastasectomy and disease-free interval (n = 414).

 

Earn CME credits at http://cme.ctsnetjournals.org

 


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin 2004;54:8-29.[Abstract/Free Full Text]
  2. Essner R, Lee JH, Wanek LA, Itakura H, Morton DL. Contemporary surgical treatment of advanced-stage melanoma. Arch Surg 2004;139:961-967.[Abstract/Free Full Text]
  3. Balch CM, Soong SJ, Murad TM, Smith TW, Maddox WA, Durant JR. A multifactorial analysis of melanoma. IV. prognostic factors in 200 melanoma patients with distant metastasis (stage III). J Clin Oncol 1983;1:126-134.[Abstract]
  4. Barth A, Wanek LA, Morton DL. Prognostic factors in 1521 melanoma patients with distant metastases. J Am Coll Surg 1995;181:193-201.[Medline]
  5. Lee ML, Tomsu K, Von Eschen KB. Duration of survival for disseminated malignant melanoma: results of a meta-analysis. Melanoma Res 2000;10:81-92.[Medline]
  6. Tafra L, Dale PS, Wanek LA, Ramming KP, Morton DL. Resection of adjuvant immunotherapy for melanoma metastatic to the lung and thorax. J Thorac Cardiovasc Surg 1995;110:119-129.[Abstract/Free Full Text]
  7. Wong JH, Euhus DM, Morton DL. Surgical resection for metastatic melanoma of the lung. Arch Surg 1988;123:1091-1095.[Abstract/Free Full Text]
  8. Gorenstein LA, Putnam JB, Natarajan G, Balch CA, Roth JA. Improved survival after resection of pulmonary metastases from malignant melanoma. Ann Thorac Surg 1991;52:204-210.[Abstract]
  9. Harpole DH, Johnson CM, Wolfe WG, George SL, Seigler HF. Analysis of 945 cases of pulmonary metastatic melanoma. J Thorac Cardiovasc Surg 1992;103:743-750.[Abstract]
  10. Leo F, Cagini L, Rocmans P, Cappello M, Van Geel A, Maggi G, et al. Lung metastases from melanoma: when is surgical treatment warranted?. Br J Cancer 2000;83:569-572.[Medline]
  11. Tarhini AA, Agarwala SS. Interleukin-2 for the treatment of melanoma. Curr Opin Investig Drugs 2005;6:1234-1239.[Medline]
  12. Riker AI, Jove R, Daud AI. Immunotherapy as part of a multidisciplinary approach to melanoma treatment. Front Biosci 2006;11:1-14.[Medline]
  13. Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37-49.[Abstract/Free Full Text]
  14. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999;17:2105-2116.[Abstract/Free Full Text]
  15. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am 2000;6(1):S11-S14.[Medline]
  16. Mandara M, Nortilli R, Sava T, Cetto GL. Chemotherapy for metastatic melanoma. Expert Rev Anticancer Ther 2006;6:121-130.[Medline]
  17. Alexandrescu DT, Dutcher JP, Wiernik PH. Metastatic melanoma: is biochemotherapy the future?. Med Oncol 2005;22:101-110.[Medline]
  18. Dreno B, Nguyen JM, Khammari A, Pandolfino MC, Tessier MH, Bercegeay S, et al. Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma. Cancer Immunol Immunother 2002;51:539-546.[Medline]
  19. Oschner A, Rush V. Treatment of pulmonary metastatic disease. Surg Clin North Am 1966;46:1469-1474.[Medline]

Related Article

Discussion
J. Thorac. Cardiovasc. Surg. 2007 133: 109-110. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
L. Erhunmwunsee and T. A. D'Amico
Surgical management of pulmonary metastases.
Ann. Thorac. Surg., December 1, 2009; 88(6): 2052 - 2060.
[Abstract] [Full Text] [PDF]

Home page
 CA Cancer J ClinHome page
R. D. Timmerman, C. S. Bizekis, H. I. Pass, Y. Fong, D. E. Dupuy, L. A. Dawson, and D. Lu
Local Surgical, Ablative, and Radiation Treatment of Metastases
CA Cancer J Clin, May 1, 2009; 59(3): 145 - 170.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
K. Shikuma, M. Omasa, Y. Yutaka, M. Okuda, and T. Taki
Treatment of Primary Melanoma of the Lung Monitored by 5-S-Cysteinyldopa Levels
Ann. Thorac. Surg., April 1, 2009; 87(4): 1264 - 1266.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
Y. Tanaka, Y. Maniwa, W. Nishio, M. Yoshimura, and Y. Okita
The optimal timing to resect pulmonary metastasis
Eur. J. Cardiothorac. Surg., June 1, 2008; 33(6): 1135 - 1138.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
M. Fouad Ismail
Pulmonary metastatic melanoma.
J. Thorac. Cardiovasc. Surg., October 1, 2007; 134(4): 1097 - 1097.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Rebecca P. Petersen
William R. Burfeind, Jr
Walter Wolfe
Thomas A. D’Amico
David H. Harpole, Jr
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Petersen, R. P.
Right arrow Articles by Harpole, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petersen, R. P.
Right arrow Articles by Harpole, D. H., Jr
Related Collections
Right arrowRelated Article

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS