Minimally invasive thoracoscopic approach to pulmonary metastasectomy for esophageal cancer: a narrative review

Introduction

Background

Esophageal cancer is the tenth most common cancer in the world (1). Until recently, esophageal cancer had a poor prognosis for majority of the patients. The outcomes and prognoses of esophageal cancer have drastically improved for all stages of disease over the last two decades, with the advent of neoadjuvant chemoradiation, surgical approaches, and targeted immunotherapy (2-6). The CheckMate 577 trial showed that after neoadjuvant chemoradiation therapy and surgical resection, the group who received nivolumab had a median disease-free survival of 22.4 months, compared to 11 months in the placebo group (4). Makowiec et al. reviewed 304 patients with esophageal cancer at their institution over two decades, and they found that the median survival increased over time from 18 to 59.3 month from 1988 to 2011 (7). However, the recurrence rate after multimodal therapy with curative intent remains high. About 43.3–48% of patients recur despite maximal multimodal therapy, and 20% to 41.4% of them have distant recurrence (2,6). Lung is one of the most common sites of recurrence from esophageal cancer. Metastatic esophageal cancer has poor prognosis and most patients have multiple sites of metastases that preclude treatment with curative intent. However, there is a small group of patients that develop single metastasis or oligometastases. The determination as to what number or sites involved qualified as oligometastases vary in the literature. It is reasonable to consider limited number of metastases but also limited sites of metastases as oligometastatic disease (8).

Pulmonary metastasectomy is most commonly used to resect single metastasis or oligometastases in the setting of sarcoma and colorectal cancer, and its role in other cancer types remains unclear. Depypere et al. reviewed 766 patients with recurrent disease after multimodality treatment for esophageal cancer, where 471 patients underwent treatment for their recurrent disease. In the subgroup of 110 patients with solitary solid organ metastasis in a resectable organ, patients who underwent surgical resection had longer survival compared with those who underwent non-surgical treatments (54.8 vs. 11.6 months) (9). As for treatment of oligometastases after esophagectomy, Ghaly et al. did not find a survival advantage in patients who were treated with surgery with or without chemotherapy and radiation. The only significant independent predictor for survival after recurrence was the median time to recurrence (10). The traditional gold standard of pulmonary metastasectomy is performed through a thoracotomy. The rationale is to allow bimanual palpation and examination of the entire lung parenchyma. A thorough palpation is limited with a minimally invasive approach, as the access incision is usually not of adequate size to allow an entire hand to traverse. Past studies have shown video-assisted thoracoscopic surgery (VATS) approach is associated with a better overall survival than thoracotomy, as well as reduced hospital stay, lower cost, faster recovery and fewer complications (11-13).

Rationale and knowledge gap

There was a previous well-written review article by Schizas et al. (14) on pulmonary metastasectomy for oligometastases from esophageal cancer in 2018. Ten studies prior to 2018 were included in Schizas et al.’s very thoroughly written review article, in which they made a table that clearly listed the number of patients, lesions, type of resection, and median survival from these studies. Two additional studies were published since that review, which will be included in this review. This review discusses several gaps in on this topic in the context of thoracoscopic approach to pulmonary metastasectomy for esophageal cancer, including patient selection based on prognostic factors from past studies, the choice of anatomic vs. non anatomic pulmonary resection, the necessity of mediastinal lymph node dissection, comparison with stereotactic body radiotherapy (SBRT) and thermal ablation, and technical challenges and solutions to thoracoscopic approach compared to traditional thoracotomy.

Objective

The purpose of this review is to summarize the studies on minimally invasive thoracoscopic approach to pulmonary metastasectomy for solitary metastasis and oligometastases to the lung. We will compare surgical outcome to alternative therapy, discuss the role and challenges of thoracoscopic approach and solutions, and propose directions for future studies. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-23-9/rc).

Methods

The search strategy is shown in the Table S1. A literature search was conducted using PubMed and Cochrane databases on September 30, 2022, including all studies from 1966 to September 30, 2022. The following MeSH terms were applied: “(lung neoplasms-secondary) and (esophageal neoplasm) and (metastasectomy) or (stereotactic body radiotherapy) or (ablation techniques)”. Case reports, case series and reviews were included. Studies that did not report on outcomes or were not written in the English language were excluded.

There were two additional studies that were performed since Schizas et al.’s review; they were by Komatsu et al. and Seesing et al. (15,16). The cohorts in both studies did not have any patients with extrapulmonary metastases. Despite the advances in surgical and medical treatment of advanced stage of esophageal cancer, no additional studies were found after 2019. Seesing et al.’s cohort on pulmonary resection included patients with esophageal, gastroesophageal junction (GEJ) and gastric cardia patients, and did not include any tumors of the gastric body, antrum or pylorus.

Pulmonary metastasectomy

When comparing surgical with non-surgical treatments, both the benefits and risks need to be balanced on an individual basis. The benefits are compared in terms of accurate diagnosis and staging, local control, and survival outcomes. The risks are assessed with post-procedure complication types and severity, re-interventions for local control, and level of invasiveness. The technological advances in thoracoscopy and nodule targeting in recent years have made pulmonary resections better tolerated.

Pulmonary metastasectomy for esophageal cancer is not commonly performed since most distant disease occurs in a disseminated fashion. It is uncommon to find single metastasis or oligometastases in esophageal cancer that is limited to one organ system and that can be resected with curative intent (2,6). Kobayashi et al. showed the importance of poor prognostic factors (17). They found that the cumulative survival for the 12 patients in their series was 64.9% at 5 years, and those with one or more risk factors was 0%. Patient selection is therefore of utmost importance to maximize the benefits of a metastasectomy with curative intent. Table 1 summarizes several studies that analyzed the prognostic factors for patients who underwent pulmonary metastasectomy (15,17-21). Factors that showed a near-significant level of trend were also included in Table 1, since most studies on this topic have small sample sizes. Nodal status of the esophageal cancer was found to be significant in some studies, though not consistently studied. Across studies, disease-free interval (DFI) and presence of extrapulmonary metastatic disease were found to be important prognostic factors for survival.

Most of the past studies on this topic took place in Japan, where the predominant histology is squamous cell carcinoma (SCC), and followed by relatively few adenocarcinoma (AC). Dresner et al. showed that distant dissemination occurred with higher frequency with AC than SCC (2). The majority of the patients in Seesing et al.’s study had AC (9 out of 15) (16). Their study was not included in Table 1 as they did not analyze the prognostic factors. They reported a 5-year overall survival of 53%. They performed 11 wedge resections and 3 lobectomies with thoracotomy approach, with median length of stay of 7 days and four patients had complications of Clavien-Dindo grade 3.

Choosing the right operation

The choice of pulmonary resection is mostly determined by tumor location and surgeon’s experience and judgment. Wedge resections are the predominant type performed in most studies. However, segmentectomy and lobectomy are performed for non-peripherally located nodules. Some surgeons may choose to perform anatomic resection if there is significant suspicion that the cancer could be a new primary lung cancer. This diagnostic uncertainly is especially pronounced in the setting of SCC of the esophagus with a solitary lung nodule that is also SCC. Surgical pathology cannot always reliably decipher the origin of the SCC (22). For example, Sarsam et al. performed pulmonary metastasectomy from various primary tumors in 168 patients. Final surgical pathology revealed significant number of non-metastases, with 6 benign lesions and 5 primary lung cancer (23).

Few past studies report whether mediastinal or hilar lymph nodes were sampled at the time of pulmonary resections in the setting of pulmonary metastasectomy. Many surgeons do not routinely perform lymph node sampling or dissection during pulmonary metastasectomy, especially if the nodule is amenable to a wedge resection. Mediastinal and hilar lymph node dissection adds complexity and operative time to a straight-forward wedge resection. However, when a segmentectomy or lobectomy is performed, hilar lymph node dissection aids the resection by revealing anatomic structures, and it is performed without much added effort from the surgeon. The role of lymphadenectomy is not to increase survival, but to help predict prognosis. Ercan et al. analyzed 70 patients who underwent pulmonary metastasectomy for various cancer types, such as colon, renal cell, melanoma, endometrial, salivary gland, genitourinary cancers. Of all the patients, 28.6% were found to have lymph node metastases, with 9 patients having N1 metastases alone, 8 patients having N2 metastases alone, and 3 patients with metastases in both N1 and N2 stations. The 3-year survival was significantly lower among those with any lymph node metastases (38% compared to 69%), and they also found that survival was not improved when only N1 lymph nodes were involved (24). Specifically for esophageal cancer, Shiono et al.’s study included 10 patients with pulmonary metastases from esophageal cancer that underwent pulmonary metastasectomy and lymph node dissection, with one patient having lymph node metastasis (10%). In their total cohort of 617 patients, the 5-year survival was significantly higher in patients without lymph node metastases (53.8%), compared to those with hilar (39.4%) and mediastinal (30.8%) metastases (25). It is unclear if lymph node dissection could decrease local recurrence by removing as much nidus of disease as possible. In the setting of metastasectomy, where the disease is spread by hematogenous route, removing local nidus of lymph node disease is unlikely to change survival. However, it could affect decisions on adjuvant therapy.

Comparison to alternative therapies

Primary tumors and metastases to the lung can be treated with SBRT and thermal ablative therapy, such as radiofrequency ablation (RFA) and microwave ablation. SBRT is more commonly used. Local control in the lung and liver is about 66% to 80% in 3 years (26,27). The size of lesion is a major factor in lesion local control, with lesions smaller than 3 cm having 100% control at 2 years, compared to 77% if larger than 3 cm (28). A nationwide survey in Japan focused on pulmonary oligometastases treated by SBRT included 114 cases from esophageal cases out of total of 1,378. The median survival time was 27.1 months for the esophageal group (29). Yamamoto et al. specifically studied SBRT for pulmonary oligometastases from esophageal cancer in 114 patients, and showed a 5-year overall survival rate of 37.5% with median survival of 27.1 months. The lesion local control rate was 81.4% at 3 and 5 years. Adverse events among 90 of the 114 patients included radiation pneumonitis in 6 patients, radiation dermatitis and gastrointestinal complications. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance score was an independent predictor of overall survival. DFI, chemotherapy, and history of local therapy for metastasis were predictors of freedom from further metastasis but not overall survival (30). One important thing to note is that pre-treatment tissue diagnosis may not always be obtained, and surgical metastasectomy studies have shown pathologic discordance with clinical suspicion (23).

The literature on thermal ablative therapy for pulmonary oligometastases from esophageal cancer is scarce. Matsui et al.’s study included 26 patients who underwent RFA, and showed 3-year overall survival of 38.4%, and local tumor progression in 25.8% of the 31 tumors treated. The complication profile from this study included pneumothorax after 37% of the sessions, pulmonary fistula, reactive pneumonitis, pleural effusion, hemothorax (31).

Comparing studies specifically on treatment of pulmonary oligometastases from esophageal cancer, surgical metastasectomy and SBRT have similar percent 5-year overall survival in the 30s to 40s range. Surgical metastasectomy with R0 resection and lymph node sampling has the added advantage of diagnostic certainty, reliable local control and prognostication for future therapies. The advantage of SBRT is that it is an outpatient, non-invasive treatment. Patients with long DFI, no extrapulmonary metastases, good functional status can have a good survival outcome with either surgical resection or SBRT. However, those with poor prognostic factors may be better served with SBRT.

Challenges of pulmonary metastasectomy

There are several challenges in pulmonary metastasectomy for esophageal cancer. When the primary esophageal cancer was treated with esophagectomy with curative intent, the pleural cavity could contain significant amount of adhesions depending on operative approach and history of anastomotic leak. Extensive adhesions could obscure operative field and prolong operative time and increase rate of conversion from thoracoscopic approach to thoracotomy. The next challenge is the location of the metastases. Lesions located on or near the visceral surface can often be visible or palpable with thoracoscopic approach. However, when the lesion of interest is small and deep, palpation from thoracoscopic approach can become difficult. There are several strategies in dealing with this. One can locate the access incision or specimen extraction incision close to the visceral surface overlying the lesion, and direct digital palpation can be more sensitive than using an instrument to rub over the surface of the lung alone. However, there remains the question of whether bimanual palpation is critical. Some studies show that bimanual palpation through thoracotomy found more nodules than VATS (32,33). One of the factors for this discrepancy is using computed tomography image with slice thickness of 3–5 mm (34). In the current era where the technology of slice thickness 0.5–1 mm is widely used, fewer such nodules may be missed (23). Positron emission tomography (PET) scan is also valuable in detecting nodules that are more than 1 cm. It is reasonable to question whether the risks of resecting every tiny metastasis of a few millimeters size through a thoracotomy outweigh the benefits. In addition, with decreased morbidity from thoracoscopic approach, repeat metastasectomy does not carry the same morbidity as a re-do thoracotomy; SBRT always remains an alternative to surgical resection for undetected nodules that later grow to a significant size.

In recent years, there has been rapid development in technology used for pre-operative nodule localization. Deep nodules can be tagged with a hook wire or coil (17). Navigational bronchoscopy with or without the robotic platform can be used to label the vicinity of the lesion with dye such as methylene blue, indocyanine green, or contrast. Moreover, 3D models can be constructed to facilitate pre-operative planning (23).

Conclusions

This review highlighted the notable past studies on minimally invasive thoracoscopic management of pulmonary oligometastases from esophageal cancer. The main finding is that there are very few studies on the specific topic of pulmonary metastasectomy for esophageal cancer, and the prognosis heavily depends on patient selection. Based on these limited studies of small sample sizes, some general guidance can be applied when weighing the benefits versus risks of pulmonary matastasectomy. Across studies, short DFI and presence of extrapulmonary metastatic disease were found to be negative prognostic factors for survival. Therefore, in the presence of these negative prognostic factors, surgery may not be warranted. There is little direct comparison between thoracotomy vs. thoracoscopic approach based on these studies. The approach can be individualized based on tumor location, ease of tumor marking technology, and patient factors.

There remain several gaps in this field that future studies can target. Firstly, the current literature is predominantly from the Japanese population with SCC type of esophageal cancer. In contrast, AC is not as well studied. Secondly, there is a paucity of studies since 2019, despite the fact that patients are now living longer because of advent of adjuvant therapy. We are entering an exciting era where the median survival of patients with esophageal is rapidly improving. It is possible that with better immunotherapy, the distant recurrence patterns could change favorably, with more patients having oligometastases that are amenable to treatment with curative intent. Thirdly, new studies are needed to assess the role of new technology. The “Achilles heel” of using thoracoscopic approach has been the inability for bimanual palpation for hidden metastastases. However, advances in imaging and nodule marking technology have provided thoracoscopic approach with accurate pre-operative planning and intraoperative localization. Current technology of computed tomography and PET are very good at pre-operative detection of pulmonary metastases. The use of manual palpation in thoracotomy is unlikely to uncover metastases completely unseen on modern imaging modalities. Moreover, as intraoperative nodule marking techniques using various navigational bronchoscopy platforms mature, the thoracoscopic approach can locate and resect nodules that are not palpable from the surface. The same technology that allows endobronchial navigation to mark tumors can be developed to deliver ablation or brachytherapy. Future studies will need to evaluate and compare emerging and hybrid techniques. Lastly, we are hopeful that the widespread use of adjuvant immunotherapy may positively affect the cure rate and recurrence pattern in patients with esophageal cancer.

Acknowledgments

The authors express their deepest gratitude to Takashi Harano, MD (University of Southern California) for conception of this review.

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Anthony W. Kim and Takashi Harano) for the series “The Role of Minimally Invasive Approaches in the Pulmonary Oligometastases” published in Video-Assisted Thoracic Surgery. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-23-9/rc

Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-23-9/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-23-9/coif). The series “The Role of Minimally Invasive Approaches in the Pulmonary Oligometastases” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
2. Dresner SM, Griffin SM. Pattern of recurrence following radical oesophagectomy with two-field lymphadenectomy. Br J Surg 2000;87:1426-33. [Crossref] [PubMed]
3. Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol 2021;39:1995-2004. [Crossref] [PubMed]
4. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med 2021;384:1191-203. [Crossref] [PubMed]
5. Luketich JD, Alvelo-Rivera M, Buenaventura PO, et al. Minimally invasive esophagectomy: outcomes in 222 patients. Ann Surg 2003;238:486-94; discussion 494-5. [Crossref] [PubMed]
6. Nakagawa S, Kanda T, Kosugi S, et al. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg 2004;198:205-11. [Crossref] [PubMed]
7. Makowiec F, Baier P, Kulemann B, et al. Improved long-term survival after esophagectomy for esophageal cancer: influence of epidemiologic shift and neoadjuvant therapy. J Gastrointest Surg 2013;17:1193-201. [Crossref] [PubMed]
8. Treasure T. Oligometastatic cancer: an entity, a useful concept, or a therapeutic opportunity? J R Soc Med 2012;105:242-6. [Crossref] [PubMed]
9. Depypere L, Lerut T, Moons J, et al. Isolated local recurrence or solitary solid organ metastasis after esophagectomy for cancer is not the end of the road. Dis Esophagus 2017;30:1-8. [PubMed]
10. Ghaly G, Harrison S, Kamel MK, et al. Predictors of Survival After Treatment of Oligometastases After Esophagectomy. Ann Thorac Surg 2018;105:357-62. [Crossref] [PubMed]
11. Meng D, Fu L, Wang L, et al. Video-assisted thoracoscopic surgery versus open thoracotomy in pulmonary metastasectomy: a meta-analysis of observational studies. Interact Cardiovasc Thorac Surg 2016;22:200-6. [Crossref] [PubMed]
12. Mutsaerts EL, Zoetmulder FA, Meijer S, et al. Long term survival of thoracoscopic metastasectomy vs metastasectomy by thoracotomy in patients with a solitary pulmonary lesion. Eur J Surg Oncol 2002;28:864-8. [Crossref] [PubMed]
13. Rusidanmu A, Chin W, Xu J, et al. Does a thoracoscopic approach provide better outcomes for pulmonary metastases? J Thorac Dis 2021;13:2692-7. [Crossref] [PubMed]
14. Schizas D, Lazaridis II, Moris D, et al. The role of surgical treatment in isolated organ recurrence of esophageal cancer-a systematic review of the literature. World J Surg Oncol 2018;16:55. [Crossref] [PubMed]
15. Komatsu H, Izumi N, Tsukioka T, et al. Impact of Perioperative Chemotherapy on Prognosis of Patients with Esophageal Carcinoma Undergoing Pulmonary Metastasectomy. Ann Thorac Cardiovasc Surg 2019;25:253-9. [Crossref] [PubMed]
16. Seesing MFJ, van der Veen A, Brenkman HJF, et al. Resection of hepatic and pulmonary metastasis from metastatic esophageal and gastric cancer: a nationwide study. Dis Esophagus 2019;32:doz034. [Crossref] [PubMed]
17. Kobayashi N, Kohno T, Haruta S, et al. Pulmonary metastasectomy secondary to esophageal carcinoma: long-term survival and prognostic factors. Ann Surg Oncol 2014;21:S365-9. [Crossref] [PubMed]
18. Shiono S, Kawamura M, Sato T, et al. Disease-free interval length correlates to prognosis of patients who underwent metastasectomy for esophageal lung metastases. J Thorac Oncol 2008;3:1046-9. [Crossref] [PubMed]
19. Ichikawa H, Kosugi S, Nakagawa S, et al. Operative treatment for metachronous pulmonary metastasis from esophageal carcinoma. Surgery 2011;149:164-70. [Crossref] [PubMed]
20. Kozu Y, Oh S, Takamochi K, et al. Surgical outcomes of pulmonary metastases from esophageal carcinoma diagnosed by both pathological and clinical criteria. Surg Today 2015;45:1127-33. [Crossref] [PubMed]
21. Kanamori J, Aokage K, Hishida T, et al. The role of pulmonary resection in tumors metastatic from esophageal carcinoma. Jpn J Clin Oncol 2017;47:25-31. [Crossref] [PubMed]
22. Sánchez-Danés A, Blanpain C. Deciphering the cells of origin of squamous cell carcinomas. Nat Rev Cancer 2018;18:549-61. [Crossref] [PubMed]
23. Sarsam M, Peillon C, Baste JM. Robotic pulmonary metastasectomy using precision multimodal surgical navigation. J Vis Surg 2019;5:53. [Crossref]
24. Ercan S, Nichols FC 3rd, Trastek VF, et al. Prognostic significance of lymph node metastasis found during pulmonary metastasectomy for extrapulmonary carcinoma. Ann Thorac Surg 2004;77:1786-91. [Crossref] [PubMed]
25. Shiono S, Matsutani N, Okumura S, et al. The prognostic impact of lymph-node dissection on lobectomy for pulmonary metastasis. Eur J Cardiothorac Surg 2015;48:616-21; discussion 621. [Crossref] [PubMed]
26. Inoue T, Katoh N, Aoyama H, et al. Clinical outcomes of stereotactic brain and/or body radiotherapy for patients with oligometastatic lesions. Jpn J Clin Oncol 2010;40:788-94. [Crossref] [PubMed]
27. Kang JK, Kim MS, Kim JH, et al. Oligometastases confined one organ from colorectal cancer treated by SBRT. Clin Exp Metastasis 2010;27:273-8. [Crossref] [PubMed]
28. Tree AC, Khoo VS, Eeles RA, et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol 2013;14:e28-37. [Crossref] [PubMed]
29. Niibe Y, Yamamoto T, Onishi H, et al. Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients. Anticancer Res 2020;40:393-9. [Crossref] [PubMed]
30. Yamamoto T, Niibe Y, Matsumoto Y, et al. Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Esophageal Cancer: Results and Prognostic Factors. Anticancer Res 2020;40:2065-72. [Crossref] [PubMed]
31. Matsui Y, Hiraki T, Gobara H, et al. Percutaneous radiofrequency ablation for pulmonary metastases from esophageal cancer: retrospective evaluation of 21 patients. J Vasc Interv Radiol 2014;25:1566-72. [Crossref] [PubMed]
32. Cerfolio RJ, Bryant AS, McCarty TP, et al. A prospective study to determine the incidence of non-imaged malignant pulmonary nodules in patients who undergo metastasectomy by thoracotomy with lung palpation. Ann Thorac Surg 2011;91:1696-700; discussion 1700-1. [Crossref] [PubMed]
33. Mutsaerts EL, Zoetmulder FA, Meijer S, et al. Outcome of thoracoscopic pulmonary metastasectomy evaluated by confirmatory thoracotomy. Ann Thorac Surg 2001;72:230-3. [Crossref] [PubMed]
34. Eckardt J, Licht PB. Thoracoscopic versus open pulmonary metastasectomy: a prospective, sequentially controlled study. Chest 2012;142:1598-602. [Crossref] [PubMed]