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Ann Thorac Surg 2001;71:975-980
© 2001 The Society of Thoracic Surgeons
a Division of General Thoracic Surgery, Mayo Foundation, Rochester, Minnesota, USA
b Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, Minnesota, USA
Address reprint requests to Dr Miller, Mayo Medical Center, 200 First St, SW, Rochester, MN 55905
e-mail: miller.danielmd{at}mayo.edu
Presented at the Thirty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.
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Abstract |
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Methods. We reviewed the records of all patients who underwent surgical resection of both hepatic and pulmonary metastases from colorectal cancer between 1980 and 1998.
Results. A total of 58 patients underwent resection of both hepatic and pulmonary metastases secondary to colorectal cancer. All patients had local control of their primary cancer before metastasectomy. There were no operative deaths. Morbidity occurred in 12% of patients. Follow-up was complete in all patients, with a median duration of 62 months (range, 6 to 201 months). The 5- and 10-year survivals were 30% and 16%, respectively. A premetastasectomy carcinoembryonic antigen level greater than 5 ng/mL increased the risk of early death (p = 0.029). Neither the number of pulmonary lesions nor the time interval between the primary surgery and the metastasectomy had a significant impact on survival (p = 0.67). At 5 years, 55% of patients were free of disease. Four patients had lymph node involvement at the time of pulmonary resection and all 4 patients died within 22 months of their pulmonary metastasectomy.
Conclusions. Resection of both hepatic and pulmonary metastases secondary to colorectal cancer in highly selected patients is safe and results in long-term survival. Thoracic lymph node involvement and elevated carcinoembryonic antigen levels before pulmonary metastasectomy are associated with reduced survival.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionReferences |
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Conventional management of metastatic colorectal cancer has largely been directed at palliation. Chemotherapy using a fluorouracil (5-FU)–based treatment regimen is considered to be the standard treatment but seldom produces long-term survival. Because of this, surgical resection for isolated pulmonary or hepatic metastases has been advocated, with encouraging results in highly selected patients. Resection of isolated hepatic metastases has yielded 5-year survival rates ranging from 25% to 42% [5–6]. Resection of isolated pulmonary metastases has yielded similar 5-year survival rates ranging from 21% to 43% [2, 5, 7–10].
These encouraging results have expanded the indications for resection of colorectal metastases to patients with both hepatic and pulmonary disease. Initial reports from other institutions are encouraging but are limited by small numbers of patients [5, 11–16]. We reviewed our experience with this highly select group of patients to determine the efficacy of surgical resection of both hepatic and pulmonary metastases from colorectal cancer.
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Material and methods |
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TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionReferences |
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Liver resections were classified as solitary wedge resection, multiple wedge resection, lobectomy, or trisegmentectomy. Pulmonary resections were classified as solitary wedge resection, multiple wedge resection, or lobectomy.
The medical records were reviewed to determine such variables as age, sex, prethoracotomy carcinoembryonic antigen (CEA) level, type and extent of resection, number of metastatic lesions, presence of tumor cells in thoracic lymph nodes, administration of adjuvant chemotherapy or radiation therapy, tumor-free interval, morbidity, and mortality. The CEA levels were considered to be abnormal if they exceeded 5 ng/mL. Thoracic lymph nodes were classified according to the International System for Staging Lung Cancer [18]. Minor complications including superficial wound infections, atrial fibrillation, and atelectasis were not included in the morbidity analysis. Operative mortality was any death that occurred within 30 days of either the liver or lung operation or during the same hospitalization. Follow-up data were obtained through routine surveillance office visits, letter surveys, or telephone documentation.
Survival was estimated using the Kaplan-Meier method [19]. Survival curves were compared with log rank tests. The effect of continuous variables on survival was evaluated with the Cox proportional hazards model [20]. Statistical significance was set at p less than 0.05.
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Results |
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TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionReferences |
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All patients had initial colorectal resections. The timing and sequence of the hepatic and pulmonary resections varied. A total of 45 patients had the liver resection first, followed by lung resection. Seven patients had pulmonary resections before the liver resection. Six patients had the lung and liver resection during the same procedure. Four patients had their colorectal, liver, and lung resections performed within 3 months and were considered to have synchronous metastases. None of these 4 patients survived 5 years.
Median age at the time of liver resection was 61 years (range, 31 to 83 years). Median time from colorectal resection to liver metastases was 1.3 years (range, 0 to 14.7 years). In all, 33 patients (57%) had solitary lesions, 10 (17%) had two metastatic lesions, 3 (5%) had three, and 2 (3%) had four. Ten patients (17%) had multiple lesions but data were incomplete in determining the exact number. A total of 25 patients (43%) underwent hepatic wedge resections, 12 (21%) had lobectomy, 20 (34%) had trisegmentectomy, and 1 patient (2%) had multiple liver wedge resections. In addition, 10 patients (17%) underwent repeat liver resections for recurrent disease at a median of 1.1 years (range, 0 to 8.5 years).
Median age at the time of lung resection was 63 years (range, 31 to 85 years). The median time from colorectal resection to the presentation of lung metastases was 3.2 years (range, 0 to 8.5 years). A total of 31 patients (53%) had a solitary lesion, 13 (22%) had two, 10 (17%) had three, and 4 (7%) had four lesions. In all, 52 patients (90%) had their resection performed through a thoracotomy, 3 (5%) underwent video-assisted thoracic surgery, and 3 (5%) had a clam-shell incision. A total of 20 patients (52%) had wedge resection, 6 (10%) had lobectomy, and 22 (38%) had multiple wedge resections. Four patients had thoracic lymph node metastasis. Two had N1 lymph node metastases and two had N2 lymph node involvement. A total of 16 patients (28%) underwent repeat pulmonary resections for recurrent disease at a median of 0.6 years (range, 4 days to 2.6 years) from the first lung operation.
There were no operative deaths. Postoperative complications occurred in 7 (12%) patients (Table 1). Follow-up was complete in all patients and ranged from 6 to 201 months, with a median of 62 months.
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionReferences |
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Pulmonary resection for metastatic colorectal cancer was first performed by Blalock [21] in 1944. In 1992, we reported our experience with 139 consecutive patients who underwent pulmonary resections for metastatic colon cancer with no operative deaths. Overall 5- and 20-year survival was 30.5% and 16.2%, respectively [9]. Other institutions have also reported similar 5-year survivals ranging from 21% to 43% [2, 5, 7–10]. Surgical resection of isolated hepatic metastases has also resulted in 5-year survivals ranging from 25% to 42% with acceptable operative mortality of 4% [5–6].
Limiting surgical resection to patients with single-organ metastases may be denying some patients a chance for long-term survival; consequently we extended our indications to some highly selected patients with both hepatic and pulmonary metastases. Small retrospective studies have reported encouraging 5-year survival rates ranging from 11% to 52% [5, 11–16]. Our 5-year survival of 30% compares favorably with these series.
The small number of patients in most series has limited identifying patients who are likely to benefit from surgical resection. Prognostic variables such as prethoracotomy CEA level, age, number of metastatic lesions, disease-free interval, and synchronous versus metachronous lesions have all been identified as affecting survival [5, 11, 12, 14, 16, 22, 23]. None, however, have been determined to be absolute contraindications to surgical resection.
We identified elevated prethoracotomy CEA levels and thoracic lymph node metastasis as the only variables associated with a significant decrease in survival. Serum CEA level is an indication of the total tumor mass and the ability of tumor cells to express CEA. This antigen is known to participate in intracellular recognition as well as promotion of adhesion of tumor cells to host cells, possibly explaining the decreased survival [5].
One possible contraindication to surgical resection is the presence of lymph node metastasis within the chest. We identified 4 patients in our series that had positive thoracic lymph nodes. Follow-up of these patients revealed limited survival. Although a trend toward decreased survival with short disease-free intervals was observed, this relationship was not statistically significant. Neither the number of pulmonary nodules resected nor the method of resection had a significant relationship to the outcome.
Before surgical resection of metastatic pulmonary lesions, a thorough evaluation is indicated to look for other sites of metastatic disease. Bone scan and computed tomography of the head should be included in any patient with symptoms. Computed tomography of the chest and abdomen are important in identifying lymphadenopathy or abdominal recurrence. Patients with suspected mediastinal disease should undergo mediastinoscopy or mediastinotomy before undergoing surgical resection. A barium enema or colonoscopy should also be included to rule out local recurrence or metachronous lesions within the colon. Patients who present with both hepatic and pulmonary metastases should undergo staged resections beginning with the organ with the most difficult lesion to resect first. If a complete resection is performed, the patient should undergo resection of the other organ system when they have recovered from the first operation. Simultaneous resections occasionally can be performed in select patients who are in good health and who require limited hepatic and pulmonary resections.
The surgical approach to resecting pulmonary lesions does not appear to affect survival. We used a standard posterolateral thoracotomy in the majority of patients. In many situations, additional pulmonary lesions are discovered at the time of thoracotomy that were not identified with a preoperative computed tomographic scan [24]. Some of these lesions may be missed using a thorascopic approach [25]; therefore, we recommend an open approach for metastasectomy in this group of patients. Metastatic lesions should be resected with negative margins while limiting the amount of normal lung parenchyma removed, allowing for possible repeat resections. This approach is in contrast to traditional lung cancer operations in which anatomical resections are performed. In addition to resecting metastatic lesions, thoracic lymph node sampling should be performed for prognostic indications
In most series, a small number of patients have undergone repeat lung resections for recurrent disease with low mortality and improved survival. Of our patients, 16 underwent additional pulmonary resections for recurrent disease with no mortality. Although this was a highly select group, their 43% rate of 5-year survival was encouraging. These findings are analogous to repeat hepatic resections for metastatic colorectal cancer. The percentage of patients salvaged remains constant at nearly 25% after each resection [26].
We conclude that resection of hepatic and pulmonary metastasis secondary to colon cancer is safe and results in long-term survival. Thoracic lymph node metastasis and elevated CEA levels are associated with reduced survival.
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Discussion |
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DR HEADRICK: To answer your first question, three-fourths of the patients in the series had lymph node dissections, and this represents a comparison between the experience in the early years where it was not routinely performed, and in situations where there were 3 patients who underwent thoracoscopy and lymph node dissection was not performed in those patient. The rest of the patients had either sampling or a complete lymphadenectomy, which is not part of our standard routine, certainly in the last half of the series. So the majority of the patients did have lymph node dissection, and we certainly advocate it at this point. The mode of death in all the patients was recurrence through a cancer. Usually it represented a local recurrence within the abdomen and the liver. Sometimes it was also associated with recurrent lesions in the lung. But it was usually a multifactorial process. I think I answered all of your questions.
DR NGUYEN: The reason I mentioned my curiosity about the mode of recurrence is that there is now an ongoing randomized trial at the National Cancer Institute evaluating Thalidomide as an anti-angiogenic agent, in an adjuvant setting, to prevent recurrence of metastasis from macroscopic deposits after complete resection of liver or lung macroscopic metastasis from colon cancer.
DR TIMOTHY M. ANDERSON (Buffalo, NY): In patients who present with simultaneous liver and lung metastases, how do you prioritize which resection would come first?
DR HEADRICK: Our approach has been to take the most difficult resection first. Usually that’s the liver resection. The whole advantage or ability to give these patients long-term survival depends on complete resection of both the lesions. And sometimes you approach the liver resection and you may find disease within the pleural cavity or in the abdomen that wasn’t recognized, and in those situations these patients fall out of our combined approach. If the liver resection is successful and there is no evidence of disease, then once they recover from the operation, we proceed on with the lung resection.
DR MILTON SAUTE (Haifa, Israel): You presented here patients with no more than four metastases. Do you consider a greater number of metastases a contraindication for surgery?
DR HEADRICK: No, we would not. I think that the two main considerations for surgery primarily involve that there is not resectable disease elsewhere and that, along the process at each stage, you are able to completely resect the disease. I think what happens in our series is that the people who may have had even more lesions, either pulmonary or hepatic, maybe somewhere along the line fell out of the series by having too advanced disease or recurrence of a disease that prevents them from getting the second resection.
DR FREDERIC W. GRANNIS, JR (Duarte, CA): I frequently get calls from my surgical oncology colleagues who are getting much more aggressive in the treatment of colorectal/liver metastases, including perfusions of hepatic artery and portal vein with chemotherapy, cryotherapy, and other physical therapies when they cannot achieve complete resection of liver metastases. Are such patients reflected in this group of patients?
The second question is, we now have better ways to make sure that there are no other metastases, including CEA scans, other immunoscans, and PET scans. Have you used those modalities in this series of patients?
DR HEADRICK: None of the patients reflected any of the intrahepatic infusions. They were purely a highly select group in which at both stages, at the liver and the lung, they had resectable lesions, and that was the mode of therapy.
As far as any other scanning, the main modalities for looking for recurrence in this group were primarily restricted to CT scans of the chest and the abdomen. So we haven’t utilized any other advanced scanning techniques, at least in this series.
DR ALLEN J. TOGUT (Wilkes-Barre, PA): Why did you get in trouble with the chyle leak and how did you deal with it?
DR HEADRICK: The chyle leak was presumed to be caused from the lymph node dissection in the mediastinum. It was treated conservatively. The patient was placed on no oral intake, on central nutrition, and it resolved over the course of his hospitalization and did not require reexploration.
DR PETER GOLDSTRAW (London, England): One intuitively feels that, with metastasis at two sites, the patient’s prognosis must be worse than for those with metastasis at one site. Have you compared your survival with colon patients having only liver metastasectomy and only lung metastasectomy?
DR HEADRICK: In the early 1990s we published a series looking at just lung metastasis from colon cancer, and the survival was remarkably similar to what we found in this group; 5 years, about 30%. It seems like if you isolate liver or pulmonary metastases, you can probably quote a number between 20% and 40% and be safe. And that’s going to be their predicted 5-year survival, assuming there is no other widespread disease and that what metastasis is present you can completely resect.
DR DOUGLAS E. WOOD (Seattle, WA): Doctor Headrick I was a little surprised to see that the disease-free interval did not select out as an important factor in survival, and then you had a later slide that showed that those who had a very short disease-free interval actually had poorer survival. Why do you think the disease-free interval did not show itself statistically to be a factor in this series? And could you leave us with what criteria we ought to use to select patients for combined hepatic and pulmonary resections for colorectal cancer?
DR HEADRICK: The disease-free interval wasn’t statistically significant, but there was a correlation between the longer they were out from the original colon cancer and the longer that disease-free interval was, there was a relationship; but it just didn’t approach statistical significance. I think part of that was related to the way this group was selected as well as the numbers. Maybe if the patient group had been larger, we might have been able to determine a significance. Other series, although small, have shown that that is a factor. We just were not able to reproduce it.
I think that, as far as combined resections, if you have a liver procedure that is not going to be very extensive and maybe there is a solitary pulmonary nodule that is also easily resected in a healthy patient, then a combined approach in our case certainly does not incur any mortality or morbidity. I think for more complex resections they ought to be staged and done at separate times.
DR RUSSEL R. KRAEGER (St. Louis, MO): I was wondering if you have these data. The people who presented with simultaneous liver and pulmonary metastases found at the same time, do they do worse than the people who show up with isolated liver or isolated lung followed by the other?
DR HEADRICK: Only if the metachronous lesions, both the lung and the liver lesions, presented within 3 months of that colon resection. Presumably they may have already been there at the time of the initial operation and represented metachronous lesions in a stage IV patient. In our group it did not become a statistically significant difference in their survival, but mainly because most of them were further out and maybe it represented just a more biologically favorable tumor in those patients.
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