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Eur J Cardiothorac Surg 2004;25:151-154
© 2004 Elsevier Science NL

Staged pulmonary and hepatic metastasectomy in colorectal cancer—is it worth it?

^a Department of Thoracic Surgery, Leeds General Infirmary, D Floor, Jubilee Building, Great George Street, Leeds LS1 3EX, UK
^b Department of Hepatobiliary Centre, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK

Received 8 May 2003; received in revised form 11 November 2003; accepted 17 November 2003.

^* Corresponding author. Tel.: +44-113-3925-737; fax: +44-113-3926-657
e-mail: thorpyat{at}aol.com

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

 
Objective: Resection of isolated pulmonary and hepatic metastases from colorectal cancer can offer potential cure. However, little data is available to determine the results of staged hepatic and pulmonary resections in the same patient. Methods: We retrospectively reviewed all patients who underwent staged hepatic and pulmonary metastasectomy for colorectal cancer in our institute from September 1998 to May 2002. Probability of survival was estimated by the Kaplan–Meier method. Results. Thirty-three metastasectomies (seven redo) were carried out in 26 patients. There were 19 male and 7 female patients with a mean age of 61 years (range 34–76 years). The mean disease-free interval for hepatic and pulmonary resection was 21.8 and 23.9 months, respectively. Sternotomy, thoracotomy and video assisted thoracoscopic approach were used in 3.03, 72.7 and 24.2% of patients, respectively. Wedge excision, lobectomy and pneumonectomy were carried out in 87.87, 9.09 and 3.03% of cases, respectively. There was one hospital death following acute respiratory failure after pneumonectomy. Mean follow-up was 23.3 months (range 2–71 months). The mean survival after last pulmonary resection was 34.7 months (SE 3.03 and 95% CI of 28.8–40.6). Conclusion: Our results support aggressive surgical management of pulmonary and hepatic metastases in colorectal cancer.

Key Words: Metastasectomy • Colorectal cancer VATS • Lung resection • Lung metastases • Hepatic metastases

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

 
Conventional management of metastatic colorectal cancer using 5-fluorouracil (5-FU) based chemotherapy seldom produces long-term survival. In search of more effective treatment, emphasis has shifted to surgical intervention [1–3]. Hepatic resection for colorectal liver metastases is a well-accepted treatment modality [4,5].

There are several reports regarding survival following staged resection of colorectal metastases to both liver and lung [6–8]. These studies showed prolonged survival in comparison with alternative therapies. However, they were limited by a small cohort of patients [9,10]. Reported 5-year survival was 30–55% [6,7].

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

 
We performed a retrospective analysis of all patients who underwent staged hepatic and pulmonary resection for colorectal metastases from September 1998 to May 2002. All patients had either synchronous or metachronous lesions in liver and lung. There was no evidence of primary or metastatic disease elsewhere at the time of resection. Synchronous lesions were defined as those identified simultaneously, in the liver and lung, at the time of single investigation either on computer tomography (CT) scan or magnetic resonance imaging (MRI) of the chest and abdomen. Metachronous lesions were defined as those metastases identified in either the lung or liver on follow-up after removal of the primary colonic lesion. Only patients who underwent liver resection prior to pulmonary resection were included. The medical records of all patients were reviewed to collect the demographic details including Dukes stage of colorectal cancer, type of pulmonary and hepatic resection, morbidity, mortality, adjuvant therapy and survival.

Hepatic resections were defined as solitary wedge resections, segmentectomies (single or multiple) and lobectomies or extended lobectomies. Follow-up after hepatic resection was at 6 weeks, 3, 6 months and annual intervals. This consisted of a CT scan of the chest, abdomen, pelvis and MRI scan of the liver. In addition, plasma CEA levels were monitored. Pulmonary resections were defined as wedge resection (single or multiple), lobectomy or pneumonectomy. Median sternotomy or sequential thoracotomies were used for patients with bilateral metastases, video assisted thoracoscopic approach (VATS) for solitary peripheral metastases and thoracotomy for unilateral multiple metastases, bulky disease and redo metastasectomy. Systematic lymph node dissection (SLND) was performed according to the operating surgeon's judgment. Mortality after lung resection was defined as death within 30 days after lung resection.

Probability of survival was estimated by the Kaplan–Meier method. Survival was estimated from the time of the last pulmonary resection. Following 6 week post-operative follow-up in the thoracic surgical outpatient clinic, patients were followed up at three monthly intervals for the first year.

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

 
There were 26 patients (male:female=19:7) with a mean age of 61 years (range 34–76 years). The mean interval from colonic to hepatic resection and from hepatic to pulmonary resection was 21.8 (0–132) and 23.9 (1–85) months, respectively. For seven patients who underwent multiple pulmonary metastasectomies, the disease-free interval was defined as the time between the hepatic resection to the first pulmonary resection. The mean interval in them was 45.5 (2–157) months. The Dukes stage of primary colorectal cancer was A in 3 (11.5%), B in 9 (34.6%), C in 13 (50.0%) and D in 1 (3.8%) patients. There were 19 (73.0%) patients with rectal cancers and 7 (26.9%) with colonic cancers.

A total of 33 pulmonary metastasectomies were performed. This included seven redo procedures. There was 1 pneumonectomy, 3 lobectomies and 29 single or multiple wedge excisions. Pneumonectomy was indicated for large central metastases. All lung lesions were confirmed to be metastases on histopathology. An average of 1.3 metastases has been resected with each procedure and 1.7 (range 1–6) metastases have been resected in each patient. All but one patient had complete resection of disease on pathological examination of the specimen. There were two patients with positive hilar nodes (N1) on systematic lymph node sampling.

There were five patients’ synchronous metastases. In all of them staged resection was performed with hepatic resection first. Hepatic resections included extended lobectomy (right 1, left 2), anatomical segmentectomy in nine patients (1–4 segment each patient) and non-anatomical wedge excision or metastasectomy in 13 patients. An average of 1.4 (range 1–5) metastases has been resected at the time of hepatic resection. One patient underwent liver transplantation for multiple hepatic metastases and subsequently underwent lung metastasectomy.

Adjuvant therapy consisting of 5-fluorouracil based chemotherapy was administered in 13 (50.0%) patients after colorectal resection, 21 (80.7%) and 22 (84.6%) patients after hepatic and pulmonary resection, respectively. Three patients had pelvic irradiation as neoadjuvant treatment for primary rectal cancer. Another two patients received pelvic irradiation after colorectal surgery. The pre-thoracotomy CEA level was available in only 20 patients and was greater than 5 ng/ml in seven patients.

There was one death on the eighth post-operative day from acute respiratory distress syndrome secondary to a left pneumonectomy. There was no morbidity in the remaining 25 patients. Follow-up ranged from 2 to 71 months with a mean period of 20.2 months. The mean survival after last pulmonary resection (Fig. 1) was 34.7 months (SE 3.03 and 95% CI of 28.8–40.6).

View larger version (9K): [in this window] [in a new window]   Fig. 1. Actuarial survival calculated by Kaplan–Meier method from the last pulmonary resection.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

The liver and lung are the most common sites of distant metastases for colorectal cancer. Occasionally, these are limited only to the liver or the lung. From this subset of patients a highly selected group will emerge in whom curative resection can be achieved. The aim of surgery in this group of patients is to prolong survival. Smith et al. reported a 5-year survival of 52% [9]. Gough et al. have reported median survival of 27 months after completion of liver and lung surgery [10].

The number of metastases did not influence survival in our series [3,11,12]. This contradicts results from other studies [1,2,7]. We have used VATS wedge excision in 8 (23.6%) procedures and achieved complete resection in all of them. It is increasingly accepted that VATS is an attractive approach in small solitary peripheral lesions, without compromising long-term survival [6,13,14]. Both hepatobiliary and thoracic surgical teams evaluated patients with synchronous lesions and the hepatic lesion was approached first. The staged resection was to ensure that R0 (hepatic) resection could be achieved.

SLND may have an impact on a patient's survival and disease-free survival as well as influencing the decision as to whether adjuvant therapy should be administered or not. However, the role of SLND has not been adequately explored in the management of pulmonary metastases. To answer the question as to whether or SLND should be routine at pulmonary metastasectomy, Loehe and associates conducted a prospective analysis of 63 patients who underwent 71 resections [15]. In their series nine patients out of 63 (14.2%) were found to have mediastinal lymph nodes that contained malignant cells. This represents a significant number of patients who are otherwise assumed to be free of residual tumour [15]. They conclude that routine mediastinal SLND at the time of pulmonary metastasectomy should be performed. Knowledge regarding a patient's mediastinal lymph node status may strongly influence the decision for subsequent adjuvant therapy. Furthermore, it has been shown that local recurrence following pulmonary metastasectomy is reduced if SLND is performed [16].

Robinson et al. compared survival among 25 patients who underwent resection of hepatic and pulmonary metastases with a similar group (23 patients) treated conservatively [8]. The reported 5-year survival following surgical resection was 43% (median 47 months) compared to 0% (median 7 months) in the non-resection group. Risk factors included old age, multiple liver metastases and a short disease-free interval.

These authors have also stated that metachronous resections survived longer (median survival 70 months) than the synchronous group (median survival 22 months). Survival was calculated from time of colorectal surgery. In our study we did not detect any survival difference amongst these groups. Our mean survival was 34.7 months from the time of last pulmonary resection, which compares favourably with other studies of a similar nature [6–8].

In synchronous metastases spread through the portal venous system to liver and systemic venous system to the lungs appears to occur at the same time. In metachronous metastases spread is probably systemic, from colorectal primary through the portal system to the liver and then via the systemic venous system to reach the lungs.

Kobayashi et al. compared the survival between a hepatic and pulmonary resection group and another group consisting of patients who underwent pulmonary resection but had no evidence of hepatic metastases [7]. No significant difference in survival among these groups was found. The 3-, 5- and 8-year survival amongst combined resection versus pulmonary resection was 36, 31 and 23% versus 56, 40 and 28%, respectively. The encouraging results reported by the various surgical teams may be accounted for by an aggressive surgical approach. In our study, the majority of patients had metachronous metastases. This may be one of the reasons for good survival although there was no statistically significant difference among the synchronous and metachronous metastases patients. This may due to a small number of patients in the synchronous group.

	5. Conclusion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

 
In the absence of effective alternative therapy, every fit patient with pulmonary and hepatic metastases should be considered a surgical candidate providing complete resection could be achieved. Such an aggressive approach in a specialist unit is safe and offers the best chance for long-term survival.

	Footnotes

 
Presented at the 10th Annual Meeting of the European Society of Thoracic Surgeons, Istanbul, Turkey, October 26--28, 2002.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusion References

 

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