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The optimal timing to resect pulmonary metastasis

Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan

Received 27 September 2007; received in revised form 26 February 2008; accepted 4 March 2008.

^_* Corresponding author. Tel.: +81 78 382 5942; fax: +81 78 382 5959. (Email: maniwa{at}med.kobe-u.ac.jp).

	Abstract

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

 
Objective: There is no criterion for the timing of surgical resection of pulmonary metastasis. In this study, we investigated the optimal period for pulmonary metastasectomy. Methods: Between 2000 and 2005, 68 patients underwent complete pulmonary resection of metastatic cancer. Clinical prognostic factor in multivariate analysis was examined. Results: The interval from pulmonary metastasectomy until subsequent recurrence and the interval from detection of pulmonary metastasis until pulmonary metastasectomy were independent prognostic factors. To investigate the relationship between the two characteristics, the 68 patients were divided into two groups according to the interval from lung metastasectomy until subsequent recurrence. Nineteen patients relapsed within 1 year after pulmonary metastasectomy (group A), while 49 patients did not relapse within 1 year (group B). The interval from detection of pulmonary metastasis until pulmonary metastasectomy was significantly shorter in group A than in group B (2.9 months vs 7.1 months, p = 0.01). Based on these results, we divided the patients into two different groups and survival was compared. Significantly shorter survival was observed in the patients who underwent pulmonary metastasectomy within 3 months after detection of pulmonary metastasis (group X, n = 35) than in those who underwent the surgery beyond 3 months (group Y, n = 33). Conclusions: There were many cases of early relapse after metastasectomy when the interval from detection of pulmonary metastasis until pulmonary metastasectomy was short. Performing metastasectomy at least three months after detection of pulmonary metastasis may significantly improve the prognosis of patients.

Key Words: Pulmonary metastasis • Metastasectomy • Opportunity for pulmonary resection

	1. Introduction

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

 
Pulmonary metastasectomy has been widely adopted for the treatment of patients with isolated pulmonary metastasis. Several reports demonstrated that resection improves the prognosis of patients with pulmonary metastasis [1,2]. Moreover, pulmonary metastasectomy has been aggressively performed for resection of multiple or bilateral lesions [3–5]. However, early relapse after resection of pulmonary metastasis has often been encountered when the interval from detection of pulmonary metastasis until pulmonary metastasectomy was short. In the present study, we analyzed the optimal timing for resection of pulmonary metastasis.

	2. Patients and methods

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

 
This retrospective study included 68 patients who underwent curative pulmonary resection for metastatic lung tumor in our department between August 2000 and November 2005. In complete resection, all known pulmonary nodules which were detected by preoperative computed tomography (CT) and intraoperative palpation were removed during thoracotomy. Patients who underwent pulmonary biopsy were excluded. Table 1 shows the sites of the primary tumors of the 68 patients. Regarding the pulmonary metastases, solitary lesions were detected in 53 patients, multiple unilateral lesions in five patients and bilateral lesions in 10 patients.

Statistical analyses were carried out with StatView software (version 5; SAS Institute, Inc., Cary, NC). Univariate statistical analyses including Student's t-test, Mann–Whitney U-test and ²-test were performed. Multivariate analysis was performed according to the Cox proportional hazards model. Survival which was defined as the interval from pulmonary metastasectomy until death or the date of last follow-up was analyzed by the Kaplan–Meier method [6], and differences in their distributions were evaluated by the log-rank test. Analysis was regarded as statistically significant at a probability value less than 0.05.

	3. Results

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

 
The 68 patients who underwent pulmonary metastasectomy consisted of 46 males and 22 females. The patients’ ages ranged from 3 to 82 years, with a mean age of 59.5 years. The mean DFI was 32.9 ± 5.3 (standard error: SE) months (range, 0–284 months) and the mean interval from detection of pulmonary metastasis until pulmonary metastasectomy was 5.9 ± 1.0 (SE) months (range, 0–25 months). Regarding the pulmonary metastasectomy, wedge resection was performed in 53 patients, segmental resection in five patients, and lobectomy in 10 patients. The overall 1-year, 3-year and 5-year survival rates after pulmonary metastasectomy were 91.2%, 75.7% and 75.7%, respectively (Fig. 1 ).

View larger version (6K): [in this window] [in a new window]   Fig. 1. Overall survival curve of patients who underwent pulmonary metastasectomy.

View larger version (7K): [in this window] [in a new window]   Fig. 2. Survival curves of patients who underwent pulmonary metastasectomy within 3 months after detection of pulmonary metastasis (group X) and patients who underwent pulmonary metastasectomy beyond 3 months after detection of pulmonary metastasis (group Y). Significantly longer survival was observed in group Y than in group X (p = 0.02).

	4. Discussion

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

Recently, there have been many reports on indications and prognostic factors for resection of pulmonary metastasis. In the majority of reports, the indications and prognostic factors were analyzed by the primary organ such as the colorectum [7–11], uterus [12], and kidney [13], or by the disease such as malignant fibrous histiocytoma [14] and malignant melanoma [15]. Tumor markers, DFI, number of metastases and histologic type were analyzed, but the interval from detection of pulmonary metastasis until pulmonary metastasectomy was not discussed.

Maniwa et al. [16] reported that the prognosis was poor in patients with recurrent metastatic lung lesions after pulmonary metastasectomy, and it was especially poor in patients who developed them within 6 months. The results concerning multivariate analysis in this study was consistent with their report. In fact, the interval from pulmonary metastasectomy until subsequent recurrence was associated with prognosis. Furthermore, early relapse after pulmonary resection was associated with a short interval from detection of pulmonary metastasis until pulmonary metastasectomy in the present study.

Clarifying the mechanism of early relapse after pulmonary metastasectomy is extremely important for improving the results of surgery in patients with metastatic lung tumors. During surgery for metastatic lung tumors, we resected all macroscopic lesions that had been found by preoperative diagnostic imaging and intraoperative palpation. It was highly unlikely that tumor cells newly migrated to various organs and proliferated immediately after pulmonary metastasectomy. Relapse might be caused by the existence of pulmonary or extrapulmonary micrometastases that we could not detect before and during pulmonary metastasectomy [16]. In almost all cases in group X, re-evaluation of metastases was not performed prior to metastasectomy because the interval from detection of pulmonary metastasis until pulmonary metastasectomy was short. No re-evaluation might lead to overlooking a dormant metastasis. Expressed in another way, there might be some patients who develop additional metastatic lesions during interval from detection of pulmonary metastasis until pulmonary metastasectomy and were excluded from surgical candidates. Our results suggest that if pulmonary metastasis is detected, a fixed period of clinical follow-up and re-evaluation are necessary before pulmonary metastasectomy is performed.

With respect to imaging examinations, computed tomography (CT) scan, ultrasound, scintigram and/or magnetic resonance imaging (MRI) was used in most of our patients. It is also important to add more effective examinations. Pastorino et al. [17] demonstrated that metastases were detected by positron emission tomography (PET) which had a sensitivity and accuracy greater than those of contrast CT scan, and PET detection of occult distant metastases or recurrence at the primary site avoided unnecessary lung resections. We should perform re-evaluation of metastases using these devices before pulmonary surgery.

In this study, we performed pulmonary metastasectomy soon after the request from doctors who examined the patients at regular intervals. The difference of the interval from detection of pulmonary metastasis until pulmonary metastasectomy depended on the timing of doctors’ consultations. Besides, we stated that the two groups, X and Y, were no different in regards to gender, age, DFI, number of metastasis, and site of primary origin. However, the patients were not randomized and the primary tumor was found in various organs. Prospective trials should be undertaken in patients with primary tumors in limited sets of organs to confirm our findings.

	5. Conclusion

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

 
Our results suggest that in patients with pulmonary metastasis, clinical follow-up and re-evaluation for at least three months prior to metastasectomy would improve the prognosis of patients.

	References

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

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yutaka Okita Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanaka, Y. Articles by Okita, Y. Search for Related Content PubMed PubMed Citation Articles by Tanaka, Y. Articles by Okita, Y. Related Collections Lung - cancer