Is the mediastinal lymphadenectomy during pulmonary metastasectomy of colorectal cancer necessary?

doi:10.1510/icvts.2009.213173 Interactive CardioVascular and Thoracic Surgery 10 (2010) 694 699 Institutional report - Thoracic oncologic Is the mediastinal lymphadenectomy during pulmonary metastasectomy of colorectal cancer necessary? www.icvts.org a, b a a a b Tamas Szöke *, Ariane Kortner, Rainer Neu, Christian Grosser, Zsolt Sziklavari, Karsten Wiebe, Hans-Stefan Hofmann a,b a Department of Thoracic Surgery, Centre of Thoracic Surgery Regensburg, Krankenhaus Barmherzige Brüder, Prüfeninger Str 86, D-93049 Regensburg, Germany b Division of Thoracic Surgery, Centre of Thoracic Surgery Regensburg, University Regensburg, Regensburg, Germany Received 29 May 2009; received in revised form 2 February 2010; accepted 3 February 2010 Abstract The aim of study was to investigate the pattern of mediastinal lymph node metastases in patients with colorectal cancer metastasis. Twenty-four pulmonary metastasectomies with mediastinal lymphadenectomies were performed on 19 patients (14 unilateral and five bilateral operations). The metastases were centrally localised in eight cases; the primary tumour was colon cancer in 15 patients and rectal cancer in nine cases. The number and the localisation of metastases were recorded, as the clinico-pathological data of the primary tumours. The results were compared with the pattern of metastases in mediastinal lymph nodes. The data were subjected to statistical 2 processing with the x -test and Mann Whitney test. Mediastinal lymph node metastases were confirmed in eight cases (33.3%). The proportion of positive lymph nodes was significantly higher for central metastases (62.5% vs. 18.8%, Ps0.032). When the pathological stage of the primary tumour was more advanced, the proportion of lymph node metastases displayed a statistically not significant increase. The pattern of lymph node metastases did not correlate with the localisation of the lung metastases, disease-free interval and the diameter of the greatest pulmonary metastasis. The frequency of lymph node metastasis is relatively high, therefore, mediastinal lymphadenectomy during the resection of colorectal cancer metastases is necessary. 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Colorectal cancer; Mediastinal lymph node metastasis; Lymph node dissection 1. Introduction Colorectal cancer is one of the most frequent malignancies in developed countries. It has been estimated that in the EU, 217,000 new cases of colon cancer were diagnosed and )107,000 patients died of the disease in 2006 w1x. Approximately 10% of patients with colorectal cancer develop pulmonary metastases, although only 2% 4% of all patients have metastases limited exclusively to the lung w2x. An assessment of 5206 cases in the International Registry of Lung Metastases showed that lung metastasectomy in general is a safe and potentially curative procedure w3x. Although the types and techniques of metastasis resections are well described, the necessity of mediastinal lymphadenectomy and the prognostic role of mediastinal nodal involvement remain controversial w4, 5x. The aim of our retrospective study was to investigate the probability and the pattern of mediastinal lymph node metastases in patients with colorectal cancer with lung metastases. Presented at the 17th European Conference on General Thoracic Surgery, Krakow, Poland, May 31 June 3, 2009. *Corresponding author. Tel.: q49 941 369 2231; fax: q49 941 369 2206. E-mail address: szoketama@hotmail.com (T. Szöke). 2010 Published by European Association for Cardio-Thoracic Surgery 2. Patients and methods The criteria for resection of pulmonary metastases from colorectal carcinoma included technically resectable lung lesions, functional operability, no local recurrence of the primary lesion and no extrapulmonary metastases, with the exception of liver lesions, for which it is possible to completely remove the metastasis. A total of 24 metastasectomies were performed between 1 January and 31 December 2008 on patients at the Thoracic Surgery Centre Regensburg (Department of Thoracic Surgery, Krankenhaus Barmherzige Brüder and Division of Thoracic Surgery, University Regensburg, Germany) that were selected by the above-mentioned preconditions. The patients were evaluated by physical examination, computed tomography (CT) chest scans, bronchoscopy, and a lung function test. The primary site was monitored by endoscopy andyor CT-scan, and liver status was determined by ultrasonography or magnetic resonance imaging. The suspicion of mediastinal or hilar lymph node metastasis was not exclusion criteria, therefore, the PET-scanning was not used routinely during the preoperative examinations. 2.1. Procedure To facilitate mediastinal lymph node dissection and the removal of metastases localised in posterior segments, the

T. Szöke et al. / Interactive CardioVascular and Thoracic Surgery 10 (2010) 694 699 695 surgical approach was, in all cases, lateral thoracotomy. We did not use the video-assisted thoracic surgery (VATS) approach for metastasis surgery because palpation of the lung was not available. All patients with bilateral lesions received a sequential lateral thoracotomy, with an interval of three to four weeks. Peripheral metastases were localised in the external half of the lung and could be removed by wedge resection, while central metastases, which are adjacent to hilar or bronchus vessels, required lobectomy or laser resection to achieve R0-resection. When in doubt, the radicality was controlled by intraoperative histological examination. Mediastinal lymph node and hilar node dissection was carried out in all cases, independent of the preoperative radiological or the intraoperative findings. The mediastinal lymph node dissection always included, in the right-sided operation, the paratracheal, lower paratracheal, subcarinal, inferior mediastinal lymph nodes. The subaortic, subcarinal, inferior mediastinal compartments were removed in the left-sided thoracotomy. In cases of lobectomies or developed fissures, the lobar and interlobar lymph nodes were also removed. Of the 19 patients with colorectal cancer, 10 were women and nine were men, and the average age was 64.4 ("11.3) years. The colorectal cancer was in an advanced stage (stage III or IV) in most cases (68.3%), and 10 patients (52.6%) were previously treated for synchronous or metachronous (compared to the therapy used to treat primary tumour) liver metastases. The average disease-free interval (DFI) was 40.8 months and ranged from 12 to 98 months. All primary bowel resections were radical, and in two cases the histological examination revealed an R1 situation after the resection of synchronous liver metastases. These patients had no local recurrence in the liver at the time of the lung operation after adjuvant chemotherapy. Nine patients received adjuvant chemotherapy after the bowel resection. Two patients were treated with induction chemotherapy before lung metastasectomy and the metastases showed partial regression in both cases. Metachronous lung metastases developed in 18 patients after colorectal resection. One patient had synchronous lung metastases. In total, 24 operations were performed on these 19 patients (14 unilateral and five bilateral operations). Parenchyma-sparing resections were possible in 18 cases. Centrally localised metastases required four lobectomies, and two lobectomies combined with wedge resections. The clinical data of the primary tumours and the metastases are contained in Table 1. All patients were analysed retrospectively for sex, localisation and stage of primary tumour, presence or absence of synchronous or metachronous liver metastases, DFI, number and localisation of lung metastases, number and localisation of mediastinal lymph node metastases, and the diameter of the greatest metastasis. The date were analysed by SPSS for Windows software (SPSS Inc, Chicago, IL, USA). Categorical variables were 2 examined using the x -test, the continuous variables were analysed using a Mann Whitney test. Data are presented as median with range. Differences were considered significant when the P-0.05. Table 1 Patient characteristics ns19 Primary tumour Colon 11 Rectal 8 Stage I 4 IIA 2 IIIB 5 IIIC 2 IV 6 Grading 2 15 3 2 Unknown 2 Lymph nodes metastases N0 7 N1 6 N2 5 Unknown 1 Metastases Synchronous liver metastases 5 Synchronous lung metastases 1 Metachronous liver metastases 5 Metachronous lung metastases 18 Average DFI for lung metastases (months) 40.8 (12 98) Operation Wedge or laser resection 18 (75%) Lobectomy 4 (16.7%) Lobectomyqwedge resection 2 (8.3%) DFI, disease-free interval. 3. Results Intra- or postoperative complications (such as lesion of the thoracic duct, recurrent nerve palsy, lesion of the oesophagus or bronchi) as result of lymph node dissection were not detected. 3.1. Number and localisation of lung metastases A total of 56 lung metastases were removed. In 33.3% of the resections, a solitary nodule was found; two metastases were resected in 10 cases. The ratio of the affected lobes (upper vs. lower) was nearly equal, as was the ratio of the operated side. The mean diameter of the largest metastasis was 2.2 cm (ranging from 0.3 to 5.5 cm). Eight (33.3%) central metastases were removed lung with lobectomy or laser resection. Laser resection could be performed when the metastasis with central localisation did not involved the greater vessels or the bronchi of the lobe (Table 2). 3.2. Number and localisation of lymph node metastases The mean number of mediastinal lymph nodes removed was 11 (ranging from 6 to 28). The histological examination revealed that the tumour spread into mediastinal lymph nodes in eight operations (33.3% of all operations), and half of these (four cases) had only mediastinal involvement without hilar lymph node lesions. Multi-level lymph node involvement was found in only one operation (Table 2). Localisation of the central or the greatest peripheral metastasis on the right side occurred only in the lower lobe (four cases), while on the left side the lower and upper Work in Editorial New Ideas Progress Report Protocol Institutional Report ESCVS Article Proposal for Bailout Procedure Negative Results Follow-up Paper State-of-the-art Best Evidence Topic Nomenclature Historical Pages Brief Case Report Communication

696 T. Szöke et al. / Interactive CardioVascular and Thoracic Surgery 10 (2010) 694 699 Table 2 Pathological findings of resected pulmonary metastases (24 operations) Operations ns24 -sided 12 -sided 12 Number of metastases 56 1 8 2 10 3 3 4 2 11 1 Average 2.3 Upper lobe 26 Middle lobe 2 Upper lobe 28 Diameter of greatest metastasis (cm) 2.23 (0.3 5.5) Localisation Peripheral 16 Central 8 Lymph node metastases None 16 Hilar and mediastinal 4 Only mediastinal 4 Affected lymph node stations (according to Naruke) 3 (prevascular) 1 4 (lower paratracheal) 1 5 (subaortic) 3 7 (subcarinal) 3 8 (paraoesophageal) 1 The ratio of tumour infiltration in mediastinal lymph nodes was elevated in patients with two or more pulmonary metastases compared to patients with a solitary pulmonary metastasis (37.5% vs. 25%), although the difference was not statistically significant. The incidence of positive mediastinal lymph nodes was higher in the event of a more advanced pt- (pt2: 20% vs. pt4: 50%) and pn-stage (22.2%, 37.5% and 40%, respectively), without a significant difference. The presence of synchronous metastases at the time of the colorectal operation did not influence the probability of lymph node positivity significantly, although the risk was higher in initial stage IV than in the less advanced stages (57.1% vs. 23.5%, Ps0.112). The proportion of lymph node metastasis was highest in event of the synchronous liver metastases (57.1%), but the risk decreased when the liver metastasis developed only after the initial therapy for colorectal cancer (Table 4). A difference of 14% was seen between the diameter of the largest pulmonary metastasis with and without mediastinal lymph node metastases, but this was not statistically significant (Ps0.41). The DFI did not influence the development of lymph node metastases (Table 5). lobes were affected equally. On the left side, the subaortic lymph node station was most affected, and on the right side, metastasis was found in the subcarinal lymph nodes most often (Table 3). 3.3. Risk factors for lymph node metastases Neither gender nor side significantly correlated with the presence of mediastinal lymph node metastases. The probability of mediastinal involvement was three times higher if the primary tumour was rectum carcinoma than for colon cancer, although this difference was not significant. In the event of central localisation, the proportion of mediastinal lymph node metastasis was very high (62.5%), in contrast to peripheral metastases, and this difference proved to be significant (0.032). Table 3 Distribution of the lymph node metastases according to the localisation of the pulmonary lesion Localisation of the greatest or central metastasis ns8 Lower lobe Upper lobe Localisation of lymph node metastases* L8 L5, L7, L12 R4, R10 R7 R7, R12 R3 L5, L10, L12 L5 *Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 111:1718 1723. Table 4 The connection between the mediastinal lymph node metastases and the clinico-pathological features of the pulmonary metastases from colorectal cancer Mediastinal lymph node metastases n nq (No. of patients) (No. of patients) P-value Sex Male 8 (72.7%) 3 (27.3%) 0.562 Female 8 (61.5%) 5 (38.5%) Side 8 (66.7%) 4 (33.3%) 1 8 (66.7%) 4 (33.3%) Tumour localisation Peripheral 13 (81.3%) 3 (18.7%) 0.032 Central 3 (37.5%) 5 (62.5%) Number of metastases Soliter 6 (75%) 2 (25%) 0.54 Multiple 10 (62.5%) 6 (37.5%) Primary tumour Colon 12 (80%) 3 (20%) 0.074 Rectum 4 (44.4%) 5 (55.6%) pt a,b 2 4 (80%) 1 (20%) 0.725 3 10 (66.7%) 5 (33.3%) 4 1 (50%) 1 (50%) pn a,b 0 7 (77.8%) 2 (22.2%) 0.721 1 5 (62.5%) 3 (37.5%) 2 3 (60%) 2 (40%) M a 0 13 (76.5%) 4 (23.5%) 0.112 1 3 (42.9%) 4 (57.1%) Liver metastasis in history None 8 (72.8%) 3 (27.2%) 0.115 Synchron 2 (33.3%) 4 (66.7%) Metachron 6 (85.7%) 1 (14.3%) a b According to the primary tumour; the initial stage is unknown in 2 cases.

T. Szöke et al. / Interactive CardioVascular and Thoracic Surgery 10 (2010) 694 699 697 Table 5 Connection between the presenceyabsence of lymph node metastases and DFI and diameter of greatest metastasis, respectively (Mann Whitney test) Mediastinal lymph node metastasis n nq P-value DFI (months) 40.38 41.75 0.834 Diameter of greatest metastasis (cm) 2.14 2.44 0.417 DFI, disease-free interval. 4. Discussion Many published retrospective studies have shown encouraging results from resections of single or multiple colorectal pulmonary metastases, yielding five-year survival rates up to 60% w6x. It is well known that with non-small cell lung cancer, lymph node dissection improves correct staging and might improve survival w7x. The role of mediastinal lymph node metastasis in patients with lung metastases remains controversial, and the necessity of mediastinal lymph node dissection is still unclear. Generally, a systematic hilar and mediastinal lymph node dissection is not performed routinely in metastasis surgery w8x. An analysis of the International Registry of Lung Metastases revealed 5% of patients showed metastases to hilar or mediastinal lymph nodes, but only suspicious lymph nodes were removed. Welter et al. found 28 lymph node metastases in 266 operations, but systematic lymph node dissection was not performed in all cases w5x. In studies of systematically performed lymph node dissections, the proportion of lymph node metastases is significantly higher, and ranges between 22.2% and 31.3% w4, 9, 10x. In our series, pathological examination revealed mediastinal lymph node metastases in 33.3% of cases. It is now controversial whether lymph node involvement plays some role in prognosis. Many series analysing the prognostic factors do not include data about mediastinal lymph node involvement w6, 11x. Other publications did not show a prognostic role of lymph node positivity by multivariate analysis w12x, although survival was impaired by affected lymph nodes. Welter et al. and Ogata et al. found a prognostic impact of lymph node metastases, and compromised survival was revealed by multivariate analysis w5, 13x. In our patients, the period of the follow-up was too short to investigate the prognostic role of the mediastinal lymph node metastases. There are no data about the therapeutic effects of lymph node dissection. The removal of lymph node metastases can break the cascade of tumour progression, but the overall recurrence rate in patients with lung metastases and mediastinal lymph node metastases is 76.3%, in which the proportion of intrathoracic recurrence is only 23% w5x. We agree with Welter et al. that adjuvant chemotherapy should be discussed in this situation after complete metastasectomy and lymph node dissection w5x. We detected mediastinal lymph nodes involvement most often in the subcarinal nodes on the right side and in the subaortic nodes on the left side, but we could not detect an unambiguous pattern of lymphatic spread. Therefore, we believe that lymph node sampling cannot achieve the correct staging. Our results demonstrate that the proportion of noncontiguous mediastinal lymph node metastases is relatively high (50%). In Pfannschmidt et al. the ratio of skip node metastases was 20.3% in colorectal cancer w4x, which is comparable with non-small cell lung cancer. Riquet et al. suggested that direct lymphatic channels exist between the lung parenchyma and mediastinal lymph node stations w14x. The development of mediastinal lymph node involvement as a result of spread from the abdominal lymph nodes through the paravertebral venous plexus has been discussed for colorectal cancer w15x. Our results showing that central pulmonary lesions very often yields lymph node metastases, suggest that lymph node metastases arise from pulmonary metastases. Finally, we recommend mediastinal lymphadenectomy routinely during the resection of lung metastases from colorectal cancer. Because of the high proportion of mediastinal lymph node metastases (particularly with centrally localised metastases) and the ambiguous pattern of nodal involvement, only lymph node dissection can guarantee correct staging and the determination of an appropriate therapeutic concept. Longer follow-up is required to assess the prognostic role of mediastinal involvement. Further study is indicated to decide if preoperative PET-CTymediastinoscopy is helpful for selecting those patients most likely to benefit from surgical therapy of colorectal cancer metastases. References w1x Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18:581 592. w2x Brister SJ, de Varennes B, Gordon PH, Sheiner NM, Pym J. Contemporary operative management of pulmonary metastases of colorectal origin. Dis Colon Rectum 1988;31:786 792. w3x Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37 49. w4x Pfannschmidt J, Klode J, Muley T, Dienemann H, Hoffmann H. Nodal involvement of pulmonary metastasectomy: experiences in 245 patients. Ann Thorac Surg 2006;81:448 454. w5x Welter S, Jacobs J, Krbek T, Poettgen C, Stamatis G. Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer. Eur J Cardiothorac Surg 2007;31:167 172. w6x Watanabe I, Arai T, Ono M, Sugito M, Kawashima K, Ito M, Nagai K, Saito N. Prognostic factors in resection of pulmonary metastasis from colorectal cancer. Br J Surg 2003;90:1436 1440. w7x Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg 2000;70:358 365. w8x Internullo E, Cassivi SD, Van Raemdonck D, Friedel G, Treasure T, on behalf of the ESTS Pulmonary Metastasectomy Working Group. Pulmonary metastasectomy. A survey of current practice amongst members of the European Society of Thoracic Surgeons. J Thorac Oncol 2008; 3:1257 1266. w9x Inoue, M, Kotake Y, Nakagawa K, Fujiwara K, Fukuhara K, Yasumitsu T. Surgery for pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 2000;70:380 383. w10x Kanemitsu Y, Kato T, Hirai T, Yacui K. Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer. Br J Surg 2004;91:112 120. 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698 T. Szöke et al. / Interactive CardioVascular and Thoracic Surgery 10 (2010) 694 699 w11x Sakamoto T, Tsubota N, Iwanaga K, Yuki T, Matsuoka T, Yoshimura M. Pulmonary resection for metastases from colorectal cancer. Chest 2001;119:1069 1072. w12x Inoue M, Ohta M, Iuchi K, Matsumura A, Ideguchi K, Yasumitsu T, Nakagawa K, Fukuhara K, Maeda H, Takeda S, Minami M, Ohno Y, Matsuda H. Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 2004;78:238 244. w13x Ogata Y, Matono K, Hayashi A, Takamor S, Miwa K, Sasatomi T, Ishibashi N, Shida S, Shirouzu K. Repeat pulmonary resection for isolated recurrent lung metastases yields results comparable to those after first pulmonary resection in colorectal cancer. World J Surg 2005;29:363 368. w14x Riquet M, Hidden G, Debesse B. Direct lymphatic drainage of lung segment to the mediastinal nodes. An anatomic study on 260 adults. J Thorac Cardiovasc Surg 1989;97:623 632. w15x Kuba H, Sato N, Uchiyama A, Nakafusa Y, Mibu R, Yoshida K, Kuroiwa K, Tanaka M. Mediastinal lymph node metastasis of colon cancer: report of a case. Surg Today 1999;29:375 377. Conference discussion Dr. H. Hansen (Copenhagen, Denmark): It is an interesting paper on a hot topic, but I would like to hear about your preoperative evaluation of the patients. Had they PET scanning performed, had they a high-resolution CTscan performed, and, in conclusion, how many of your patients did you actually have suspicion of metastatic disease in the mediastinum before operation and in how many of your cases it was an unexpected finding? Dr. Szöke: PET investigation we performed not routinely in these cases. A routine chest CT examination revealed in two cases a suspicion of lymph node metastases from these eight patients or in these eight operations. Dr. K.S. Rammohan (Cardiff, UK): A question about the preoperative lymph node staging. You said that you had suspicious nodes in a couple of instances. Is a mediastinoscopy part of your workup? The Leeds group has shown that it is in colorectal metastases. If I remember correctly, they have done something to that effect. Do you use mediastinoscopy as part of your staging, and, if so, do you exclude these people if it is positive? Dr. Szöke: We perform mediastinoscopy not routinely, but about the survey of ESTS, 5% of thoracic surgeons in Europe perform routinely mediastinoscopy before a metastatic resection. Mr. J. Thorpe (Leeds, UK): Detlev Branscheid at the Istanbul meeting presented lymphadenectomy in metastasectomy and showed about 13% positive nodes. So, we went back to Leeds and said, well, why don t we do mediastinoscopy for these patients. So our paper also showed 13% this was in the pre-pet era had positive nodes. If you are looking at the incidence of positive PET scans, we do routinely PET scan for colorectal metastases now. But the incidence of warm or hot lesions for small colorectal metastases is very small. If you talk to the radiologists about this, PET scan is not very good for picking up internodal metastases or even hot lesions. I think it is a complicated area, and I am very pleased that you have raised it, because I think we should be doing lymph node assessment for these patients. It may explain why some patients have a poor prognosis and others do very well. Dr. Szöke: I think the problem is what is meant by mediastinal lymph node metastases in these patients. Literature data revealed that the prognosis in these patients is very, very low. That means if we reveal lymph node metastases mediastinally prior to operation, perhaps we have to exclude these patients from operation. Dr. S. Bolukbas (Wiesbaden, Germany): I do not understand the problem about involved mediastinal lymph nodes in the case of metastatic rectal or colorectal cancer, because these are distant metastases even if it is in the lung or it is in the mediastinum. In 1994, the Heidelberg group showed if you achieve complete resection, even in the mediastinum, you hardly find a survival difference. Dr. Szöke: A part of patients with rectal cancer received neoadjuvant chemoradiotherapy prior to colorectal operation. That can influence the lymph node metastases overall. Dr. G. Leschber (Berlin, Germany): May I make some comment. Do you think that the patients that you are looking at with a high rate of lymph node metastases are probably a very special population, because you mentioned in your paper that 70% also had liver metastases. We are doing a lot of metastasectomy as well, but I don t think that 70% of our patients have also either simultaneous, I think it was 58%, simultaneous liver metastases or metachronous. Do you think that is maybe one of the problems why you have such a high rate of lymph node involvement? Dr. Szöke: Our collective is a few patients. It is possible if the numbers are higher, then this proportion will change. Dr. R. Porta (Barcelona, Spain): Why didn t you remove station No. 9, for there any special reason? In your lymphadenectomy protocol you mentioned several lymph node stations but not No. 9, the pulmonary ligament station. Why didn t you remove it? Dr. Szöke: There is a mistake. We removed the lymph nodes from station 9. ecomment: Mediastinal lymph node dissection in pulmonary metastasectomy Authors: Christos Asteriou, Department of Thoracic Surgery, Theagenio Cancer Hospital, Thessaloniki, Greece; Nikolaos Barbetakis, Athanassios Kleontas, Chryssoula Doxani doi:10.1510/icvts.2009.213173a We have read with interest the article by Szöke et al. concerning the role of mediastinal lymphadenectomy during pulmonary metastasectomy w1x. The role of lymph node dissection in pulmonary metastasectomy from extrapulmonary malignancies as well as the role of preoperative mediastinoscopy are debatable issues. The basic policy is to do lymph node sampling during metastasectomy and not a systematic lymph node dissection, and this only for prognostic reasons. According to our institute s experience, mediastinal nodal involvement has definitely a negative impact on survival w2x. It is well established that lung metastases are predecessors of further systemic spread. So, it is mandatory to offer adjuvant chemotherapy in all cases, even though the resected metastasis is solitary, the resected lymph nodes are free of disease and preoperative biomarkers are within normal range. References w1x Szöke T, Kortner A, Neu R, Grosser C, Sziklavari Z, Wiebe K, Hofmann HS. Is the mediastinal lymphadenectomy during pulmonary metastasectomy of colorectal cancer necessary? Interact CardioVasc Thorac Surg 2010;10:694 699. w2x Barbetakis N, Asteriou C, Boukovinas I, Tsilikas C. The role of lymph node dissection in pulmonary resection for metastases from pulmonary cancer. Interact CardioVasc Thorac Surg 2009;9:644. ecomment: Mediastinal staging during pulmonary metastasectomy of colorectal cancer: why, when, and how? Authors: Serhan Tanju, Department of Thoracic Surgery, University Medical School, Capa, 34093 Istanbul, Turkey; Sukru Dilege doi:10.1510/icvts.2009.213173b Pre-peroperative mediastinal staging in patients with metastatic pulmonary disease, especially in candidates for metastasectomy, is still a matter of intense debate. Thus, I have read with interest the article by Szöke and colleagues who analysed the mediastinal lymphadenectomy during pulmonary metastasectomy for colorectal cancer w1x. Patients with colorectal cancer have an increased risk of developing second primary cancer. According to Noura et al. w2x, the frequency of postoperative extracolorectal cancer was 12.6%. In this group of patients, the frequency of primary lung and gastric cancer was significantly higher than the other malignancies w2x. We know that in some patients with a medical history of colorectal cancer, thoracotomy can be performed according to positron emission tomography/computed tomography (PET/ CT) findings without definitive diagnosis of a pulmonary nodule. During thoracotomy, frozen section analysis does not always confirm that the lesion is primary lung cancer or a metastatic lesion, so hilar and mediastinal lymph node sampling has to be performed to achieve correct mediastinal stage for primary lung cancer and also to decide appropriate postoperative oncological treatment for both probability of malignancies. The other question is: which method of intraoperative mediastinal staging has to be performed? Mediastinal and hilar lymph node sampling w3x can be

T. Szöke et al. / Interactive CardioVascular and Thoracic Surgery 10 (2010) 694 699 699 the choice of mediastinal staging in patients if they have negative mediastinal uptake on FDG-PET/CT or if intraoperative frozen section analysis does not confirm lymph node metastasis. On the other hand, lymph node dissection w3x can be performed in case of metastatic mediastinal lymph node which is proved via frozen section during pulmonary metastasectomy. References w1x Szöke T, Kortner A, Neu R, Grosser C, Sziklavari Z, Wiebe K, Hofmann HS. Is the mediastinal lymphadenectomy during pulmonary metastasectomy of colorectal cancer necessary? Interact CardioVasc Thorac Surg 2010;10:694 699. w2x Noura S, Ohue M, Seki Y, Tanaka K, Motoori M, Kishi K, Miyashiro I, Ohigashi H, Yano M, Ishikawa O, Tsukuma H, Murata K, Kameyama M. Second primary cancer in patients with colorectal cancer after a curative resection. Dig Surg 2009;26:400 405. w3x Zhong W, Yang X, Bai J, Yang J, Manegold C, Wu Y. Complete mediastinal lymphadenectomy: the core component of the multidisciplinary therapy in resectable non-small cell lung cancer. Eur J Cardiothorac Surg 2008; 34:187 195. Work in Editorial New Ideas Progress Report Protocol Institutional Report ESCVS Article Proposal for Bailout Procedure Negative Results Follow-up Paper State-of-the-art Best Evidence Topic Nomenclature Historical Pages Brief Case Report Communication