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Re: Reflections and proposals for the standardization of lymphadenectomy for gastric cancer
European Journal of Surgical Oncology 2000; 26: 522–523 Available online at http://www.idealibrary.com on
CORRESPONDENCE doi:10.1053/ejso.2000.0937
Sir, Re: Reflections and proposals for the standardization of lymphadenectomy for gastric cancer I am writing with reference to the excellent paper by Dr Elias ‘Reflections and proposals for the standardization of lymphadenectomy for gastric cancer’ published in the section ‘For Debate’.1 I agree with most of the points raised by the Author, and especially with the need to abandon the time-honoured but now old-fashioned classification of lymph nodes by the Japanese Research Society for Gastric Cancer. There are, however, three points worthy of consideration which have led me to conclusions somewhat different from those of Dr Elias. 1. It is true that the UICC 1997 Classification,2 following a thorough examination of the study by the German Gastric Cancer Study Group and the Erlangen group,3 has recommended the examination of at least 15 lymph nodes after lymphadenectomy for gastric carcinoma, but this does not necessarily imply that the finding of 15 negative lymph nodes allows an accurate assessment of the stage as N0. In our experience of over 600 patients enrolled in a prospective randomized protocol comparing subtotal vs total gastrectomy,4 we discovered that the chance of finding a positive lymph node was highly dependent on the number of retrieved lymph nodes (Fig. 1). This proved to be true till a plateau of 20–25 lymph nodes was reached: after that number the percentage of positive lymph nodes remained constant. These data are perfectly in line with the common occurrence of the well-known ‘Will Rogers effect’ when comparing the outcome of some selected stages of
patients undergoing limited or extended lymphadenectomy. 2. According to our multicentre experience,5 when we compared the outcome of patients undergoing a R0 gastrectomy by the scope of lymphadenectomy, we found that, after adjustment for other prognostic effects, patients who received a volume of resection including at least 20–25 lymph nodes had the best chances of survival (Fig. 2). Furthermore, it is worthy of note that in our multicentre trial5 we had—with a median of 19–23 lymph nodes in the specimen of subtotal and total gastrectomy, respectively—a 5-year survival quite similar to that reported by some Japanese authors.6 3. Finally, as a surgeon and oncologist, I do not advocate the launch of a new trial comparing ‘the two simplified and reproducible D1 and D2 lymphadenectomies without spleno-pancreatectomy’. In fact, since in many European Institutions morbidity and mortality after a D2 gastrectomy are reasonably low and acceptable,7 such a trial would probably lead to the meaningless conclusion that after both D1 and D2 post-operative mortality is similar—and with the same being true for the oncological outcome, though this may be a little worse after D1. Since we know that post-operative mortality is not affected by the scope of the lymphadenectomy—being 1.82%, 1.80% and 1.75% for Ζ15, 16–25 and >25 retrieved lymph nodes, respectively—within the specimen in our study (unpublished data), and since some Western series8–14 reported a clinical benefit for the extended resection when comparing R0 D1 to R0 D2, we do not think that this trial would represent a qualitative step forward in the treatment of gastric cancer. 3
1.0 logHR of death
2
Prob(N+)
0.8 0.6
High risk category
1
0
0.4 Low risk category
–1
0.2
0
0.0 0
20 40 60 80 Number of resected lymph nodes
100
Fig. 1. Probability of finding a metastatic lymph node by the number of retrieved nodes (unpublished data). 0748–7983/00/050522+02 $35.00/0
100 20 40 60 80 Number of resected lymph nodes
Fig. 2. Probability of death as a function of the number of the resected lymph nodes in two extreme categories of patients, defined at high or low risk depending on the prognostic factors (unpublished data). 2000 Harcourt Publishers Ltd
523
Correspondence I think we should not embark upon a demanding prospective trial just to demonstrate that two approaches are similar, or that one is worse than the other, but only if we expect that one gives a consistent benefit. In conclusion, our therapeutic options are, from a practical point of view, quite similar to those proposed by Dr Elias. We suggest a lymphadenectomy, basically a modified D2 similar to that described by Elias,1 which should contain 25 lymph nodes or more and which is more focused on the number rather than on the site of lymph nodes. We define such lymphadenectomy as a ‘>D1’ or ‘over D1’ lymphadenectomy and this represents our current standard in the treatment of advanced cancer of the stomach. Federico Bozzetti MD, Surgeon, Oncologist, Residenza Le Querce, Milano Due, 20030 Segrate (MI), Italy
References 1. Elias D. Reflections and proposals for the standardization of lymphadenectomy for gastric carcinoma. Eur J Surg Oncol 2000; 26: 6–10. 2. Sobin LH, Wittekind CH (eds). TNM classification. TNM Classification of Malignant Tumours. International Union against Cancer 5th edn. New York: John Wiley and Sons, 1997: 59. 3. Roder JD, Bottcher K, Busch R, et al. Classification of regional lymph node metastasis from gastric carcinoma. Cancer 1998; 82: 621–31. 4. Bozzetti F, Marubini E, Miceli R, Bonfanti G, Piano C, Crose N, Gennari L, The Italian Gastrointestinal Tumour Study Group. Total vs subtotal gastrectomy. Surgical morbidity and mortality rates in a multicenter Italian randomized trial. Ann Surg 1997; 226: 613–20. 5. Bozzetti F, Marubini E, Bonfanti G, Miceli R. Subtotal versus total gastrectomy for gastric cancer: five-year survival in a multicenter randomized Italian trial. Ann Surg 1999; 230: 170–8. 6. Maruyama K, Okabayashi K, Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg 1987; 11: 418–26. 7. Degiuli M, Sasako M, Ponti A, Soldati T, Danese F, Calvo F. Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian Gastric Cancer Study Group. Prospective multicenter surgical study. Clin Oncol 1998; 16: 1490–3. 8. Pacelli F, Doglietto GB, Bellantone R, Alfieri S, Sgadari A, Crucitti F. Extensive versus limited lymph node dissection for gastric cancer: a comparative study of 320 patients. Br J Surg 1993; 80: 1153–6. 9. Gall FP, Hermanek P. New aspects in the surgical treatment of gastric carcinoma—a comparative study of 1636 patients operated on between 1969 and 1982. Eur J Surg Oncol 1985; 11: 219. 10. Siewert JR, Bo¨ttcher K, Roder JD, et al. Prognostic relevance of systematic lymph node dissection in gastric carcinoma. Br J Surg 1993; 80: 1015–8. 11. Viste A, Svanes K, Janssen CW Jr, et al. Prognostic importance of radical lymphadenectomy in curative resections for gastric cancer. Eur J Surg 1994; 160: 497–502. 12. Fass J, Schumpelick V. Principles of radical surgery in gastric carcinoma. Hepatogastroenterology 1989; 36: 13. 13. Volpe CM, Koo J, Miloro SM, et al. The effect of extended
lymphadenectomy on survival in patients with gastric adenocarcinoma. J Am Coll Surg 1995; 181: 56–64. 14. De Manzoni G, Verlato G, Guglielmi A, et al. Prognostic significance of lymph node dissection in gastric cancer. Br J Surg 1996; 83: 1604–7.
doi:10.1053/ejso.2000.0938
Sir, Reply to Professor Bozzetti I thank Professor Bozzetti for commenting on my reflections and proposals. I should like to make two points: (1) I clearly stated in my papers1,2 that a modified D2 lymphadenectomy is recommended and that such a lymphadenectomy should contain 25 lymph nodes or more. However, many groups perform a D1 lymphadenectomy following the negative results of the Dutch randomized trial. Such a D1 lymphadenectomy should contain at least 15 lymph nodes, which is a recommendation of the UICC TNM classification of 1997.3 The corollary is that, at least 15 lymph nodes must be studied, to allow a patient to be staged as N0. Sadly, it is common to see pathological reports with less than 15 lymph nodes examined, or pathologists only examining until at least one lymph node is discovered as involved. (2) In theory, only a new randomized prospective trial could prove our hypothesis. However, practically speaking, I agree completely with the opinion of Professor Bozzetti that we have already indirect proof that the modified D2 lymphadenectomy, without spleno-pancreatectomy, is now the gold standard for many groups, and that this new randomized study is not necessary. Finally, I am very happy and honoured that Professor Bozzetti joins me in recommending this modified D2 lymphadenectomy as standard treatment in advanced gastric cancer, and I thank him for his assistance. Dominique Elias Department of Surgical Oncology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805, Villejuif Cedex, France
References 1. Elias D. Reflections and proposals for the standardization of lymphadenectomy for gastric carcinoma. Eur J Surg Oncol 2000; 26: 6–10. 2. Elias D. Reflections and proposals for the worldwide standardization of lymphadenectomy for gastric carcinoma. J Surg Oncol 1999; 71: 120–2. 3. Sobin LH, Wittekind C. UICC. TNM classification of malignant tumor. (5th Edn). New York: Wyley-Liss Pub., 1997: 63. 2000 Harcourt Publishers Ltd
CORRESPONDENCE doi:10.1053/ejso.2000.0937
Sir, Re: Reflections and proposals for the standardization of lymphadenectomy for gastric cancer I am writing with reference to the excellent paper by Dr Elias ‘Reflections and proposals for the standardization of lymphadenectomy for gastric cancer’ published in the section ‘For Debate’.1 I agree with most of the points raised by the Author, and especially with the need to abandon the time-honoured but now old-fashioned classification of lymph nodes by the Japanese Research Society for Gastric Cancer. There are, however, three points worthy of consideration which have led me to conclusions somewhat different from those of Dr Elias. 1. It is true that the UICC 1997 Classification,2 following a thorough examination of the study by the German Gastric Cancer Study Group and the Erlangen group,3 has recommended the examination of at least 15 lymph nodes after lymphadenectomy for gastric carcinoma, but this does not necessarily imply that the finding of 15 negative lymph nodes allows an accurate assessment of the stage as N0. In our experience of over 600 patients enrolled in a prospective randomized protocol comparing subtotal vs total gastrectomy,4 we discovered that the chance of finding a positive lymph node was highly dependent on the number of retrieved lymph nodes (Fig. 1). This proved to be true till a plateau of 20–25 lymph nodes was reached: after that number the percentage of positive lymph nodes remained constant. These data are perfectly in line with the common occurrence of the well-known ‘Will Rogers effect’ when comparing the outcome of some selected stages of
patients undergoing limited or extended lymphadenectomy. 2. According to our multicentre experience,5 when we compared the outcome of patients undergoing a R0 gastrectomy by the scope of lymphadenectomy, we found that, after adjustment for other prognostic effects, patients who received a volume of resection including at least 20–25 lymph nodes had the best chances of survival (Fig. 2). Furthermore, it is worthy of note that in our multicentre trial5 we had—with a median of 19–23 lymph nodes in the specimen of subtotal and total gastrectomy, respectively—a 5-year survival quite similar to that reported by some Japanese authors.6 3. Finally, as a surgeon and oncologist, I do not advocate the launch of a new trial comparing ‘the two simplified and reproducible D1 and D2 lymphadenectomies without spleno-pancreatectomy’. In fact, since in many European Institutions morbidity and mortality after a D2 gastrectomy are reasonably low and acceptable,7 such a trial would probably lead to the meaningless conclusion that after both D1 and D2 post-operative mortality is similar—and with the same being true for the oncological outcome, though this may be a little worse after D1. Since we know that post-operative mortality is not affected by the scope of the lymphadenectomy—being 1.82%, 1.80% and 1.75% for Ζ15, 16–25 and >25 retrieved lymph nodes, respectively—within the specimen in our study (unpublished data), and since some Western series8–14 reported a clinical benefit for the extended resection when comparing R0 D1 to R0 D2, we do not think that this trial would represent a qualitative step forward in the treatment of gastric cancer. 3
1.0 logHR of death
2
Prob(N+)
0.8 0.6
High risk category
1
0
0.4 Low risk category
–1
0.2
0
0.0 0
20 40 60 80 Number of resected lymph nodes
100
Fig. 1. Probability of finding a metastatic lymph node by the number of retrieved nodes (unpublished data). 0748–7983/00/050522+02 $35.00/0
100 20 40 60 80 Number of resected lymph nodes
Fig. 2. Probability of death as a function of the number of the resected lymph nodes in two extreme categories of patients, defined at high or low risk depending on the prognostic factors (unpublished data). 2000 Harcourt Publishers Ltd
523
Correspondence I think we should not embark upon a demanding prospective trial just to demonstrate that two approaches are similar, or that one is worse than the other, but only if we expect that one gives a consistent benefit. In conclusion, our therapeutic options are, from a practical point of view, quite similar to those proposed by Dr Elias. We suggest a lymphadenectomy, basically a modified D2 similar to that described by Elias,1 which should contain 25 lymph nodes or more and which is more focused on the number rather than on the site of lymph nodes. We define such lymphadenectomy as a ‘>D1’ or ‘over D1’ lymphadenectomy and this represents our current standard in the treatment of advanced cancer of the stomach. Federico Bozzetti MD, Surgeon, Oncologist, Residenza Le Querce, Milano Due, 20030 Segrate (MI), Italy
References 1. Elias D. Reflections and proposals for the standardization of lymphadenectomy for gastric carcinoma. Eur J Surg Oncol 2000; 26: 6–10. 2. Sobin LH, Wittekind CH (eds). TNM classification. TNM Classification of Malignant Tumours. International Union against Cancer 5th edn. New York: John Wiley and Sons, 1997: 59. 3. Roder JD, Bottcher K, Busch R, et al. Classification of regional lymph node metastasis from gastric carcinoma. Cancer 1998; 82: 621–31. 4. Bozzetti F, Marubini E, Miceli R, Bonfanti G, Piano C, Crose N, Gennari L, The Italian Gastrointestinal Tumour Study Group. Total vs subtotal gastrectomy. Surgical morbidity and mortality rates in a multicenter Italian randomized trial. Ann Surg 1997; 226: 613–20. 5. Bozzetti F, Marubini E, Bonfanti G, Miceli R. Subtotal versus total gastrectomy for gastric cancer: five-year survival in a multicenter randomized Italian trial. Ann Surg 1999; 230: 170–8. 6. Maruyama K, Okabayashi K, Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg 1987; 11: 418–26. 7. Degiuli M, Sasako M, Ponti A, Soldati T, Danese F, Calvo F. Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian Gastric Cancer Study Group. Prospective multicenter surgical study. Clin Oncol 1998; 16: 1490–3. 8. Pacelli F, Doglietto GB, Bellantone R, Alfieri S, Sgadari A, Crucitti F. Extensive versus limited lymph node dissection for gastric cancer: a comparative study of 320 patients. Br J Surg 1993; 80: 1153–6. 9. Gall FP, Hermanek P. New aspects in the surgical treatment of gastric carcinoma—a comparative study of 1636 patients operated on between 1969 and 1982. Eur J Surg Oncol 1985; 11: 219. 10. Siewert JR, Bo¨ttcher K, Roder JD, et al. Prognostic relevance of systematic lymph node dissection in gastric carcinoma. Br J Surg 1993; 80: 1015–8. 11. Viste A, Svanes K, Janssen CW Jr, et al. Prognostic importance of radical lymphadenectomy in curative resections for gastric cancer. Eur J Surg 1994; 160: 497–502. 12. Fass J, Schumpelick V. Principles of radical surgery in gastric carcinoma. Hepatogastroenterology 1989; 36: 13. 13. Volpe CM, Koo J, Miloro SM, et al. The effect of extended
lymphadenectomy on survival in patients with gastric adenocarcinoma. J Am Coll Surg 1995; 181: 56–64. 14. De Manzoni G, Verlato G, Guglielmi A, et al. Prognostic significance of lymph node dissection in gastric cancer. Br J Surg 1996; 83: 1604–7.
doi:10.1053/ejso.2000.0938
Sir, Reply to Professor Bozzetti I thank Professor Bozzetti for commenting on my reflections and proposals. I should like to make two points: (1) I clearly stated in my papers1,2 that a modified D2 lymphadenectomy is recommended and that such a lymphadenectomy should contain 25 lymph nodes or more. However, many groups perform a D1 lymphadenectomy following the negative results of the Dutch randomized trial. Such a D1 lymphadenectomy should contain at least 15 lymph nodes, which is a recommendation of the UICC TNM classification of 1997.3 The corollary is that, at least 15 lymph nodes must be studied, to allow a patient to be staged as N0. Sadly, it is common to see pathological reports with less than 15 lymph nodes examined, or pathologists only examining until at least one lymph node is discovered as involved. (2) In theory, only a new randomized prospective trial could prove our hypothesis. However, practically speaking, I agree completely with the opinion of Professor Bozzetti that we have already indirect proof that the modified D2 lymphadenectomy, without spleno-pancreatectomy, is now the gold standard for many groups, and that this new randomized study is not necessary. Finally, I am very happy and honoured that Professor Bozzetti joins me in recommending this modified D2 lymphadenectomy as standard treatment in advanced gastric cancer, and I thank him for his assistance. Dominique Elias Department of Surgical Oncology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805, Villejuif Cedex, France
References 1. Elias D. Reflections and proposals for the standardization of lymphadenectomy for gastric carcinoma. Eur J Surg Oncol 2000; 26: 6–10. 2. Elias D. Reflections and proposals for the worldwide standardization of lymphadenectomy for gastric carcinoma. J Surg Oncol 1999; 71: 120–2. 3. Sobin LH, Wittekind C. UICC. TNM classification of malignant tumor. (5th Edn). New York: Wyley-Liss Pub., 1997: 63. 2000 Harcourt Publishers Ltd