Justification for endoscopic treatment of subgroups of early gastric cancer

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9. Parikh D. Johnson M. Chagla L, Lowe D, McCulloch E D2 gastrectomy: lessons from a prospective audit of the learning curve. Br J Surg 1996; 83:1595-9. 10. Siewert JR, Bottcher K, Roder JD, Busch R, Hermanek E Meyer HJ. Prognostic relevance of systematic lymph node dissection in gastric carcinoma. German Gastric Carcinoma Study Group [see comments]. Br J Surg 1993; 80: 1015-8. I I. Volpe CM, Koo J, Miloro SM, Driscoll DL, Nava HR, Douglass HO, Jr. The effect of extended lymphadenectomy on survival in patients with gastric adenocarconoma. J Am Coil Surg 1995; 181: 56-64. 12. 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 [see comments]. Br J Surg 1993; 80: 1153-6. 13. Bonenkamp JJ, Songun 1, Hermans J, et al. Randomised comparison ofmorbidity after DI and D2 dissection for gastric cancer in 996 Dutch patients [see comments]. Lancet 1995; 345: 745-8. 14. Sue-Ling HM, Martin I, Griffith J, et aL Early gastric cancer: 46 cases treated in one surgical department. Gut 1992; 33: 1318-22. 15. Griffith JP, Sue-Ling HM, Martin 1, et al. Preservation of the spleen improves survival after radical surgery for gastric cancer. Gut 1995; 36: 684-90. 16. Wanebo HJ, Kennedy BJ, Winchester DE Stewart AK, Fremgen AM. Role of splenectomy in gastric cancer surgery: adverse effect of elective splenectomy on longterm survival. J Am Coil Surg 1997; 185: 177-84. 17. Otsuji E, Yamaguchi T, Sawai K, Ohara M, Takahashi T. End results of simultaneous splenectomy in patients undergoing total gastrectomy for gastric carcinoma. Surgery 1996; 120: 40-4.

18. Maehara Y, Moriguchi S, Yoshida M, Takahashi I, Korenaga D, Sugimachi K. Splenectomy does not correlate with length of survival in patients undergoing curative total gastrectomy for gastric carcinoma. Univariate and multivariate analyses. Cancer. 1991; 67: 3006-9. 19. Hisamichi S. Screening for gastric cancer. World J Surg 1989; 13:31-7. 20. Jatzko GR, Lisborg PH, Denk H, Klimpfinger M, Stettner HM. A 10-year experience with Japanese-type radical lymph node dissection for gastric cancer outside of Japan. Cancer 1995; 76: 1302-12. 21. McCulloch E Should general surgeons treat gastric carcinoma? An audit of practice and results, 1980-1985. Br J Surg 1994; 81: 417-20. 22. Wu CW, Hsieh MC, Lo SS, et al. Morbidity and mortality after radical gastrectomy for patients with carcinoma of the stomach. J Am Coil Surg 1995; 181: 26-32. 23. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after Dl and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. (In prep.) 24. Siewert JR, Kestlmeier R, Busch R, et al. Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN 1 lymph node metastases. Br J Surg 1996; 83: 1144-7. 25. lshida K, Katsuyama T, Sugiyama A, Kawasaki S. Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer 1997; 79: 1069-76. 26. Hayes N, Karat D, Scott D J, Raimes SA, Griffin SM. Radical lymphadenectomy in the management of early gastric cancer. Br J Surg 1996; 83: 1421-3. 27. de Dombal FT, Price AB, Thompson H, et al. The British Society of Gastroenterology early gastric cancer/dysplasia survey: an interim report [see comments]. Gut 1990; 31: 115-20.

Justification for endoscopic treatment of subgroups of early gastric cancer Gerhard R. Jatzko and Peter H. Lisborg S u r g i c a l D e p a r t m e n t , H o s p i t a l o f B a r m h e r z i g e Briidel; A u s t r i a

Introduction Early gastric cancer (EGC) is defined as gastric carcinoma limited to the mucosa and submucosa of the gastric wall, corresponding to U I C C category pT1-a or pT 1-b. i The term E G C was introduced in 1962 by the Japanese Gastroenterological Endoscopic Society for this early tumour entity, regardless of the presence or absence of

Correspondence to: Prim. Univ. Prof. Dr. Gerhard Jatzko, Surgical Department, Hospital of Barmherzige Brtider Teaching Hospital of the Faculty of Medicine, University of Vienna, Spitalgasse 26, A-9300 St. Veit/Glan, Austria. Fax: +43 4212 499 400.

lymph-node metastases. 2'3 The overall prognosis achievable with radical surgical therapy was favourable and 5-year survival rates up to 95% have been reported repeatedly by Japanese institutions and also by some specialized centres in Europe and the USA. 4-8 As the prognosis of E G C is not only dependent on the depth of tumour infiltration, but also on lymph-node status, great differences have been reported in patient outcome related to the number and groups of lymph nodes involved. Intensive screening programmes, and perhaps somewhat different histopathological criteria o f this early cancer, 4s have led to E G C rates of 40% and above in Japan. s'j°-t2 Japanese institutions nowadays are able to provide a nearly exact prediction of lymph-node metastasis of E G C present at the

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time of operation) °'t3:4 This prediction is largely dependent on the presence of a mucosal or submucosal carcinoma, the macroscopic type of EGC, tumour size and also on biological features such as differentiation, tumour typing and growth patterns) 3 ~6

Japan was superior to D1 lymphadenectomy related to 5year survival and this benefit was also present for lymphnode-negative EGC. Similar results, inexplicable at first glance, have been found by Maehara, t2 Siewert, 8 Harrison 7 and others. A possible explanation is the presence of micrometastases in the removed nodes, only detectable by sensitive immunohistochemical staining methods. 2~

Lymph-node involvement and pathology Lymph-node metastases for EGC were found in about 9% of patients in Japanese series. For mucosal carcinomas, the frequency of positive nodes ranges between 0 and 17%; for submucosal carcinomas this is between 13 and 30%. The corresponding values in Europe are 1.5-7% and 4-12.3%, respectively) 5 In our own recent series, mucosal invasion showed positive nodes in 1.7% and submucosal invasion occurred in 22.7%) 7 The percentage of positive nodes in Japanese reports corresponds to the tumour size, the macroscopic appearance of the EGC, tumour grading and the type of invasion. Tumours of less than I cm in diameter have shown positive nodes in 4% of cases, while tumours of over 4-cm diameter had positive nodes in 18%°. In mucosal cancer, lymph-node metastases were always limited to the perigastric nodes, whereas submucosal cancers have also shown lymph-node metastases to groups 2 and 3. Ulceration and depressed lesions (type Ilc) were associated with positive nodes in 2-3%0 of cases of mucosal EGC, whereas nonulcerated types did not show lymph-node metastases. Conversely, positive lymph nodes were found in 23.3% of ulcerated submucosal tumours. ~5:6:8 These clinical and histopathological findings related to node-negative EGC have led to the establishment of minimally invasive treatment for cure in subgroups of E G C ) ~ ~6.~8.~9 Curative minimally invasive treatment for mucosal carcinomas is justified in EGC when protruded lesions (type 1) or elevated (type Ila) and flat lesions (type lib) are well or moderately differentiated and smaller than 25 mm in diameter. For depressed types (llc), tumours should not be more than 15mm in diameter and should be well differentiated. For these lesions the absence of lymph-node metastasis is judged on the basis of data accumulated from histopathological examination of surgical specimens) 3 ~6.~.~9 Ulcerated lesions (type III) have failed to be an indication for local therapy as recurrence resulted in 18.9%) 5 Methods employed for minimally invasive treatment, provided that endoscopic ultrasound imaging shows the lesions limited to the mucosa, are endoscopic mucosectomy, endoscopic coagulation, laser therapy, cryosurgery, microwave coagulation and combined endoscopic laparoscopic local excisions. The technical approach for endoscopic mucosal resection has been recently described in detail by Takeshita et a l . 19 It is very surprising that this development was started in Japan, where radical D2lymphadenectomy for EGC could achieve excellent cure rates with minimal complications and post-operative mortality:.5:0 ~2 In the Tokyo National Cancer Center Hospital series (from 1981 to 1991) of 5416 resected gastric cancers, 5-year survivals were 94% for stage la, 90% for stage lb and 76% for stage II, with a post-operative mortality of only 0.4% for the entire series. 2° Radical D2 lymphadenectomy in

Surgical classification As we have emphasized recently, ~7the classification of gastric cancer should perhaps be reconsidered from the surgical point of view. EGC is a term which takes into consideration only the depth of infiltration, regardless of lymph-node involvement. EGC will vary considerably in terms' of prognosis depending on type (i.e. mucosal or submucosal) and especially on lymph-node status. On the other hand, pT2a tumours have an excellent prognosis with radical surgery alone, similar to submucosal tumours. It would be advisable, therefore, to differentiate between localized EGC with possibilities for minimal invasive treatment as successfully performed in the Japanese series, early gastric cancers (including tumours limited to the propria muscularis layer) treated successfully with radical surgery alone, and advanced gastric cancers requiring some adjuvant therapy regimens. In Japan, minimally invasive treatment for EGC (mucosal type) is offered for a subgroup of gastric cancer patients ~3 ~6. ~s,t~ with only a very low or unlikely probability of lymphnode metastasis to prevent unnecessary radical surgery with possible post-operative morbidity. Survival for these patients is similar to that for patients treated by radical surgery, but quality of life is undisturbed. Similar considerations have led to the establishment of local excision for low-risk pTl rectal carcinomas. For non-invasive low-grade pTl rectal tumours, the probability of lymph node metastasis was found to be less than the post-operative mortality following radical surgery.-'-"

Conclusions In Western countries, where D2 lymphadenectomy generally has a high morbidity and mortality, endoscopic mucosal resection or other forms of minimally invasive techniques should be adopted. Neither the previous Dutch or UK Medical Research Council trials-'3'u could establish any advantage for D2 over DI lymphadenectomy. In addition, radical lymph-node dissection was associated with a very high mortality and morbidity, so that the radical Japanesetype lymph-node dissection for these subtypes of mucosal EGC would have to be viewed as a very dangerous and unnecessary surgical procedure in most Western countries. As results for minimally invasive treatment in Japan are superior or equal to results achieved for mucosal EGC in Western countries with D1 lymphadenectomy only, endoscopic mucosectomy or combined endoscopic laparoscopic procedures should also be adopted in Europe. This endoscopic process enables an exact histological examination of the fully resected mucosal lesion with

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assessment. Radical surgery should be offered for patients at high risk for lymph-node metastasis due to a subsequently diagnosed submucosal invasion or to inadequate resection margins. Post-operative morbidity and mortality due to comorbidity in patients suffering from gastric cancer in Europe justifies minimally invasive techniques for mucosal E G C in clinical trials. For high-risk and older patients with comorbidity, minimally invasive procedures offer not only a maintained quality of life but also a considerable decrease in morbidity and mortality. In the high-risk mucosal E G C and in submucosal E G C (with high probability for lymph-node metastasis), radical D2, D3 lymphadenectomy should be the surgical approach of choice. Survival rates similar to Japanese reports can be achieved in specialized Western centres 25 without affecting morbidity and mortality.

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