The ideal lymphadenectomy for gastric cancer (GC) should accurately stage the extent of disease and predict prognosis; in addition it should have the potential to improve survival by selectively and completely removing all metastatic lymph nodes (LN), with minimal morbidity and mortality.
Unfortunately the optimal extent of lymph node dissection (LND) for GC has not been determined and is certainly not standardized.
At the time of resection, the macroscopic assessment of nodal metatstases is notoriously unreliable, and the intraoperative assessment of microscopic LN metastases is costly and impractical. Furthermore the pattern of lymph node involvement depends on numerous factors, including location of the primary tumor and depth of tumor invasion.
Although the incidence of GC has decreased significantly in the United States over the past several decades, a large percentage of patients still present with advanced disease. The need for an effective adjuvant therapy is clear, but an R0 surgical resection remains the cornerstone of effective curative therapy ( 1 ). In case of locoregional disease complete macroscopic and microscopic resection ( R0 ) of the tumor ( T ) is a strong indipendent prognostic factor. Patients with locally advanced carcinoma (T 3-4) have a 20-31% chance for five year survival after complete (R0) resection compared to 0% after R1 or R2 resections
( 2 ).
Resection of two or more adjacent organs in advanced gastric adenocarcinoma is associated with a greater risk of developing a complication. The use of a graded surgical complication scale is needed for better reporting and comparison of complications. Achieving an R0 resection should still be considered the goal, even in locally advanced gastric cancer, but resection of additional organs should be performed judiciously
( 4, 5,
34,
35,
36 ).
The routine use of laparoscopy to rule out the presence of radiographically unidentified metastases should be the first step in attempting an R0 resection. In general patients with M1 disease are referred for systemic chemotherapy and selective use of resection. HJ Kim and colleagues advocate a pragmatic approach, limiting the role of operation when dictated by the biology of the disease and reserving aggressive surgical resection for patients with high curative potential.
In general at MSKCC patients with ultrasound T1 EGCs (with one or more unfavorable clinicopathologic features) are surgically resected with a limited lymphadenectomy. Although nearly 20% of EGC have positive nodes, the majority of these nodes are located in the perigastric LN stations. EGCs with favorable features (small size, no submucosal invasion, well differentiated ) can be considered for EMR, or a limited open versus laparoscopic gastric resection
( 1 ).
Takaki Yoshikawa et al underline that the most widely applied treatment or early gastric cancer in Japan and in some European countries has been total or subtotal gastrectomy with D2 lymphadenectomy. But D2 lymphadenectomy in patients with early GC had little survival benefit because (1) metastasis to level 2 nodes was rare, (2) most causes of death were not related to the tumor, and (3) more than half the recurrences were hematogenous.Therefore use of radical lymphadenectomy for early GC should be limited
( 3 ).
In contrast, T2 M0 and T3 M0 GCs should include an omentectomy, removal of perigastric nodes and nodes along the left gastric artery. HJ Kim and colleagues favor the extended (D2) lymphadenectomy because of the superior staging information. Labeling of N2 nodes helps to ensure that the pathologist examines these high-risk areas. Distal pancreatic and splenic resection should be avoided and performed only for direct organ involvement. In addition to the ELND and radical gastric resection, the authors perform an omental bursectomy for T3 tumors in an effort to improve local control. Lymphatics along the splenic artery lie in the wall of the bursa fusing with the parietal peritoneum and transverse mesocolon to form the fascia of Told.The authors do not routinely perform a D3 ELND in patients resected with curative intent, because the staging information is not significantly improved, and the morbidity rate may be higher.
The increasing frequency of the more aggressive proximal gastric cancers (PGCs) in the United States and Europe may offset the benefits of ENLD. PGCs certainly have a worse prognosis than distal tumors, and are associated with a higher incidence of LN metastases.
The rationale for extended lymphadenectomy has been enhanced local control. The clearance of the possible metastatic nodes in the region outside of the perigastric nodes is presumed to impact on overall patient survival rates. The proponents of systemic LND point to numerous anatomical/ lymphographic studies, histopathologic analyses, statistical analyses of LN metastases, clinical prognostic observations, and advances in surgical techniques to support their argument that ELND is the most effective procedure to treat the lymphatic spread to GC
( 1,
6 ).
Roukos's results showed that among all patients who had a D2 dissection with curative intent, 25% had positive extraperigastric N2 nodes. Among patients with node-positive disease, one of two also had positive extraperigastric level 2 nodes. Therefore the risk of residual disease in N2 nodes and fatal relapse among the patients with node-positive disease undergoing D1 dissection with apparently curative intent, is very high, about 50%
( 8,
9,
10,
11,
12,
13,
14,
15 ).
Moreover Roukos affirms that the D2 dissection, performed by experienced surgeons and with a spleen and pancreas preservation, can be performed with the same safety as a D1 procedure. Professor Brennan, in his editorial on the Dutch trial, point out that the patient can only be harmed by an extended lymph node dissection when it is performed by an experienced surgeon
( 8,
16,
17,
18,
19,
20,
21,
22,
23,
24,
25,
26,
27,
28 ).
In Japan the tail and body of the pancreas are generally removed for dissection of lymph nodes along the splenic artery. Furukawa et al describe a pancreas preserving method superior to the more common pancreas resecting method with regard to surgical risk and postoperative glucose tolerance.
Iwanaga et al and Maruyama et al have reported a new dissection method in which the entire pancreas is preserved. The splenic artery is removed at the point just after the branching of the dorsal pancreatic artery, and lymph nodes along the splenic artery are dissected from the surface of the pancreas and splenic vein. The splenic vein is preserved over the length of the whole pancreas o ensure proper blood drainage. The spleen is removed with nodes at the splenic hilum. Both studies reported the feasibility and the lower surgical risk of this technique compared with a total gastrectomy with pancreatosplenectomy method
( 29,
30,
31 ).
Japanese surgeons have been actively performing extended lymphadenectomy (D2, removal of perigastric nodes and nodes along the left gastric, common hepatic, celiac and splenic arteries; or D3, D2 plus removal of nodes in the hepatoduodenal ligament, in the retropancreatic space and along the vessels of the transverse mesocolon). In recent years interest has expanded to superextended lymphadenectomy (D4) of nodes around abdominal aorta (para-aortic lymph nodes from aortic hiatus to aortic bifurcation). Because the therapeutic value of this D4 procedure remains controversial, Maeta et al. initiated a prospective study to compare D3 and D4 lymphadenectomy. Surgical treatment of microscopic disease in grossly normal para-aortic lymph nodes may generate occasional long-term survivors. Selecting appropriate candidates who might benefit from D4 resections needs to be refined
( 32 ).
Natalini et al in a retrospective study of 132 patients who underwent gastrectomy with therapeutic lymphadenectomy for gastric cancer from November 1994 to February 2000 underline that surprisingly the mortality for D1-D2 lymphadenectomy was higher than D3-D4 lymphadenectomy ( 6,8% vs 2,9% ) because of the poor conditions of the patients who were submitted to D1-D2 lymphadenectomy
( 33 ).
Only 10% to 20% of surgical decisions are based on randomized controlled trials, compared with about 30% to 50% of decisions in the field of general medicine. Surgeons should be encouraged to conduct more controlled trials of lymph node dissections and should collaborate with biomedical statisticians. They must give careful consideration to the nature of surgical research, as well as to factors such as the patient's nutritional status, life style, and drug, alcohol, and tobacco use. So-called evidence-based surgery may be a driving force for improving reliability and feasibility of surgical procedures ( 7 ).
References
1) Hong Jin Kim, Martin S Karpeh, Murray F Brennan. Standardization of the extent of lymphadenectomy for gastric cancer: impact on survival. Advances in Surgery, volume 35 2001, 203-223.
2) T Lerut et al. Cancer of the esophagus and gastro-esophageal junction: potentially curative therapies. Surgical Oncology 10 (2001) 113-122.
3) Takaki Yoshikawa et al. Is D2 Lymph Node Dissection Necessary for Early Gastric Cancer? Annals of Surgical Oncology 9:401-405 (2002)
4) Robert C. G. Martin, David P. Jaques, Murray F. Brennan , and Martin Karpeh. Achieving R0 resection for locally advanced gastric cancer: is it worth the risk of multiorgan resection? J Am Coll Surg.194, 5, May 2002, Pages 568-577
5) Onate-Ocana LF et al. Preoperative multivariate prediction of morbidity after gastrectomy for adenocarcinoma. Ann Surg Oncol 2000; 7: 281-288.
6) HJ Meyer, J.Jahne. Lymph node dissection for gastric cancer. Seminars in Surgical Oncology 1999; 17:117-124.
7) Yoshihiko Maehara et al. Therapeutic value of lymph node dissection and the clinical outcome for patients with gastric cancer. Surgery 2002; 131: S 85-91.
8) Roukos DH. Extended (D2) lymph node dissection for gastric cancer: do patients benefit?(editorial) Ann Surg Oncol 2000; 7: 253-5
9) Roukos DH, Lorenz M, Encke A. Evidence of survival benefit of extended (D2) lymphadenectomy in western patients with gastric cancer based on a new concept: a prospective long-term follow-up study. Surgery 1998; 123: 573-8.
10) Dimitrios H. Roukos, and Aggelos M. Kappas. Limitations in Controlling Risk for Recurrence After Curative Surgery for Advanced Gastric Cancer Are Now Well-Explained by Molecular-Based Mechanisms. Ann Surg Oncol 2001 8: 620-621.
11) D. H. Roukos. Current advances and changes in treatment strategy may improve survival and quality of life in patients with potentially curable gastric cancer. Ann Surg Oncol 1999 6: 46-56.
12) D. H. Roukos, P. Paraschou, and M. Lorenz. Distal gastric cancer and extensive surgery: a new evaluation method based on the study of the status of residual lymph nodes after limited surgery. Ann Surg Oncol 2000 7: 719-726.
13) M. J. Heslin. Extended lymph node dissection in gastric cancer: if a benefit exists, can it ever be proven? Ann Surg Oncol 2000 7: 715-716.
14) Katai H et al. Incidence of nodal metatasis around the superior border of the pancreas based on number of metastatic lymph nodes. Gastric Cancer 1998; 1: 115-7.
15) Dimitrios H. Roukos, Mathias Lorenz, Albrecht Encke. Evidence of survival benefit of extended (D2) lymphadenectomy in Western patients with gastric cancer based on a new concept: A prospective long-term follow-up study. Surgery 1998; 123: 573-8.
16) Brennan MF. Lymph-node dissection for gastric cancer (editorial). N Engl J Med 1999; 340: 956-8.
17) Attila Csendes et al. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma. Surgery 2002; 131: 401-407.
18) Kang Young Lee, Sung Hoon Noh, Woo Jin Hyung, Jun Ho Lee, Ki Hyeok Lah, Seung Ho Choi, and Jin Sik Min. Impact of Splenectomy for Lymph Node Dissection on Long-Term Surgical Outcome in Gastric Cancer. Ann Surg Oncol 2001 8: 402-406.
19) Yuichi Kasakura, Masashi Fujii, Fumiro Mochizuki, Mitsugu Kochi and Teruo Kaiga. Is there a benefit of pancreaticosplenectomy with gastrectomy for advanced gastric cancer? 2000; 179: 237-242.
20) K Kitamura et al. No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer. B J S 1999, 86, 119-122.
21) Nick Hayes et al. Total gastrectomy with extended lymphadenectomy for curable stomach cancer: experience in a non-japanese asian center. J Am Coll Surg 1999; 188: 27-32.
22) Y Adachi et al. Morbidity after D2 and D3 gastrectomy for node-positive gastric carcinoma. J Am Coll Surg 1997, 184: 240-244.
23) Harold J Wanebo et al. Role of splenectomy in gastric cancer surgery: adverse effect of elective splenectomy on long term survival. J Am Coll surg 1997; 185: 177-184.
24) Sung Joon Kwon et al. Prognostic impact of splenectomy on gastric cancer: results of the korean gastric cancer study group. WJS 1997: 21, 837-844.
25) Y Kodera et al. Lack of benefit of combined pancreaticosplenectomy in D2 resection for proximal-third gastric carcinoma. WJS 1997: 21, 622-628.
26) Harold O Douglass. Effect of lymph node dissection on survival of gastric carcinoma. J Am Coll Surg 1997: 184,667-668.
27) HJ Wanebo. Commentary. J Am Coll Surg 1997: 184, 668.
28) Jeffrey S Lee and Harold O Douglass Jr. D2 dissection for gastric cancer. Surgical Oncology. 1997, vol 6, n 4, 215-225.
29) H. Furukawa, M. Hiratsuka, O. Ishikawa, M. Ikeda, H. Imamura, S. Masutani, M. Tatsuta, and T. Satomi. Total gastrectomy with dissection of lymph nodes along the splenic artery: a pancreas-preserving method. Ann Surg Oncol 2000 7: 669-673.
30) Iwanaga T et al. Indication and method of total gastrectomy with preserving pancreas and splenectomy for gastric carcinoma. Shokakigeka 1982; 5; 59-67.
31) Maruyama K et al. Pancrea-preserving total gastrectomy for proximal gastric cancer. WJS 1995; 19:532-6.
32) Michio Maeta et al. A prospective pilot study of extended (D3) and superextended para-aortic lymphadenectomy (D4) in patients with T3 or T4 gastric cancer managed by total gastrectomy. Surgery 1999; 125:235-31.
33) G Natalini, F Breccolotto, F Guiggi, R Giuli. Morbidity and mortality of the D3-D4 therapeutic lymphadenectomy for gastric cancer. 4th International Gastric Cancer, New York, NY, 2001, p.881-885.
34) W Lawrence. Extended surgery for gastric cancer. Cancer 1998, volume 82, number 3, 429-432.
35) Igor B Shohepotin et al. Extended surgical resection in T4 gastric cancer. Am J Surg 1998; 175: 123-126.
36) I Kodama et al. Gastrectomy with combined resection of other organs for carcinoma of the stomach with invasion to adjacent organs: clinical efficacy in a retrospective study. J Am Coll Surg 1997, 184: 16-22.
37) Bonnenkamp JJ, Hermans J, Sasako M, van de Velde CJH, et al. Extended lymph-node dissection for gastric cancer. N Engl J Med 1999; 340: 908-14.
38) Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resection for gastric cancer: long-term results of the MRC randomised surgical trial. Surgical co-operation group. Br J Cancer 1999; 79: 1522-30.
39) Emin Yildirim et al. The Turkish experience with curative gastrectomies for gastric carcinoma: is D2 dissection worthwhile? J Am Coll Surg. Volume 192, Issue 1, 2001, 25-37.
40) Volpe CM et al. Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes. Ann Surg Oncol 2000; 7: 139-144.
