A decade in gastric cancer curative surgery: Evidence of progress (1999-2009)

Table 1 Sackett's classification of the level of evidence according to the modification of Heinrich et al[10,11]

Level of evidence	Type of trial	Criteria for classification	Grade of recommendation
I	Large randomized trials with clear-cut results (and low error risk)	Sample size calculation provided and fulfilled; study endpoint provided	A
II	Small randomized trials with uncertain results (and moderate to high error risk)	Matched analysis, sample size calculation not given or not fulfilled; study endpoints not provided; convincing comparative studies	B
III	Nonrandomized, contemporaneous controls	Noncomparative, prospective	C
IV	Nonrandomized, historical controls	Retrospective analysis, cohort studies	-
V	V No control, case series only; experts opinions	Small series, review articles	-

Table 2 Current grade I A recommendations for non-metastatic gastric cancer surgery

Topic	Recommendation	Ref.
Traditional controversies
Extension of resection	Subtotal gastrectomy with 5 cm negative margins is sufficient for the curative treatment of distal tumors	[1]
	Prophylactic splenectomy is not necessary for cardia tumors either	[25-27]
Extension of lymphadenectomy	D2 nodal dissection with spleno-pancreasectomy does not provide any survival benefit and increases post-operative morbidity and mortality rates	[2-3]
	Pancreas-preserving D2 nodal dissection increases survival rates without any significant post-operative morbidity and mortality	[44]
	Para-aortic nodal dissection (in addition to D2 lymphadenectomy) does not improve the survival rate in curable diasease	[45]
Surgery in multimodal strategy
Pre-operative chemotherapy	Pre-operative chemotherapy is associated to an increase in survival rates	[121,122]

Table 3 Ongoing phase-III RCTs concerning non-metastatic gastric cancer surgery (from the trials registry of the United States National Institutes of Health; http://www.clinicaltrial.gov)

Topic	Title of trial	Institution	Estimated enrollment	Study start year	Registration identifier
Traditional controversies
Extension of resection	GCSSG-SPNX: Trial to Evaluate Splenectomy in Total Gastrectomy for Proximal Gastric Carcinoma: JCOG0110	Japan Clinical Oncology Group-Japan	500	2002	NCT00112099[28]
Extension of lymphadenectomy	A Comparison Between D1 and D2 Lymphadenectomy in Gastric Cancer: A Prospective Randomized Controlled Trial	Tata Memorial Hospital-India	600	2007	NCT00447746[46]
Minimally invasive approach
Laparoscopic resection	Prospective Randomized Trial of Laparoscopy-Assisted Distal Gastrectomy (LADG) Versus Open Distal Gastrectomy (ODG) in Patients With Early Gastric Cancer (EGC)	National Cancer Center-Korea	164	2003	NCT00546468[100]
	Multi-Institutional Prospective Randomized Trial on the Assessment of Laparoscopic Surgery for Gastric Cancer	National Cancer Center-Korea	1400	2006	NCT00452751[101]
Surgery in multimodal strategy
Pre-operative chemotherapy	Randomized Phase III Trial of Surgery Plus Neoadjuvant TS-1 and Cisplatin Compared With Surgery Alone for Type 4 and Large Type 3 Gastric Cancer: Japan Clinical Oncology Group Study (JCOG 0501)	Japan Clinical Oncology Group-Japan	316	2005	NCT00252161[123]
	A Multicenter Randomized Phase III Trial of Neo-Adjuvant Chemotherapy Followed by Surgery and Chemotherapy or by Surgery and Chemoradiotherapy in Resectable Gastric Cancer (CRITICS Study)	Dutch Colorectal Cancer Group-Netherlands	788	2006	NCT00407186[125]
	A Randomized Controlled Phase II/III Trial of Peri-Operative Chemotherapy With or Without Bevacizumab in Operable Adenocarcinoma of the Stomach and Gastro Oesophageal Junction	Medical Research Council-United Kingdom	1100	2007	NCT00450203[124]