Appendix A. Review Search Algorithm

Appendix A. Review Search Algorithm.

1 / exp Stomach Cancer/ or (((gastric or stomach) adj1 cancer$) or ((gastric or stomach) adj1 carcinoma) or ((gastric or stomach) adj1 adenocarcinoma) or ((gastric or stomach) adj1 neoplasm$)).mp.
2 / ((negative or resection) adj2 margin$).mp.
3 / exp frozen section/
4 / exp GASTRECTOMY/
5 / ((gastric or stomach) adj2 resect$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
6 / omentectom$.mp.
7 / multivisceralresection$.mp.
8
9 / (number of lymph nodes or lymph node assessment or lymph node examination or total lymph node count).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]
or/2-7
10 / 1 and 8 and 9
11 / limit 10 to (human and English language)
12 / clinical trial/ or controlled clinical trial/ or exp comparative study/ or meta analysis/ or multicenter study/ or exp practice guideline/ or randomized controlled trial/
13 / 12 and 11
14 / Case Report/
15 / limit 11 to review
16 / 11 not (14 or 15)
17 / 13 or 16
18 / limit 17 to yr="1998 - 2009"
Appendix B. Studies reporting an association between the type of surgical resection performed with the number of lymph nodes assessed
Study / Number of LNs Assessed / Surgical resection (N pts) / Significance
Barbour, 2007 / < 15 LNs: 116 pts (32%) / < D2: 35 (50.7%) ≥ D2: 63 (25.9%)a X: 18 (33.3%) / aP < 0.01
≥ 15 LNs: 250 (68%) / < D2: 34 (49.3%) ≥ D2: 180 (74.1%)a X: 36 (66.7%)
Bouvier, 2002 * / 0 LNs: 87 pts (11.6%) / DG: 50 (11.7%)a PEG: 12 (19.7%)a TG or ETG: 16 (6.3%)a / aP < 0.0001 for DG+PEG vs TG+ETG
1-9 LNs: 359 pts (47.9%) / DG: 220 (51.6%)a PG: 26 (42.6%)a TG or ETG: 112 (44.4%)a
10- 14 LNs: 171 pts (22.8%) / DG: 102 (23.9%)a PG: 15 (24.6%)a TG or ETG: 54 (21.4%)a
≥ 15 LNs: 132 pts (17.6%) / DG: 54 (12.7%)a PG: 8 (13.1%)a TG or ETG: 70 (27.8%)a
Coburn, 2006 / <15 LNs: 7673 pts (71%) / DG: 3599 (33.3%) PG: 2269 (21%) TG: 1675 (15.5%) En Bloc: 1405 (13%) NOS: 1859 (17.2%) / OR (95%CI) of ≥ 15 LNs assessed: En Bloc vs DG: OR = 1.933 (1.671- 2.236) PG vs DG: OR = 1.268 (1.104- 1.457) TG vs DG: OR = 1.854 (1.617- 2.127)
≥ 15 LNs: 3134 pts (29%)
Giuliani, 2004 / 15-26 LNs: 115 pts (74.7%) / DG: 76 (82.6%)a TG: 39 (62.9%)a / aP = 0.006
> 26 LNs: 39 pts (25.3%) / DG: 16 (17.4%)a TG: 23 (37.1%)a
Siewert, 1998 / ≤ 25 LNs: 558 pts (33.7%) / D1: 558 (100%) / P < 0.05
> 25 LNs: 1096 pts (66.3%) / D2: 1096 (100%)
DG = distal gastrectomy; PEG = proximal esophago-gastrectomy; PG = proximal gastrectomy; TG = total gastrectomy; ETG = extended total gastrectomy; STG = sub-total gastrectomy; X = unknown; NOS = not otherwise specified; OR = odds ratio; CI = confidence interval; * = surgical resection type unknown for 10 patients.
Appendix C. Studies reporting an association between tumor location and size with the number of lymph nodes assessed
Study / Number of LNs Assessed / Tumor Location (N pts) / Tumor Size (N pts) / Significance
Barbour, 2007 / < 15 LNs: 116 pts (32%) / Siewert II: 87 (33%)b
Siewert III: 28 (27.5%)b / Md: 4.0 cmc Mn: 4.3 cmc / b,cP = NS
≥ 15 LNs: 250 (68%) / Siewert II: 177 (67%)b
Siewert III: 74 (72.5%)b / Md: 4.5 cmc Mn: 4.7 cmc
Bouvier, 2002 * / 0 LNs: 87 pts (11.6%) / U1/3: 37 (12.5%)b,c
M1/3: 21 (10.4%)b,c
L1/3: 20 (13.2%)b,c
> 1 site: 3 (3.2%)b / < 3 cm: 36 (17.7%)d 3-7 cm: 20 (6.0%)d > 7 cm: 12 (6.3%)d / b,cP < 0.0001 for tumor in 1 site vs two sites and L1/3 vs. M1/3 or U1/3; dP < 0.0001 for tumors < 3 cm vs > 3 cm;
1-9 LNs: 359 pts (47.9%) / U1/3: 143 (48.1%)b,c
M1/3: 89 (44.3%)b,c
L1/3: 80 (52.6%)b,c
> 1 site: 47 (50.5%)b / < 3 cm: 107 (52.7%)d
3-7 cm: 162 (48.6%)d
> 7 cm: 86 (45.3%)d
10- 14 LNs: 171 pts (22.8%) / U1/3: 66 (22.2%)b,c
M1/3: 47 (23.4%)b,c
L1/3: 34 (22.4%)b,c
> 1 site: 24 (25.8%)b / < 3 cm: 35 (17.2%)d 3-7 cm: 84 (25.2%)d > 7 cm: 52 (27.4%)d
≥ 15 LNs: 132 pts (17.6%) / U1/3: 51 (17.2%)b,c
M1/3: 44 (21.9%)b,c
L1/3: 18 (11.8%)b,c
> 1 site: 19 (20.4%)b / < 3 cm: 25 (12.3%)d 3-7 cm: 67 (20.1%)d > 7 cm: 40 (21.1%)d
Giuliani, 2004 / 15-26 LNs: 115 pts (74.7%) / U1/3: 15 (78.9%)b
M1/3: 18 (56.3%)b
L1/3: 82 (79.6%)b / < 2.6 cm: 47 (82.5%)c
2.6-5.0 cm: 42 (76.4%)c
> 5.0 cm: 26 (61.9%)c / bP = 0.027 cP = 0.023
> 26 LNs: 39 pts (25.3%) / U1/3: 4 (21.1%)b
M1/3: 14 (43.7%)b
L1/3: 21 (20.4%)b / < 2.6 cm: 10 (17.5%)c
2.6-5.0 cm: 13 (23.6%)c
> 5.0 cm: 16 (38.1%)c
Liu, 2003 / ≤15 LNs: 124 pts (84.4%) / P: 44 (35%)a
M/D: 58 (47%)a
L/U: 22 (18%)a / NR / aP = NS
> 15 LNs: 23 pts (15.6%) / P: 13 (57%)a
M/D: 7 (30%)a
L/U: 3 (13%)a
Liu, 2009 / < 15 LNs: 208 pts (53.1%) / U1/3: 52 (78.8%)a
M1/3: 36 (57.1%)a
L1/3: 110 (44.7%)a
Total: 10 (58.8%)a / NR / aP < 0.0001
15- 25 LNs: 125 pts (31.9%) / U1/3: 11 (16.7%)a
M1/3: 19 (30.2%)a
L1/3: 92 (37.4%)a
Total: 3 (17.7%)a
> 25 LNs: 59 pts (15.1%) / U1/3: 3 (4.6%)a
M1/3: 8 (12.7%)a
L1/3: 44 (17.9%)a
Total: 4 (23.5%)a
Shen, 2007 / ≤ 30 LNs: 432 (22.8%) / U1/3: 67 (22.2%)a
M1/3: 168 (22.3%)a
L1/3: 188 (24.0%)a
Dif: 2 (6.7%)a
X: 7 (24.1%)a / Mn: 5.3 cmb / aP = NS bP < 0.001
>30 LNs: 1463 (77.2%) / U1/3: 234 (77.7%)a
M1/3: 585 (77.7%)a L1/3: 594 (76.0%)a
Dif: 28 (93.3%)a
X: 22 (75.9%)a / Mn: 5.9 cmb
Siewert, 1998 / ≤ 25 LNs: 558 pts (33.7%) / U1/3: 172 (34.7%)a
M1/3: 194 (30.2%)a L1/3: 175 (40.2%)a
Total: 17 (21.3%)a / NR / aP = NS
> 25 LNs: 1096 pts (66.3%) / U1/3: 324 (65.3%)a
M1/3: 449 (69.8%)a L1/3: 260 (59.8%)a
Total: 63 (78.7%)a
U1/3 = upper third; M1/3 = middle third; L1/3 = lower third; D = distal; non-D = non-distal; L/U = Linitis/Unspecififed; Dif = diffuse; X = unknown; OR = odds ratio; CI = confidence interval; * = tumor location unknown for 6 patients and tumor size unknown for 21 patients.
Appendix D. Studies reporting an association between cancer stage and the number of lymph nodes assessed
Study / Number of LNs Assessed / Staging (N pts) / Significance
Barbour, 2007 / < 15 LNs: 116 pts (32%) / T1: 24 (32.9%)d T2: 29 (31.2%)e T3: 60 (30.6%)f T4: 2 (50%)g / N0: 53 (36.8%)h N1: 50 (33.3%)i N2: 12 (21.8%)j N3: 0%k / I: 40 (35.7%)l II: 25 (31.3%)m III: 48 (31.4%)n IV: 2 (9.5%)o / kP < 0.01 d,e,f,g,i,j,l,m,nP = NS hP = 0.08 oP = 0.03
≥ 15 LNs: 250 (68%) / T1: 49 (67.1%)d T2: 64 (68.8%)e T3: 136 (69.4%)f T4: 2 (50%)g / N0: 91 (63.2%)h N1: 100 (66.7%)i N2: 43 (78.2%)j N3: 17 (100%)k / I: 72 (64.3%)l II: 55 (68.7%)m III: 105 (68.6%)n IV: 19 (90.5%)o
Bouvier, 2002 * / 0 LNs: 87 pts (11.6%) / T1: 13 (14.0%)e T2: 10 (13.2%)e T3: 39 (9.2%)e T4: 13 (9.0%)e / eP < 0.05 for T1/ T2 vs T3/T4
1-9 LNs: 359 pts (47.9%) / T1: 54 (58.1%)e T2: 39 (51.3%)e T3: 207 (48.9%)e T4: 59 (40.7%)e
10- 14 LNs: 171 pts (22.8%) / T1: 14 (15.1%)e T2: 15 (19.7%)e T3: 106 (25.1%)e T4: 36 (24.8%)e
≥ 15 LNs: 132 pts (17.6%) / T1: 12 (12.9%)e T2: 12 (15.8%)e T3: 71 (16.8%)e T4: 37 (25.5%)e
Coburn, 2006 # / <15 LNs: 7673 pts (71%) / T2 vs T1: OR = 1.347 (1.115-1.627)
T3 vs T1: OR = 1.581 (1.350-1.851)
T4 vs T1: OR = 1.576 (1.358-1.829) / _
≥ 15 LNs: 3134 pts (29%)
Giuliani, 2004 / 15-26 LNs: 115 pts (74.7%) / T1: 32 (84.2%)d T2: 76 (74.5%)d T3: 7 (50%)d / dP = NS
> 26 LNs: 39 pts (25.3%) / T1: 6 (15.8%)d T2: 26 (25.5%)d T3: 7 (50%)d
Huang, 2008 / < 15 LNs: 36 pts (15.3%) / T2: 25 (10.6%)a T3: 118 (50%)a T4: 93 (39.4%)a / aP = NS
15-19 LNs: 43 pts (18.2%)
20-24 LNs: 62 pts (26.3%)
25-29 LNs: 40 pts (16.9%)
≥ 30 LNs: 55 pts (23.3%)
Lee, 2001 / < 15 LNs: 424 pts (9.9%) / T1: 180 (12.7%)a T2: 122 (8.5%)b T3: 122 (8.6%)c / a,b,cP < 0.05
15-29 LNs: 1826 (42.8%) / T1: 649 (45.9%)a T2: 553 (38.5%)b T3: 624 (43.9%)c
≥ 30 LNs: 2020 pts (47.3%) / T1: 584 (41.3%)a T2: 762 (53.0%)b T3: 674 (47.5%)c
Liu, 2003 / ≤15 LNs: 124 pts (84.4%) / T1: 19 (90.5%)b T2a/b: 41 (89.1%)b T3: 49 (76.6%)b T4: 12 (92.3%)b / N0: 45 (91.8%)c N1: 51 (86.4%)c N2: 28 (82.4%)c N3: 0 (0%)c M0: 112 (84.2%)d M1:12 (85.7%)d / IA: 15 (88.2%)e IB: 22 (100%)e II: 25 (89.3%)e
IIIA: 21 (80.8%)e
IIIB: 17 (77.3%)e
IV: 21 (72.4%)e / dP = NS bP = 0.005 c,eP < 0.0001
> 15 LNs: 23 pts (15.6%) / T1: 2 (9.5%)b T2a/b: 5 (10.9%)b T3: 15 (23.4%)b T4: 1 (7.7%)b / N0: 4 (8.2%)c N1: 8 (13.6%)c N2: 6 (17.6%)c N3: 5 (100%)c M0: 21 (15.8%)d M1:2 (14.3%)d / IA: 2 (11.8%)e
IB: 0 (0%)e
II: 3 (10.7%)e
IIIA: 5 (19.2%)e
IIIB: 5 (22.7%)e
IV: 8 (27.6%)e
Liu, 2009 / < 15 LNs: 208 pts (53.1%) / T2b; 100%
N0: 89 (66.4%)b N1: 108 (55.4%)b N2: 11 (21.6%)b N3: 0%b / bP < 0.001
15- 25 LNs: 125 pts (31.9%) / T2b: 100%
N0: 31 (23.1%)b N1: 61 (31.3%)b N2: 28 (54.9%)b N3: 5 (41.7%)b
> 25 LNs: 59 pts (15.1%) / T2b: 100%
N0: 14 (10.5%)b N1: 26 (13.3%)b N2: 12 (23.5%)b N3: 7 (58.3%)b
Shen, 2007 / ≤ 30 LNs: 432 (22.8%) / N0: 121 (26.3%)c N1: 195 (28.4%)c N2: 96 (22.1%)c N3: 20 (6.4%)c / cP < 0.001
>30 LNs: 1463 (77.2%) / N0: 339 (73.7%)c N1: 492 (71.6%)c N2: 339 (77.9%)c N3: 293 (93.6%)c
Siewert, 1998 / ≤ 25 LNs: 558 pts (33.7%) / T1: 116 (41.6%)b T2: 215 (35.5%)b T3: 197 (30.8%)b T4: 30 (22.9%)b / N0: 216 (40.3%)c N1: 167 (45.9%)c N2: 175 (23.2%)c M0: 403 (34.4%)d M1: 155 (32.0%)d / IA: 99 (%)e IB: 84 (%)e II: 89 (%)e IIIA: 85 (%)e IIIB: 44 (%)e IV: 157 (%)e / b,d,eP = NS cP < 0.001
> 25 LNs: 1096 pts (66.3%) / T1: 163 (58.4%)b T2: 390 (64.5%)b T3: 442 (69.2%)b T4: 101 (77.1%)b / N0: 320 (59.7%)c N1: 197 (54.1%)c N2: 579 (76.8%)c M0: 767 (65.6%)d M1: 329 (68.0%)d / IA: 130 (%)e IB: 137 (%)e II: 141 (%)e IIIA: 177 (%)e IIIB: 160 (%)e IV: 351 (%)e
Smith, 2005 / 1-9 LNs: 2143 pts (56.5%) / T1/2N0: 560 (58.8%)a T1/2N1: 184 (52.0%)a
T3N0: 528 (58.1%)a T3N1: 871 (55.2%)a / aP = 0.0013
10-19 LNs: 1153 pts (30.4%) / T1/2N0: 269 (28.2%)a T1/2N1: 124 (35.0%)a
T3N0: 261 (28.7%)a T3N1: 499 (31.6%)a
20-29 LNs: 215 pts (5.7%) / T1/2N0: 49 (5.1%)a T1/2N1: 31 (8.8%)a
T3N0: 47 (5.2%)a T3N1: 88 (5.6%)a
30-39 LNs: 215 pts (5.7%) / T1/2N0: 61 (6.4%)a T1/2N1: 4 (1.1%)a
T3N0: 58 (6.4%)a T3N1: 92 (5.8%)a
> 40 LNs: 67 pts (1.8%) / T1/2N0: 14 (1.5%)a T1/2N1: 11 (3.1%)a
T3N0: 14 (1.5%)a T3N1: 28 (1.8%)a
OR = odds ratio; CI = confidence interval; * = T stage unknown for 12 patients; # = includes only nonmetastatic cases (T4N1-3 and T1-3N3);
Appendix E. Clinical stage survival rates associated with the number LN assessed.
Study / N / Stage I / Stage II / Stage III / Stage IV / Significance
Bouvier[35] / NR / < 10 LNs vs ≥ 10 LNs: aP = 0.001 bP < 0.05
RR is for Stg I and II only
≥ 10 LNs: 132 pts (17.6%) / RR (95%CI) of death: 0.58b
Coburn[27] / <15 LNs: 7673 pts (71%) / P < 0.0001 for <15 LNs vs ≥15 LNs assessed in all stages I, II, III, IV# / _
≥ 15 LNs: 3134 pts (29%)
Huang [39] / < 15 LNs: 36 pts (15.3%) / 7-14 vs ≥ 15 LNs: II: P = NS III: P < 0.0001 IV: P = 0.0369 / _
15-19 LNs: 43 pts (18.2%) / ≤ 19 vs ≥ 20 LNs: II: P = 0.0136 III: P < 0.0001 IV: P = 0.0032
20-24 LNs: 62 pts (26.3%) / ≤ 24 vs ≥ 25 LNs: II: P = NS III: P < 0.0001 IV: P = 0.0026
25-29 LNs: 40 pts (16.9%) / ≤ 29 vs ≥ 30 LNs: II: P = NS III: P = 0.0032 IV: P = 0.0002
≥ 30 LNs: 55 pts (23.3%) / _
Hundahl[41] / 1 LN: NR / 5-y IA: 78% 5-y IB: 58% / 5-y II: 34% / 5-y IIIA: 20% 5-y IIIB: 8% / 5-y IV: 7% / NR
1-6 LNs: 25% / 5-y IA: 75% 5-y IB: 48% / 5-y II: 26% / 5-y IIIA: 14% 5-y IIIB: - / 5-y IV: 6%
7-15 LNs: 31% / 5-y IA: 81% 5-y IB: 60% / 5-y II: 34% / 5-y IIIA: 20% 5-y IIIB: 6% / 5-y IV: 6%
≥ 15 LNs: 18% / 5-y IA: 79% 5-y IB: 68% / 5-y II: 44% / 5-y IIIA: 25% 5-y IIIB: 10% / 5-y IV: 8%
≥ 25 LNs: NR / 5-y IA: 79% 5-y IB: 68% / 5-y II: 44% / 5-y IIIA: 22% 5-y IIIB: 19% / 5-y IV: 9%
Ichikura[30] / 1-4 LNs: 8 pts (0.86%) / NR / fP = 0.002 gP = 0.04 hP = NS
5-9 LNs: 45 pts (4.9%) / IA: 3-y = 92%f ; 5-y = 92%f / NR
10-14 LNs: 58 pts (6.3%) / 10-19 LN: IA: 3-y = 96%; 5-y = 92% IB: 3-y = 86% ; 5-y = 86% / 10- 19 LNs: II: 3-y = 79%; 5-y = 79% / 10- 19 LNs: III: 3-y = 47%g ; 5-y = 27%g / NR
15-19 LNs: 102 pts (11.0%)
20-29 LNs: 244 pts (26.4%) / IA: 3-y = 97%; 5-y = 94% IB: 3-y = 93%; 5-y = 90% / II: 3-y = 78%; 5-y = 72% / III: 3-y = 58%h ; 5-y = 42%h / NR
> 30 LNs: 468 pts (50.6%) / IA: 3-y = 99%f ; 5-y = 97%f IB: 3-y = 95%; 5-y = 95% / II: 3-y = 82%;
5-y= 74% / III: 3-y = 61%g,h ; 5-y = 54%g,h / IV: 3-y 24%; 5-y = 14%
Karpeh[18] / < 15 LNs: 286 pts (27.6%) / 5-y IA: 90% 5-y IB: 83% / 5-y II: 30% / 5-y IIIA: 19%c 5-y IIIB: 4%c / 5-y IV: 2%c / cP < 0.001
≥ 15 LNs: 752 pts (72.4%) / 5-y IA: 95% 5-y IB: 85% / 5-y II: 54% / 5-y IIIA: 37%c 5-y IIIB: 11%c / 5-y IV: 7%c
Lee [29] / < 15 LNs: 435 pts (9.1%) / 5-y IA: 93% 5-y IB: 75% / 5-y II: 57% / 5-y IIIA: 26%a 5-y IIIB: 30% / NR / aP < 0.001
≥ 15 LNs: 4354 pts (90.9%) / 5-y IA: 93% 5-y IB: 85% / 5-y II: 69% / 5-y IIIA: 53% 5-y IIIB: 31% / 5-y IV:18%
Liu [44] / ≤15 LNs assessed: 124 pts / Md I+II: 5.6 yd / 5-y III: 9%c Md III: 1.2 ye / Md IV: 0.55 yf / d,fP = NS c,eP = 0.006
> 15 LNs assessed: 23 pts / Md I+II: 2.4 yd / 5-y III: 46%c Md III: 2.82 ye / Md IV: 0.36 yf
Siewert[3] / ≤ 25 LNs: 558 pts (33.7%) / IA: 5-y = 81.4%m; 10-y = 73.9%m IB: 5-y = 68.6%n; 10-y = 49.6%n / II: 5-y = 29.2%o; 10-y = 19.9%o / IIIA: 5-y = 24.3%p; 10-y = 17%p IIIB: 5-y = 20%q; 10-y = 12%q / IV: 5-y = 21.7%r; 10-y = 14.5%r / m,n,q,rP = NS oP < 0.001 pP = 0.035
> 25 LNs: 1096 pts (66.3%) / IA: 5-y = 84.3%m; 10-y = 70.1%m IB: 5-y = 68%n; 10-y = 53.2%n / II: 5-y = 56.7%o; 10-y = 49.2%o / IIIA: 5-y = 32.1%p; 10-y = 17.4%p IIIB: 5-y = 13.5%q; 10-y = 10.1%q / IV: 5-y = 12.9%r; 10-y = 8.9%r
Volpe [49] / < 15 LNs: 52 pts (46%) / NR / 5-y II: 9%c 5-y II with limited dissection: 11%d / NR / NR / cP = 0.005 dP = 0.01
≥ 15 LNs: 62 pts (54%) / 5-y II: 50%c 5-y II with extended dissection: 57%d
LN = lymph node; Md = median; RR = relative risk; CI = confidence interval; NR = not reported; NS = not significant; # = includes only non-metastatic cases (T4N1-3 and T1-3N3).