Retrospective Study
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World J Gastrointest Pathophysiol. Apr 22, 2024; 15(1): 91237
Published online Apr 22, 2024. doi: 10.4291/wjgp.v15.i1.91237
Table 1 Tumor budding, desmoplastic reaction and tumor-infiltrating lymphocytes in relation to clinicopathological parameters in the whole group
Parameters n PTB1 (%) PTB2 (%) PTB3 (%) ITB1 (%) ITB2 (%) ITB3 (%) DR1 (%) DR2 (%) DR3 (%) TILs (%) TILs (%) Age, yr < 62.14 ± 12.00 64 11 (42.3) 25 (59.5) 28 (45.2) 15 (48.4) 14 (56.0) 35 (47.3) 29 (50.0) 20 (52.6) 15 (44.1) 34 (50.0) 30 (48.4) ≥ 62.14 ± 12.00 66 15 (57.7) 17 (40.5) 34 (54.8) 16 (51.6) 11 (44.0) 39 (52.7) 29 (50.0) 18 (47.4) 19 (55.9) 34 (50.0) 32 (51.6) Gender Male 77 16 (61.5) 26 (61.9) 35 (56.5) 18 (58.1) 19 (76.0) 40 (54.1) 43 (74.1) 23 (60.5) 11 (32.4)a 36 (52.9) 41 (66.1) Female 53 10 (38.5) 16 (38.1) 27 (43.5) 13 (41.9) 6 (24.0) 34 (45.9) 15 (25.9) 15 (39.5) 23 (67.6) 32 (47.1) 21 (33.9) Diameter < 1.86 ± 1.02 84 16 (61.5) 29 (69.0) 39 (62.9) 16 (51.6) 19 (76.0) 49 (66.2) 34 (58.6) 28 (73.7) 22 (64.7) 47 (69.1) 37 (59.7) ≥ 1.86 ± 1.02 46 10 (38.5) 13 (31.0) 23 (37.1) 15 (48.4) 6 (24.0) 25 (33.8) 24 (41.4) 10 (26.3) 12 (35.3) 21 (30.9) 25 (40.3) Invasion T1 7 5 (19.2) 2 (4.8) 0b 4 (12.9) 1 (4.0) 2 (2.7) 3 (5.2) 3 (7.9) 1 (2.9) 4 (5.9) 3 (4.8) T2 39 4 (15.4) 15 (35.7) 20 (32.3) 12 (38.7) 8 (32.0) 19 (25.7) 22 (37.9) 9 (23.7) 8 (23.5) 18 (26.5) 21 (33.9) T3 52 11 (42.3) 15 (35.7) 26 (41.9) 10 (32.3) 6 (24.0) 36 (48.6) 25 (43.1) 16 (42.1) 11 (32.4) 27 (39.7) 25 (40.3) T4 32 6 (23.1) 10 (23.8) 16 (25.8) 5 (16.1) 10 (40.0) 17 (23.0) 8 (13.8) 10 (26.3) 14 (41.2) 19 (27.9) 13 (21.0) LNM Absent 82 23 (88.5) 29 (69.0) 30 (48.4)a 29 (93.5) 16 (64.0) 37 (50.0)a 43 (74.1) 23 (60.5) 16 (47.1)c 38 (55.9) 44 (71.0) Present 48 3 (11.5) 13 (31.0) 32 (51.6) 2 (6.5) 9 (36.0) 37 (50.0) 15 (25.9) 15 (39.5) 18 (52.9) 30 (44.1) 18 (29.0) Metastasis Absent 106 26 (100.0) 31 (73.8) 49 (79.0)c 21 (67.7) 23 (92.0) 62 (83.8) 49 (84.5) 33 (86.8) 24 (70.6) 55 (80.9) 51 (82.3) Present 24 - 11 (26.2) 13 (21.0) 10 (32.3) 2 (8.0) 12 (16.2) 9 (15.5) 5 (13.2) 10 (29.4) 13 (19.1) 11 (17.7) Stage I 21 11 (42.3) 9 (21.4) 1 (1.6)a 10 (32.3) 6 (24.0) 5 (6.8)a 13 (22.4) 6 (15.8) 2 (5.9) 13 (19.1) 8 (12.9) II 38 6 (23.1) 12 (28.6) 20 (32.3) 8 (25.8) 4 (16.0) 26 (35.1) 20 (34.5) 11 (28.9) 7 (20.6) 18 (26.5) 20 (32.3) III 48 8 (30.8) 11 (26.2) 29 (46.8) 3 (9.7) 14 (56.0) 31 (41.9) 16 (27.6) 15 (39.5) 17 (50.0) 24 (35.3) 24 (38.7) IV 23 1 (3.8) 10 (23.8) 12 (19.4) 10 (32.3) 1 (4.0) 12 (16.2) 9 (15.5) 6 (15.8) 8 (23.5) 13 (19.1) 10 (16.1) Subtype Intestinal 100 24 (92.4) 39 (92.9) 37 (59.7)a 30 (96.8) 21 (84.0) 49 (66.2)b 47 (81.0) 28 (73.7) 25 (73.5) 52 (76.5) 48 (77.4) Diffuse 19 1 (3.8) 3 (7.1) 15 (24.2) 1 (3.2) 2 (8.0) 16 (21.6) 8 (13.8) 4 (10.5) 7 (20.6) 10 (17.7) 9 (14.5) Mixed 11 1 (3.8) 0 10 (16.1) 0 2 (8.0) 9 (12.2) 3 (5.2) 6 (15.8) 2 (5.9) 6 (8.8) 5 (8.1) LVI Absent 89 14 (53.8) 28 (66.7) 47 (75.8) 16 (51.6) 19 (76.0) 54 (73.0) 39 (67.2) 24 (63.2) 26 (76.5) 45 (66.2) 44 (71.0) Present 41 12 (46.2) 14 (33.3) 15 (24.2) 15 (48.4) 6 (24.0) 20 (27.0) 19 (32.8) 14 (36.8) 8 (23.5) 23 (33.8) 18 (29.0) PNI Absent 94 16 (61.5) 28 (66.7) 50 (80.6) 18 (58.1) 19 (76.0) 57 (77.0) 43 (74.1) 25 (65.8) 26 (76.5) 52 (76.5) 42 (67.7) Present 36 10 (38.5) 14 (33.3) 12 (19.4) 13 (49.0) 6 (24.0) 11 (23.0) 15 (25.9) 13 (34.2) 8 (23.5) 16 (23.5) 20 (32.3) Survival Deceased 100 9 (34.6) 29 (69.0) 62 (100.0)a 8 (25.8) 20 (80.0) 72 (97.3)a 40 (69.0) 29 (76.3) 31 (91.2) 56 (82.4) 44 (71.0) Alive 30 17 (65.4) 13 (31.0) 0 23 (74.2) 5 (20.0) 2 (2.7) 18 (31.0) 9 (23.7) 3 (8.8) 12 (17.6) 18 (29.0) PTB PTB1 26 - - - 17 (54.8) 3 (12.0) 6 (8.1)a 15 (25.9) 8 (21.1) 3 (8.8)d 10 (14.7) 16 (25.8)b PTB2 42 - - - 14 (45.2) 18 (72.0) 10 (13.5) 24 (41.4) 12 (31.6) 6 (17.7) 17 (25.0) 25 (40.3) PTB3 62 - - - 0 4 (16.0) 58 (78.4) 19 (32.8) 18 (47.4) 25 (73.5) 41 (60.3) 21 (33.9) ITB ITB1 31 - - - - - - 21 (36.2) 8 (21.1) 2 (5.9)d 9 (13.2) 22 (35.5)d ITB2 25 - - - - - - 13 (22.4) 6 (15.8) 6 (17.6) 13 (19.2) 12 (19.4) ITB3 74 - - - - - - 24 (41.4) 24 (63.2) 26 (76.5) 46 (67.6) 28 (45.1) DR DR1 58 - - - - - - - - - 22 (32.4) 36 (58.0)b DR2 38 - - - - - - - - - 24 (35.2) 14 (22.6) DR3 34 - - - - - - - - - 22 (32.4) 12 (19.4)
Table 2 Clinicopathological parameters associated with survival in all cases and patients with intestinal tumors (Log-rank test)
Parameters All cases Intestinal tumors mean ± SE (95%CI) Median ± SE (95%CI) mean ± SE (95%CI) Median ± SE (95%CI) Age < 62.14 ± 12.00 48.2 ± 4.5 (39.4-56.9) 37.0 ± 1.1 (34.8-39.1) 53 ± 5.9 (41.4-64.5) 36.0 ± 1.2 (33.4-38.5) ≥ 62.14 ± 12.00 50.8 ± 4.8 (41.3-60.3) 39.0 ± 9.5 (20.1-57.8) 55.7 ± 5.7 (44.4-66.9) 60.0 ± 16.2 (28.2-91.7) Gender Male 50.1 ± 4.7 (41.3-59.0) 36.0 ± 2.6 (30.8-41.1) 54.7 ± 5.5 (43.7-65.6) 38.0 ± 3.3 (31.5-44.5) Female 44.9 ± 5.2 (39.1-58.7) 38.0 ± 1.6 (34.9-41.0) 54.5 ± 6.3 (42-67.1) 38.0 ± 9.6 (19.1-56.8) Diameter < 1.86 ± 1.02 47.3 ± 3.7 (40.0-54.6) 38.0 ± 1.8 (3.4-41.5) 50.2 ± 4.5 (41.3-59.1) 38.0 ± 2.7 (32.6-43.3) ≥ 1.86 ± 1.02 52.3 ± 6.3 (39.8-64.7) 36.0 ± 4.6 (26.8-45.1) 61.4 ± 8.2 (45.2-77.6) 38.0 ± 13.4 (11.6-64.3) Invasion T1 65.1 ± 7.1 (51.2-79.1) 78.0 ± 22.1 (34.5-121.4) 65.1 ± 7.1 (51.1-79.1) 78.0 ± 22.1 (34.5-121.4) T2 54.5 ± 6.6 (41.5-67.5) 38.0 ± 2.6 (32.9-43.0) 63.5 ± 8.6 (46.6-80.4) 52.0 ± 14.4 (23.7-80.2) T3 44.8 ± 4.8 (35.4-54.3) 36.0 ± 4.3 (27.5-44.5) 46.4 ± 5.7 (35-57.7) 35.0 ± 5.5 (241.0-45.8) T4 44.0 ± 5.4 (32.3-53.6) 30.0 ± 2.8 (24.4- 35.5) 48.7 ± 7.0 (35-62.5) 36.0 ± 3.1 (29.7-42.2) LNM Absent 51.6 ± 4.8 (52.1-71.0) 46.0 ± 5.5 (35.1-56.8)a 66.1 ± 5.5 (55.3-77.1) 62.0 ± 13.2 (35.8-88.1)a Present 30.6 ± 3.0 (24.6-36.6) 24.0 ± 2.2 (19.5-28.4) 32.1 ± 4.5 (23.3-40.8) 24.0 ± 7.7 (8.7-39.2) Metastasis Absent 48.3 ± 3.2 (41.9-54.8) 38.0 ± 1.5 (34.9-41.0) 53.4 ± 4.1 (45.2-61.6) 39.0 ± 4.8 (29.4-48.5) Present 51.7 ± 9.7 (32.6-70.7) 24.0 ± 8.3 (7.6-40.3) 55.1 ± 10.8 (33.8-76.5) 36.0 ± 12.0 (12.4-59.5) Stage I 69.1 ± 6.9 (55.5-82.7) 72.0 ± 11.1 (50.3-93.6)b 71.5 ± 6.8 (58.1-85.1) 72.0 ± 10.9 (50.5-93.4)c II 45.1 ± 5.3 (34.7-55.5) 37.0 ± 2.2 (32.6-41.3) 52.3 ± 7.2 (38.1-66.5) 39.0 ± 2.5 (34.0-43.9) III 38.6 ± 3.9 (30.8-46.4) 33.0 ± 3.4 (26.2-39.7) 40.0 ± 5.8 (28.5-51.4) 29.0 ± 4.9 (19.2-38.7) IV 31.3 ± 10.8 (37.1-59.5) 30.0 ± 12.3 (11.8-60.1) 38.3 ± 10.8 (27.1-48.7) 30.0 ± 12.3 (29.8-42.1) Subtype Intestinal 55.1 ± 4.4 (46.6-63.7) 38.0 ± 2.7 (32.9-42.1)d - - Not intestinal 32.5 ± 2.2 (18.8-36.7) 30.0 ± 1.2 (6.2-17.7) - - Grade Low - - 61.9 ± 5.7 (50.6-73.2) 52.0 ± 11.6 (29.1-74.8) Moderate - - 49.9 ± 10.6 (29.0-70.8) 32.0 ± 4.7 (22.7-41.2) High - - 43.2 ± 6.8 (29.9-56.5) 29.0 ± 12.3 (4.7-53.2) LVI Absent 54.3 ± 5.8 (43.0-65.7) 41.0 ± 2.2 (36.5-45.4) 59.0 ± 6.9 (45.4-72.7) 41.0 ± 7.0 (27.0-54.9) Present 46.6 ± 4.0 (38.6-54.6) 36.0 ± 3.4 (29.1-42.8) 51.4 ± 5.1 (41.2-61.5) 36.0 ± 2.9 (30.2-41.7) PNI Absent 55.2 ± 6.5 (42.5-67.9) 38.0 ± 3.9 (30.2-45.7) 60.4 ± 7.7 (45.3-75.5) 38.0 ± 9.8 (18.6-57.3) Present 46.9 ± 3.8 (39.4-54.4) 36.0 ± 2.2 (31.6-40.3) 51.7 ± 4.8 (42.3-61.2) 38.0 ± 2.5 (33-42.9) PTB PTB1 88.3 ± 5.2 (78.0-98.6) 73.5 ± 12.7 (71.6-92.5)a 92.4 ± 4.7 (83.3-101.9) 88.2 ± 7.6 (56.9-91.6)a PTB2 61.8 ± 6.4 (48.6-73.6) 38.0 ± 2.8 (33.5-42.5) 63.0 ± 6.5 (50.2-75.8) 41.0 ± 3.1 (34.8-47.1) PTB3 26.7 ± 2.4 (21.9-31.5) 22.0 ± 1.5 (19.1-24.9) 22.7 ± 3.6 (15.6-29.8) 16.0 ± 2.1 (33.8-42.1) ITB ITB1 101.1 ± 6.7 (87.8-114.4) 91.2 ± 5.2 (81.4-112.5)a 103.8 ± 6.4 (91.1-116.4) 63.0 ± 8.3 (88.7-97.4)a ITB2 47.7 ± 4.6 (38.6-56.7) 41.0 ± 4.2 (32.8-49.2) 50.1 ± 5.2 (39.9-60.2) 42.0 ± 6.3 (29.0-52.9) ITB3 29.9 ± 2.4 (25.3-34.6) 26.0 ± 1.9 (22.2-29.8) 28.5 ± 3.4 (21.8-35.2) 22.0 ± 4.0 (13.9-30.0) DR DR1 60.4 ± 5.4 (49.8-70.9) 41.0 ± 7.9 (25.4-56.6)d 67.2 ± 6.2 (55.1-79.3) 72.0 ± 18.1 (36.4-107.5)a DR2 48.0 ± 6.6 (35.1-61.0) 36.0 ± 4.5 (27.3-44.8) 53.5 ± 8.4. (36.9-70.1) 38.0 ± 9.1 (20.0-55.9) DR3 27.0 ± 4.1 (18.8-35.2) 18.0 ± 3.6 (10.8-25.1) 31.8 ± 5.3 (21.3-42.2) 24.0 ± 6.7 (10.9-37.0) TILs TILs 53.8 ± 4.3 (45.3-62.4) 39.0 ± 4.8 (29.4-48.5) 59.6 ± 5.2 (49.3-70.0) 53.0 ± 14.7 (24.0-81.9) TILs 43.9 ± 4.6 (34.9-52.9) 35.0 ± 4.5 (26.2-43.7) 47.8 ± 5.7 (36.5-59.1) 35.0 ± 5.1 (24.9-45.0)
Table 3 Multivariate analysis including parameters associated with prognosis in the Log-rank test in the entire group and tumors of the intestinal subtype
Parameters All group P valueIntestinal tumors P valueHR Lower (95%CI) Upper (95%CI) HR Lower (95%CI) Upper (95%CI) ITB 2.06 1.40 3.01 < 0.001 3.32 2.34 4.72 < 0.001 PTB 1.83 1.29 2.59 < 0.001 2.01 1.32 3.05 < 0.001 LNM 1.53 1.00 2.33 0.04 1.09 0.59 2.04 0.760 Stage 1.06 0.81 1.40 0.63 1.12 0.80 1.58 0.480 Subtype 0.76 0.50 1.17 0.22 - - - - DR 1.11 0.87 1.42 0.39 1.17 0.86 1.60 0.290
Table 4 Tumor budding, desmoplastic reaction, and tumor-infiltrating lymphocytes in relation to clinicopathological parameters in the intestinal group
Parameters n PTB1 (%) PTB2 (%) PTB3 (%) ITB1 (%) ITB2 (%) ITB3 (%) DR1 (%) DR2 (%) DR3 (%) TILs (%) TILs (%) Age, yr 24 39 37 30 21 49 47 28 25 52 48 < 62.14 ± 12.00 47 10 (41.7) 24 (61.5) 13 (35.1) 14 (46.7) 11 (52.4) 22 (44.9) 21 (44.7) 15 (53.6) 11 (44.0) 25 (48.1) 22 (45.8) ≥ 62.14 ± 12.00 53 14 (58.3) 15 (38.5) 24 (63.9) 16 (53.3) 10 (47.6) 27 (55.1) 26 (55.3) 13 (46.4) 14 (56.0) 27 (51.9) 26 (54.2) Gender Male 60 15 (62.5) 24 (61.5) 21 (56.8) 18 (60.0) 15 (71.4) 27 (55.1) 34 (72.3) 16 (57.1) 10 (40.0)a 27 (51.9) 33 (68.8) Female 40 9 (37.5) 15 (38.5) 16 (43.2) 12 (40.0) 6 (28.6) 22 (44.9) 13 (27.7) 12 (42.9) 15 (60.0) 25 (48.1) 15 (31.3) Diameter < 1.86 ± 1.02 67 16 (66.7) 26 (66.7) 25 (67.6) 15 (50.0) 16 (76.2) 36 (73.5) 28 (59.6) 22 (78.6) 17 (68.0) 38 (73.1) 29 (60.4) ≥ 1.86 ± 1.02 33 8 (33.3) 13 (33.3) 12 (32.4) 15 (50.0) 5 (23.8) 13 (26.5) 19 (40.4) 6 (21.4) 8 (32.0) 14 (26.9) 19 (39.6) Invasion T1 7 5 (20.8) 2 (5.1) 0 4 (13.3) 1 (4.8) 2 (4.1) 3 (6.4) 3 (10.7) 1 (4.0) 4 (7.7) 3 (6.3) T2 28 4 (16.7) 15 (38.5) 9 (24.3) 12 (40.0) 7 (33.3) 9 (18.4) 14 (29.8) 9 (32.1) 5 (20.0) 12 (23.1) 16 (33.3) T3 42 10 (41.7) 13 (33.3) 19 (51.4) 9 (30.0) 6 (28.6) 27 (55.1) 23 (48.9) 12 (42.9) 7 (28.0) 23 (44.2) 19 (39.6) T4 23 5 (20.8) 9 (23.1) 9 (24.3) 5 (16.7) 7 (33.3) 11 (22.4) 7 (14.9) 4 (14.3) 12 (48.0) 13 (25.0) 10 (20.8) LNM Absent 69 22 (91.7) 29 (74.4) 18 (48.6)b 29 (96.7) 14 (66.7) 26 (53.1)b 39 (83.0) 19 (67.9) 11 (44.0)c 32 (61.5) 37 (77.1) Present 31 2 (8.3) 10 (25.6) 19 (51.4) 1 (3.3) 7 (33.3) 23 (46.9) 8 (17.0) 9 (32.1) 14 (56.0) 20 (38.5) 11 (22.9) Metastasis Absent 79 24 (100.0) 29 (74.4) 26 (70.3)d 21 (70.0) 20 (95.2) 38 (77.6) 39 (83.0) 23 (82.1) 17 (68.0) 40 (76.9) 39 (81.3) Present 21 0 10 (25.6) 11 (29.7) 9 (30.0) 1 (4.8) 11 (22.4) 8 (17.0) 5 (17.9) 8 (32.0) 12 (23.1) 9 (18.7) Stage I 20 11 (45.8) 9 (23.2) 0 10 (33.3) 5 (23.8) 5 (10.2)c 12 (25.5) 6 (21.4) 2 (8.0) 12 (23.1) 8 (16.7) II 26 6 (25.0) 10 (25.6) 10 (27.0) 7 (23.3) 4 (19.0) 15 (30.6) 15 (31.9) 9 (32.1) 2 (8.0) 12 (23.1) 14 (29.3) III 32 6 (25.0) 10 (25.6) 16 (43.2) 3 (10.0) 11 (52.4) 18 (36.7) 12 (25.5) 7 (25.0) 13 (52.0) 15 (28.8) 17 (35.2) IV 22 1 (4.2) 10 (25.6) 11 (29.7) 10 (33.4) 1 (4.8) 11 (22.4) 8 (17.0) 6 (21.4) 8 (32.0) 13 (25.0) 9 (18.8) Grade Low 54 19 (79.2) 21 (53.8) 14 (37.8)a 22 (73.3) 12 (57.1) 20 (40.8)a 28 (59.6) 16 (57.1) 10 (40.0) 29 (55.8) 25 (52.1) Moderate 29 2 (8.3) 13 (33.4) 14 (37.8) 3 (10.0) 6 (28.6) 20 (40.8 11 (23.4) 10 (35.7) 8 (32.0) 15 (28.8) 14 (29.2) High 17 3 (12.5) 5 (12.8) 9 (24.3) 5 (16.7) 3 (14.3) 9 (18.4) 8 (17.0) 2 (7.2) 7 (28.0) 8 (15.4) 9 (18.7) LVI Absent 67 13 (54.2) 26 (66.7) 28 (75.7) 15 (50.0) 15 (71.4) 37 (75.5) 34 (72.3) 14 (50.0) 19 (76.0) 32 (61.5) 35 (72.9) Present 33 11 (45.8) 13 (33.3) 9 (24.3) 15 (50.0) 6 (28.6) 12 (24.5) 13 (27.7) 14 (50.0) 6 (24.0) 20 (38.5) 13 (27.1) PNI Absent 71 14 (58.3) 26 (66.7) 31 (83.8) 18 (60.0) 15 (71.4) 38 (77.6) 34 (72.3) 16 (57.1) 21 (84.0) 37 (71.2) 34 (70.8) Present 29 10 (41.7) 13 (33.3) 6 (16.2) 12 (40.0) 6 (28.6) 11 (22.4) 13 (27.7) 12 (42.9) 4 (16.0) 15 (28.8) 14 (29.2) Survival Deceased 71 7 (29.2) 27 (69.2) 37 (100.0)b 7 (23.3) 16 (76.2) 48 (98.0)b 29 (61.7) 20 (71.4) 22 (88.0) 41 (78.8) 30 (62.5) Alive 29 17 (70.8) 12 (30.8) 0 23 (76.7) 5 (23.8) 1 (2.0) 18 (38.3) 8 (28.6) 3 (12.0) 11 (21.2) 18 (37.5) PTB PTB1 24 - - - 17 (56.7) 3 (14.3) 4 (8.2)b 14 (29.8) 8 (28.6) 2 (8.0)c 10 (19.2) 14 (29.2)d PTB2 39 - - - 13 (43.3) 18 (85.7) 8 (16.3) 23 (48.9) 11 (39.3) 5 (20.0) 16 (30.8) 23 (47.9) PTB3 37 - - - 0 0 37 (75.5) 10 (21.3) 9 (32.1) 18 (72.0) 26 (50.0) 11 (22.9) ITB ITB1 30 - - - - - - 21 (44.7) 8 (28.6) 1 (4.0)c 9 (17.3) 21 (43.8)c ITB2 21 - - - - - - 12 (25.5) 3 (10.7) 6 (24.0) 9 (17.3) 12 (25.0) ITB3 49 - - - - - - 14 (29.8) 17 (60.7) 18 (72.0) 34 (65.4) 15 (31.2) DR DR1 47 - - - - - - - - - 17 (32.7) 30 (62.5)d DR2 28 - - - - - - - - - 17 (32.7) 11 (22.9) DR3 25 - - - - - - - - - 18 (34.6) 7 (14.6)
Citation: Yavuz A, Simsek K, Alpsoy A, Altunay B, Gedik EO, Unal B, Bassorgun CI, Tatli AM, Elpek GO. Prognostic significance of tumor budding, desmoplastic reaction, and lymphocytic infiltration in patients with gastric adenocarcinoma. World J Gastrointest Pathophysiol 2024; 15(1): 91237
URL: https://www.wjgnet.com/2150-5330/full/v15/i1/91237.htm
DOI: https://dx.doi.org/10.4291/wjgp.v15.i1.91237