Recurrence Patterns of Curative Resected Ampulla of Vater Cancer : Significance of Lymph Node Dissection Around Superior Mesentery Artery Hongbeom Kim, Jae Ri Kim, Wooil Kwon, Jin-Young Jang, Sun-Whe Kim Division of Hepatobiliarypancreas Surgery Department of Surgery Seoul National University College of Medicine

Background Ampulla of Vater (AoV) cancer have better prognosis than other peri-ampullary cancers. Prognosis of AoV cancer : different according to the stage → necessary to establish treatment guideline according to the stage AoV cancer Overall survival rate Distal CBD cancer Duodenal cancer Pancreas head cancer 1983-2012 SNUH data Unpublished Month 이 슬라이드에서는 첫번째 문장과 생존그래프가 불필요하고 아래 내용만 있으면 될것 같다는 말씀이셨는데, 전보다 여백이 많이 생긴 것 같고 아래 것으로 한 페이지 채우려면 너무 썰렁하니 그냥 두는 것도 괜찮겠다. 너가 정해라. Treatment strategy must be based on tumor biology and recurrence pattern

Purpose To figure out recurrence patterns according to the stage in AoV cancer To suggest optimal treatment of AoV cancer To identify significance of SMA node dissection based on recurrence pattern in AoV cancer 이 페이지에서는 ca 말고 cancer 다 쓰라는 말씀으로 기억됨.

Methods Jan. 2000 ~ Jun. 2012, 259 AoV cancer patients with R0 resection by Pancreaticoduondenectomy Extent of LN dissection around SMA and celiac axis: up to Rt. side of SMA and celiac axis Recurrence pattern and risk factors analysis Recurrence sites identification: CT / MRI / PET 사진 바꾸기

Demographics Variables N=259 Age* (yr) 61.7 ± 10.1 Sex, M:F 138 : 121 Operation Whipple’s op PPPD TP** 52 204 3 (20.1%) (78.8%) (1.2%) Histology W/D M/D P/D 84 154 21 (32.4%) (59.5%) (8.1%) Adjuvant Tx. 122 (47.1%) Variables N=259 Stage Ia Ib IIa IIb III 71 58 57 74 2 (27.4%) (22.4%) (20.8%) (28.6%) (0.8%) T classification T1 T2 T3 T4 80 81 96 (30.9%) (31.3%) (37.1%) LN metastasis 76 (29.3%) *Mean ± SD **Total pancreatectomy

Survival and recurrence rate Median F/U period : 40.7 months Recurrence: 89 case (34.4%) Median recur time: 15.3m Recurrence free survival rate: 62.1% Overall survival rate: 56.1% Local only Local + Distant Distant only 19 (21.3%) 14 (15.7%) 56 (62.9%)

Risk factors of recurrence Univariate analysis Multivariate analysis No Recur n=170 Recur n=89 P value Hazard Ratio 95% CI P value Sex M 89 (52.4%) 49 (55.1%) 0.679 F 81 (47.6%) 40 (44.9%) Age* (year) 61.1 ± 10.1 62.8 ± 10.0 0.185 Histology W/D 73 (42.9%) 11 (12.4%) <0.001 .002 M/D 90 (52.9%) 64 (71.9%) 3.061 1.436 – 6.527 .004 P/D 7 (4.1%) 14 (15.7%) 6.914 2.121 – 22.541 T T1 68 (40.0%) 12 (13.5%) .010 T2 55 (32.4%) 26 (29.2%) 1.619 0.709 – 3.699 .253 T3/4 47 (27.6%) 51 (57.3%) 3.192 1.439 – 7.081 N N0 138 (81.2%) 45 (50.6%) N1 32 (18.8%) 44 (49.4%) 2.578 1.394 – 4.767 Multivariate에서는 95% CI 어지간하면 써주자. 그리고 %는 행 중 % 말고 열 중 % 를 적어야 할 것 같은데.. 예를 들면 No recur group에서 남자가 89명으로 52.4%고 여자가 51명으로 47.6%. 그 그룹의 전체에서 차지하는 비율에 차이가 있음을 검정하는 것이므로… 그리고 multivariate에서 N1이 HR 2.309인거 맞지?? *Mean ± SD

Recurrence at 149 sites in 89 patients Recurrence site Recurrence at 149 sites in 89 patients Locoregional recur. N = 33 n LN SMA 21 CHA 5 Porto-caval 2 Celiac 1 PJ Pancreas HJ Distant recur. N = 116 n Liver 52 Lung 18 Peritoneal seeding 15 Distant LN 23 Bone 4 Adrenal 2 Brain

Factors associated with recurrence patterns Variable N=89 Local only n=19 Local + distant n=14 Distant only n=56 P value Sex M 7 (36.8%) 9 (64.3%) 33 (58.9%) 0.186 F 12 (63.2%) 5 (35.7%) 23 (41.1%) Age* (year) 66.1 ± 6.9 59.6 ± 9.5 62.5 ± 10.8 0.174 Histology W/D (26.3%) 2 (14.3%) 4 (7.1%) 0.192 M/D 11 (78.6%) 41 (73.2%) P/D (10.5%) 1 (19.6%) T T1 (58.3%) 3 (25.0%) (16.7%) 0.003 T2 6 (23.1%) (11.5%) 17 (65.4%) T3/4 (11.8%) 8 (15.7%) 37 (72.5%) N N0 14 (73.7%) 22 (39.3%) 0.019 N1 34 (60.7%) Adjuvant Tx. No 10 (52.6%) 16 (28.6%) 0.163 Yes (47.4%) 40 (71.4%) 이전과 마찬가지로 %를 각 그룹에 대한 것으로 바꿔줘.. 통계량은 차이 없을 것이야… *Mean ± SD

Sites of locoregional and LN recurrence Celiac Portocaval CHA PJ stomy T1 T2 T3 HJ Pancreas, tail N0 N1 DJ stomy Aortocaval space Lt. para-arotic area Along the SMA Rt. Mid Lt. 3 15

SMA recur. according to the T stage 아마도 T stage가 높아짐에 따라 non-SMA recur의 빈도가 증가한다는 이야기를 하려고 사용한 통계 같은데, 그렇다면 %를 다르게 써야 할 것 같다. 그리고 Total recur 열은 없어도 될 듯 SMA recur (+) n=21 non-SMA recur n=68 p-value T1 7 (58.3%) 5 (41.7%) 0.007 T2 6 (23.1%) 20 (76.9%) T3/4 8 (15.7%) 43 (84.3%)

Effect of adjuvant therapy, chemo Tx. T2,3,4 N=178 Chemo Tx. (+) (n=78) Chemo Tx. (+) (n=78) Chemo Tx. (-) (n=100) Chemo Tx. (-) (n=100) P=0.072 P=0.240 Month Month Recurrence free survival rate Overall survival rate

Effect of adjuvant therapy, Radio Tx. LN meta. (+) N=76 Radio Tx. (+) (n=52) Radio Tx. (+) (n=52) Radio Tx. (-) (n=24) P=0.005 Radio Tx. (-) (n=24) P=0.007 Month Month Local recurrence free survival rate Overall survival rate

Summary 5-YSR of curative AoV cancer. : 56.1% Recurrence rate: 34.4% (local: 21.1%, distant: 78.8%) Risk factor of recurrence Higher T classification LN metastasis Differentiation (worse differentiation) Most common recurrence site : Liver Most common LN recurrence site : SMA LN (8.1%) Current chemotherapy has limited impact on outcome → Better chemotherapy agent or regimen needs to be uncovered Radiotherapy improves DFS and OS in LN (+) patients Distant recurrence rate가 어떻게 68.8%인지? 70/259가 맞을 것이고 recur 중 distant meta를 알고 싶다면 70/89 아닌가 모르겠다.

Conclusion Recurrence pattern is different according to the T stage Early stage Advanced stage Local recurrence, esp. SMA area Systemic recurrence Elaborate LN dissection around SMA region is important Aggressive adjuvant treatment should be exerted postoperatively

Thank you !