1. IN THE NAME OF GOD

2. Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy The American Journal Of Surgery By: Z.Jokar

3. Pancratic ductal adenocarcinoma (PDA) One of the most deadly malignancies Surgical resection is necessary Surgery : locally advanced 20% borderline 50%

4. Compare between : Neoadjuvant Upfront resection

5. Jun. 2001 – Dec. 2008 LOCALLY ADVANCED UNRESECTABLE 41 (10.1%) BORDERLINE RESECTABLE 403 362 (89.9%) UPFRONT RESECTION

6. Staging Abdominal U.S. Multi detector CT (contrast)/ MRI Endoscopic U.S. CA 19-9 Pathological confirm

7.  Locally advance unresectable: Tumor involvement > 180 Thrombosis of the portomesentric venous system  Borderline resection: Tumor involvement < 180 Short segment encasement/occlusion of the smv or portal vein amenable to vascular resection and reconstruction

8. Treatment sequencing & evaluation External-beam radiotherapy Chemotherapy (gemcitabine)

9. Therapeutic response CT ( 4-6 weeks after end of treatment ) Response evaluation criteria in solid tumors

10. Pathologic examinations &responses < 0.05 LNR 0.05 – 0.2 > 0.2 I :COMPLETE-ALMOST COMPLETE REGRESSION/ VIABLE TUMOR CELLS <10% Grade II :PARTIAL REGRESSION /VIABLE TUMOR CELLS 10-90% III :NO-MINIMAL REGRESSION /VIABLE TUMOR CELLS 10-90%

11. Statistical analysis Median number IQR

12. Results Neoadjuvant: 27(66%) : borderline 41 patients (59 y /21 malel/ 20 female) 14(44%) : locally advanced 10 patients (42%) previous surgical palliation 17 (41.5%) : only chemotherapy 24 (58.5%) : chemoradiotherapy

13. Ca 19-9 : 246.5 u/ml 93 u/ml Neoadjuvant group had a higher median value of ca 19-9 at diagnosis Median radiologic tumor size : 35 mm 20 mm

14. Surgical treatment No statistically differences The median length of stay of the neoadjuvant group was significantly longer (14 vs 10 d) Post operative bleedingReoperation Upfront resection4.1%3.7% neoadjuvant9.8%13.3%

15. Adjuvant therapy after surgery Neoadjuvant : 32(78%) Upfront resection : 291(82%)

16. Pathology Grade I : 3(7%) Neoadjuvant Grade II : 14(34%) Grade III : 24(59%)

17. The medictionan number of evaluated nodes was significantly higher for the upfront group (23 vs 15) Neoadjuvant: 70.7% R0 resection Upfront: 59.7% R0/R1/R2 Did not differ R0 margins 35% chemotherapy alone R0 margins 96% chemoradiotherapy

18. Survival In upfront group 16(4.4%) were lost to followup The median survival time did not differ : Neoadjuvant : 35 m Upfront : 37 m

19. Prognostic factors Poor survival : R2 resection G3/G4 tumors LNR > 0.2 Body/tail tumors No adjuvant treathment Only chemoradiation as neoadjuvant treatment was an independent predictor of survival

20. Comments 10 patients (42%) previous surgical palliation 76% based on high resolution imaging

21. Preoperative complications were more in neoadjuvant group (systemic complications/hemorrhage/reoperation) The median surgical time No difference The rate of post operative mortality/morbidity Specific complications Only the median postoperative length of stay was significantly linger in the neoadjuvant group (14 vs 10d)

22. Grade I : 3(7%) Neoadjuvant Grade II : 14(34%) Grade III : 24(59%) Grade I : 12% Chemoradiation Grade II :2% Grade III :42% Grade I : 0% Chemotherapy Grade II :17% Grade III :82%

23. Median radiologic tumor size : 35 mm 20 mm Neoadjuvant :15 The median number of L.N Upfront :23 Nodal downstaging in neoadjuvant group

24. R0 margins 35% chemotherapy alone R0 margins 96% chemoradiotherapy The median survival time did not differ : neoadjuvant : 35 m Upfront : 37 m Only chemoradiation as neoadjuvant treatment was an independent predictor of survival

25. Conclusion Surgical resection after downstaging of locally advanced and borderline resectable pancreatic cancer should be offered to all surgically fit patients without an increased post operative mortality/morbidity Patients resected after neoadjuvant treatment have at least the same survival rate of patients with resectable disease who undergo primary resection

26. THANK YOU FOR YOUR ATTENTION