Comprehensive coverage of recent advances in Pancreatic cancer over the past decade

1. RECENT ADVANCES IN
PANCREATIC CANCER
Dr.E.Kaushik Kumar
Department of General Surgery
Stanley Medical College Hospital,Chennai

2. • Molecular Genetics and Tumour Biology
• Early Detection of Precursor Lesions
• Investigation Modalities
• Surgical Management
• Adjuvant modalities

3. Molecular Genetics and Tumour Biology
• Two eras

5. • Early Detection of Precursor Lesions
– PanIN
– IPMN
– Mucinous Cystic Neoplasm

6. Investigation Modalities
• TAUS
• EUS
• IOUS
• MD-CT
• MRCP
• Nuclear Imaging
• Tumour Markers

7. ULTRASOUND
• Screening
• 95.8% sensitive >3cm lesions
• Newer machines- Tissue Harmonic Imaging
• Colour Doppler
• IV Contrast imaging-100% specific for vascular
involvement
• PPV for unresectabilty-94%

8. EUS
• <3cm tumours,ampullary lesions
• Staging and resectability
• Reassessment after NAC
• EUS-FNA- 95% sensitivity,97% specificity,PPV
92%, 100% NPV
• Therapeutic options
– Intra-tumoral therapy(activated lymphocytic
cultures,viral vectors,oncolytic viruses)
– RFA/Cryotherapy
– Celiac plexus neurolysis

9. Homogenous echoes
Hypoechoic,irregular borders
Cyst- anecohic
Endocrine tumours-iso-echoic
Improper vascular involvement,
invasive,costly,operator dependent

10. Intra-operative US
• Depth of invasion
• Maximal longitudinal extent
• Vascular invasion
• Degree of resectability(20-35% will be
unresectable)
• Liver mets
• Localise islet cell tumours

12. MDCT
• Ill-defined, hypoattenuating focal mass with dilatation of
the upstream pancreatic and or biliary duct
• Arterial,Pancreatic and portal phases
• Very high spatial and temporal resolution
• Pancreatic Protocol-1 to 3 mm slice collimation
• challenging in the setting of
– pancreatitis forming mass effects
– in the presence of loco-regional lymph node
involvement
– small hepatic metastasis

13. • Vascular involvement include
– Tumor involvement for one half of the vessel′s
circumference
– Focal narrowing of the vessels
– Dilatation of peripancreatic veins.
• Perfusion imaging
– Angiogenesis in tumours
– Predict response to CCRT

14. MRI-MRCP
• High soft tissue contrast resolution
– Assessment of peripancreatic fat infiltration
– Evaluation of vascular encasement
– Peritoneal deposits and lymph nodal involvement
• MRS-differentiate CFP from pancreatic cancer
– proton MRS, CP shows less lipid than pancreatic
carcinoma due to difference in fibrous tissue content
in the two conditions

15. • Diffusion-weighted MRI differentiates the
subtypes of pancreatic endocrine
neoplasms
– Tumor cellularity
– Extracellular fibrosis
– Various apparent diffusion coefficient (ADC)
values in these tumors

16. MRI vs MDCT
Sensitivity Specificity
Anderson et al 92% v 76% 85% v 69%
Hanninen et al 97% 81%
Park et el (GE-MRI) 83-85% v 83% 63% v 63-75%
Grenacher et el 82-94% v 100%
Bigat et al 84% v 91%

17. Nuclear Imaging
• Newly developed PET scanners can
detect small PCs up to 7 mm in diameter
• Unsuspected Bone metastasis(40%)
• Inflammatory pathology
• Tumour viability
• Response to treatment

18. Optical coherence tomography
• Infrared light to produce high-resolution, cross-sectional,
subsurface imaging of the microstructure.
• Recognize different patterns of
the duct wall structure in
neoplastic and non-neoplastic
conditions
• High diagnostic accuracy,
better than brush cytology

20. Tumour Markers
Marker Sensitivity Specificity
CEA 45% 75%
CA 19-9 80% 43%
CA 242 60% 76%
CEA + CA 19-9 37% 84%
CEA + CA 242 34% 92%

21. • CA494
• CEACAM1
• PTHrP
• TuM2-PK
• CAM 17.1
• Serum beta HCG

22. Surgical Management
• Resectability criteria
– Resectable
– Borderline Resectable
– Unresectable

23. • Laparoscopy
– Staging
– Therapeutic
– Safe and Better outcome

24. • Robotic Surgery
– 3-Dimensional
– Dexterity
– Ergonomics

25. Adjuvant modalities
• FOLFIRINOX(5-fluorouracil, leucovorin, irinotecan,
oxaliplatin)
– ACCORD trial -median overall (11.1 mo vs 6.8 mo)
– Grade 3-4 toxicities
• Gemcitabine + nab-Paclitaxel (MPACT)
– Improved median overall survival (8.5mo vs 6.7 mo)
– Improved 1-year survival (35% vs 22%)
– Improved 2-year survival (9% vs 4%)
– Improved objective response rate

26. • Gemcitabine plus erlotinib
– improved progression-free survival and
overall survival
– hNET1 expression  Gemcitabine response

28. S-1
• An oral 5-fluorouracil (5-FU) prodrug
– Tegafur (a prodrug of 5-FU)
– Gimeracil [a potent dihydropyrimidine dehydrogenase
(DPD) inhibitor]
– Oteracil(an inhibitor of phosphorylation of 5-FU in GIT)
• First-line Chemotherapy for Metastatic/Locally Advanced
Pancreatic Cancer
• Second-line Therapy After Gemcitabine Failure
• CRT For Locally Advanced Pancreatic Cancer
• Adjuvant Chemotherapy For Resected Pancreatic Cancer
• Improved ORR

29. • Neo-Adjuvant ChemoRadiotherapy
– Chemotherapy provides control for a micro-
disseminated disease & also acts as a
radiation sensitizer
– Radiotherapy(RT) may have a huge impact
on the local control of the disease.

31. • Upfront chemotherapy followed by CRT
– Early therapeutic approach may use not only
RT-sensitizing drugs and drugs that are more
effective against cancer such as 5-FU and
Gemcitabine or Capecitabine
– Select patient who did not progress, thus
avoiding the additional toxicity of unnecessary
Radiotherapy (RT)
• End point – Resectability as per NCCN

33. • IORT
– When followed after pre-operative
chemotherapy and surgery gives a 5-yr local
control of 23.3%

35. Multidisciplinary

36. • Mortality and morbidity directly proportional to
Institutional Volume of cases
• “A persistent nihilism of clinicians towards PC
and pancreatectomy may be the most significant
correctable factor that contributes to the current
poor long-term outcomes of PC.”
• Birkmeyer et al,Bilimoria et al

37. • What have we understood?
• What has improved?
• Where do we stand?
• What needs to be done?

39. References
• Blumgart textbook of HPB Diseases,5th
edition
• World Journal of Gastroenterology(2001-2014)
– Pancreatic cancer: Advances in treatment
– Recent advances in the surgical treatment of pancreatic cancer
– Selection criteria in resectable pancreatic cancer: A biological and
morphological approach
– Imaging diagnosis of pancreatic cancer: A state-of-the-art review
– Diagnostic Imaging for Pancreatic Cancer Computed Tomography,
Magnetic Resonance Imaging, and Positron Emission Tomography
– Advances in diagnosis, treatment and palliation of pancreatic
carcinoma: 1990-2010
– S-1 in the treatment of pancreatic cancer Kentaro Sudo, Kazuyoshi
Nakamura, Taketo Yamaguchi
– Recent standardization of treatment strategy for pancreatic
neuroendocrine tumors Masayuki Imamura
– Neoadjuvant strategies for pancreatic cancer

40. Thank You 