Introduction Classification Risk Factors Manifestations Role of Tumor markers Imaging Management www.GambatLivertransplant.com

2. DR. ABDUL GHAFFAR
PANCREATIC CANCER
PRESENTED BY

3. CONTENT
• Introduction
• Classification
• Risk Factors
• Manifestations
• Role of Tumor markers
• Imaging
• Management

4. INTRODUCTION
 Pancreatic cancer is the second MC GI malignancy.
 Pancreatic cancer ranks 10th in cancer incidence in the US for men and women.
 The fourth most fatal cancer in men after lung, colorectal, and prostate
cancers .
 Similarly, PC was found to be the fourth most fatal cancer in women after breast,
colorectal and lung cancer.

5. WHO CLASSIFICATION OF PRIMARY
TUMORS OF THE EXOCRINE PANCREAS
s

7. CHARACTERISTICS OF VARIOUS ETP

8. DUCTAL ADENOCARCINOMA OF
PANCREAS
• Ductal adenocarcinoma accounts for 85% to 90% of pancreatic
tumors.
• Autopsy series have shown that 60%-70% of these tumors are
localized in the head of the gland, 5%-10% in the body, and 10%-
15% in the tail.
• The average size of carcinomas in the head of the pancreas is 2.5 to
3.5 cm, compared with 5 to 7 cm for tumors in the body or tail.

10. MANIFESTATIONS
• Tumors of the head of the pancreas produce symptoms earlier in
the course of disease.
• Tumors in the head of the gland have a propensity for obstruction
of the distal CBD and pancreatic duct.
• Anatomic obstruction of these structures results in jaundice and
chronic obstructive pancreatitis.
• Some tumors can involve the duodenum or the ampulla of Vater.
• Extrapancreatic extension into the retroperitoneal tissues is almost
always present at the time of DX and can result in invasion of the PV
or the superior mesenteric vessels and nerves.

11. MANIFESTATIONS
• In contrast, tumors of the distal gland are characterized by their “silent”
presentation
• Neoplasms of the tail of the pancreas do not cause biliary or pancreatic
duct obstruction.
• Extrapancreatic extension in distal tumors causes invasion of the spleen,
stomach, splenic flexure of the colon, or left adrenal gland.
• In pts with advanced disease, metastases to the lymph nodes, liver, and
peritoneum are common.

12. MANIFESTATIONS: MAJOR
• Jaundice is often the first sign that brings pts to medical attention,
especially with tumors in the head of the pancreas.
• Pts with concomitant obstruction of the pancreatic duct may also
show pancreatic exocrine insufficiency in the form of steatorrhea and
malabsorption.
• Pain can be a major symptom in many pts with PC. The pain also
may be postprandial and lead pts to reduce their caloric intake, a
situation that ultimately results in weight loss or cachexia.

13. MANIFESTATIONS
• In a multi-institutional series of 185 pts with exocrine PC DX over a 3-yr period (62
% involving the head, 10 % body, 6 % tail, and the remainder not determined).
Symptoms Signs

14. ROLE OF TUMOR MARKERS
CA 19-9- SN and SP rates for PC range from 70-92, and 68-92%,
respectively.
However, SN is closely related to tumor size. CA 19-9 levels are of limited
SN for small cancers.
 One study found that serum conc > 37 U/mL represented the most
accurate cutoff value for discriminating PC from benign pancreatic disease.
 CA 19-9 >130 units/mL were a significant predictor of radiographically
occult unresectable disease .

15. CONDITIONS WITH INCREASED
SERUM LEVELS OF CA 19-9

16. IMAGING OF PANCREATIC CANCER
Although transabdominal US is frequently the first modality used in
many pts with PC(because 50% of them present with jaundice), the
method of choice for DX and staging of PC is CT.
The SN of detecting PC on CT scan varies from 67% to 100%
depending on the size of the primary lesion.

17. DIAGNOSIS: CT
The pancreatic protocol CT consists of dual-phase scanning using IV
contrast agents.
The first, arterial (pancreatic) phase is obtained 40 secs after
administration of IV contrast agent. At this time maximum enhancement of
the normal pancreas is obtained, allowing identification of nonenhancing
neoplastic lesions.
The second, portal venous phase(Hepatic phase) is obtained 70 secs
after injection of IV contrast agent and allows accurate detection of liver
metastases and assessment of tumor involvement of the portal and
mesenteric veins.

18. CT SCAN OF PC
A, Arterial phase showing a nonenhancing lesion in the head of the pancreas (arrows).
B, Venous phase showing a noninvolved fat plane around the portal vein (arrows).

19. ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY

20. ENDOSCOPIC ULTRASONOGRAPHY
EUS may be the most accurate test for the DX of PC.
EUS also has been found to be more accurate than CT in assessing
vascular invasion and predicting tumor resectability.
Other advantages of EUS include accurate assessment of peripancreatic
nodal disease, and allowance of tumor biopsy by FNA.

21. EUS OF PC: LIMITATIONS
EUS is highly operator-dependent, and it is estimated
that experience with 100 such examinations is needed to
be considered proficient.[1]
Imaging by EUS can be compromised by the presence
of a biliary stent, which results in imaging artifacts and
loss of tissue detail.
Due to technical and anatomic constraints, imaging of the
PV and splenic vein is generally superior to imaging of the
superior mesenteric artery and vein.[2] For this reason EUS
may lack accuracy when assessing vascular invasion
at the level of the superior mesenteric vessels.
Lastly, EUS provides no information regarding
metastatic disease, and a complementary CT or MRI
scan is required for complete staging of disease.
This EUS image demonstrates PC invasion of the PV (outlined area).

22. MAGNETIC RESONANCE IMAGING
• MRI has been increasingly used in the evaluation of pancreatic tumors, and
several groups have shown results that rival those of helical CT.
• In one study, pancreatic tumor detection was reported in 90% of pts for
MRI versus 76% for helical CT.
• Tumors are viewed as low-signal masses against the high-signal
background of normal pancreatic parenchyma.
• Pancreatic masses, ductal dilation, and liver metastasis can be
demonstrated in exquisite detail.
• Additionally, MR angiography and MR venography techniques using
gadolinium contrast enhancement can demonstrate vascular involvement
by tumor.
• Unlike CT, MRI does not involve radiation and uses an iodine-free
contrast agent with rare renal toxicity.

23. POSITRON EMISSION TOMOGRAPHY
PET is a noninvasive imaging tool that provides metabolic rather
than morphologic information
The normal pancreas is not usually visualized by FDG-PET. In
contrast, PC appears as a focal area of increased uptake in the
pancreatic bed.
Hepatic metastases appear as “hot spots” within the liver.

24. TNM SYSTEM / AMERICAN JOINT COMMITTEE
ON CANCER (AJCC)
STAGING OF PANCREATIC CANCER

25. STAGING
• The system was last revised in 2002, and modifications were made to better
identify unresectable (T4, stages III and IV) from resectable disease (T1-3,
stages I and II).
• Several limitations of the staging system exist.
1. Adequate evaluation of lymph node status cannot be performed
without surgical intervention; this drawback may lead to understaging of
locally advanced disease in pts who are not candidates for laparotomy.
2. The margins of resection, which carry great prognostic significance, are
not taken into consideration when assigning clinical stage.
• Because of these and other shortcomings, the AJCC staging system has
found limited clinical applicability.

26. DEFINITION OF RESECTABILITY
ACCORDING TO NCCN GUIDELINES
Resectability
status
Arterial Venous
Resectable No arterial-tumour contact [coeliac axis (CA), SMA, or
CHA]
No tumour contact with the SMV, or PV
or <180° contact without vein contour
irregularity
Borderline
Resectable
Pancreatic
head/uncinate
process
• Solid tumour with CHA without extension to coeliac
axis or hepatic artery bifurcation allowing for safe
and complete resection and reconstruction • Solid
tumour contact with the SMA <180°
• Presence of variant arterial anatomy (e.g.
accessory right hepatic artery) and the presence
and degree of tumour contact should be noted if
present as it may affect surgical planning
• Solid tumour contact with the SMV or
PV of >180°, contact of <180° with
contour irregularity of the vein or
thrombosis of the vein but with suitable
vessels proximal and distal to the site
of involvement allowing for safe and
complete resection and vein
reconstruction
• Solid tumour contact with IVC
Borderline
Resectable
Pancreatic
body/tail
• Solid tumour contact with the CA of <180°
• Solid tumour contact with the CA of >180° without
involvement of the aorta and with intact and
uninvolved gastroduodenal artery (some members
prefer these criteria to be in the unresectable
category)

27. DEFINITION OF RESECTABILITY
ACCORDING TO NCCN GUIDELINES
Resectability
status
Arterial Venous
Unresectable • Distant metastases
Pancreatic head/uncinate process
• Solid tumour contact with SMA >180°
• Solid tumour contact with the CA >180°
• Solid tumour contact with the first jejunal
SMA branch
Body and tail
 Solid tumour contact with the SMA and
CA
 Solid tumour contact with the CA and
aorta
Pancreatic head/uncinate process
• Unreconstructible SMV/PV due to
tumour involvement or occlusion (can be
due to tumour or bland thrombus)
• Contact with most proximal draining
jejunal branch into SMV Body and tail
• Unreconstructible SMV/PV due to
tumour involvement or occlusion (can be
due to tumour or bland thrombus)

28. MASSACHUSETTS GEN HOSPITAL ALGORITHM
FOR DX AND STAGING OF PC

29. MANAGEMENT

30. TREATMENT: SURGICAL THERAPY
• Surgical resection is the only potentially curative RX for PC.
Because of advanced disease at presentation, only about 15% to
20% of pts are candidates for pancreatectomy.
• The main goal of surgery is to achieve negative (R0) resection
margins.

31. TREATMENT: SURGICAL THERAPY
• The MC operation for PC is the Whipple
pancreaticoduodenectomy, which removes primarily the head of
the pancreas.
• However, total pancreatectomy has not been shown to improve
survival when compared with the more limited
pancreaticoduodenectomy, and results in exocrine insufficiency
and brittle DM, which are difficult to manage.
• Other extensions to the standard Whipple procedure, such as
addition of retroperitoneal lymphadenectomy, have shown no
significant survival benefit and may result in additional morbidity
(longer hospital stays, increased rates of pancreatic fistula, and
higher incidence of delayed gastric emptying).

32. DIAGRAM OF THE PYLORUS-PRESERVING
PANCREATICODUODENECTOMY

33. TREATMENT: SURGICAL THERAPY
• In the past, PD was a/with high morbidity and mortality rates. Many
contemporary large series now consistently show mortality rates
of <3%, with a concomitant decrease in complications.
• Pancreatic fistula, the MC and dreaded complication after the
Whipple procedure, is observed in only 5% to 10% of pts today.
These changes have been attributed to the emergence of ICU, as
well as advances in surgical technique, anesthesia, antibiotics, and
interventional radiology.

34. TREATMENT: SURGICAL THERAPY
• Ultimately, prognosis for PC remains poor, even after potentially
curative SX in appropriately selected pts.
• Five-year actuarial survival rates range from 10.5% to 25% and
median survivals between 10.5 and 20 months.
Significant predictors of a better outcome
• Tumor size <3 cm
• Absence of lymph node metastases
• Negative resection margins
• Well-differentiated tumors
• Intraoperative blood loss of <750 mL.

35. PREOPERATIVE BILIARY DRAINAGE ?
• A recent prospective and randomised trial demonstrated an increased
complication rate a/with routine preoperative biliary drainage.
• However, pts in the trial had a total bilirubin level below 14 mg/dL.
Therefore, the correct approach in pts with higher levels remains
undefined.
• If jaundice is present at DX of PC, endoscopic drainage should only be
carried out preoperatively
• In pts with active cholangitis
• In those whom resection for cure cannot be scheduled within 2 weeks of DX
• In those with a bilirubin level above14 mg/dL.

36. RECOMMENDATIONS FOR RX OF
LOCALISED DISEASE
• A multidisciplinary team is necessary.
• Tumour clearance should be given for all seven margins identified by
the surgeon .
• Standard lymphadenectomy should involve the removal of ≥15
lymph nodes to allow adequate pathologic staging of the disease .
• Adjuvant treatment is done with either gemcitabine or 5-FU folinic
acid.
• No chemoradiation should be given to pts after SX except in
clinical trials.

37. MANAGEMENT

38. BORDERLINE RESECTABLE LESIONS
Tumours are considered resectable upon good response to
neoadjuvant RX. Including,
a period of chemotherapy followed by chemoradiation
and then surgery appears to be the best option.

39. MANAGEMENT

40. LOCALLY ADVANCED DISEASE
When the pt has no metastases and the tumour is not considered as
borderline resectable, the tumour is defined as truly locally advanced .
Treatment of this group of pts remains highly controversial. However, in
the recent LAP07 trial , which included only pts with locally advanced
disease the overall median survival of the pts RX with chemotherapy
alone was 16 months.
The standard of care is 6 months of gemcitabine .
A minor role of chemoradiation in this subgroup of pts has
been observed( classical combination of capecitabine and
radiotherapy).

41. MANAGEMENT

42. TREATMENT OF
ADVANCED/METASTATIC DISEASE
Palliative and supportive care
• Before even considering systemic chemotherapy, pts with metastatic
PC may need interventions to provide relief of biliary and/or
duodenal obstruction, malnutrition, and pain.

43. PHASE III ADJUVANT TRIALS IN
PANCREATIC CANCER

44. PALLIATIVE PROCEDURES: JAUNDICE
• Relief of jaundice can also be achieved by biliary stents placed percutaneously or
endoscopically. Because these procedures are usually well tolerated and perfomed
on an outpatient basis.
In the event of a biliary obstruction due to a pancreatic tumour, the endoscopic
placement of a metallic biliary stent is strongly recommended. The endoscopic
method is safer than percutaneous insertion and is as successful as surgical
hepatojejunostomy.
Duodenal obstruction is preferentially managed by endoscopic placement of an
expandable metal stent when possible, and is favoured over surgery`

45. PALLIATIVE PROCEDURES: PAIN
Pain in PC can be extremely distressing and may respond poorly to
oral narcotics.
EUS/Percutaneous/ or surgical chemical neurolysis with alcohol
is an alternative palliative measure that can help in controlling pain or
decreasing narcotic use.
Randomized trials have shown that neurolysis of the celiac
ganglion can offer relief to many pts.s
Lastly, radiation therapy may also be used for pain MX in selected
pts.

46. MANAGEMENT ALGORITHM

47. CANCER CACHEXIA
• Cancer cachexia is a universal feature of advanced PC. The
majority of weight loss is secondary to the still poorly understood
paraneoplastic effects of the tumor on metabolism and calorie
utilization.
• Agents targeting various cytokines such as interleukin-1α (IL-1α),
thought to contribute to cachexia are now being evaluated.
• For PC pts, pancreatic enzyme supplementation should be
provided .
• Oral administration of exogenous pancreatic enzymes is
considered standard therapy.

48. CYSTIC NEOPLASM OF PANCREAS

49. PRESENTATION

50. CHARACTERISTICS