This document provides information on pancreatic adenocarcinoma, including its anatomy, physiology, clinical presentation, investigations, staging, treatment and prognosis. It discusses the exocrine and endocrine functions of the pancreas. It also covers cystic lesions of the pancreas and pancreatic endocrine tumours. The staging and survival rates for pancreatic cancer are presented. Complications of pancreatic surgery and mortality rates at high volume centers are summarized.
6. Physiology – Exocrine Pancreas
• Secretion of water and electrolytes originates in the
centroacinar and intercalated duct cells
• Pancreatic enzymes originate in the acinar cells
• Final product is a colourless, odourless, and
isosmotic alkaline fluid that contains digestive
enzymes (amylase, lipase, and trypsinogen)
7. Physiology – Exocrine Pancreas
• Alkaline pH results from secreted bicarbonate
which serves to neutralize gastric acid and regulate
the pH of the intestine
• Enzymes digest carbohydrates, proteins, and fats
8. Enzymes
• Amylase
– only digestive enzyme secreted by the pancreas in an active form
– functions optimally at a pH of 7
– hydrolyzes starch and glycogen to glucose, maltose, maltotriose,
and dextrins
• Lipase
– function optimally at a pH of 7 to 9
– emulsify and hydrolyze fat in the presence of bile salts
9. Endocrine Function: Insulin
• Synthesized in the B cells of the islets of Langerhans
• 80% of the islet cell mass must be surgically removed
before diabetes becomes clinically apparent
• Proinsulin, is transported from the endoplasmic
reticulum to the Golgi complex where it is packaged into
granules and cleaved into insulin and a residual
connecting peptide, or C peptide
11. Glucagon
• Secreted by the A cells of the islet
• Glucagon elevates blood glucose levels through the
stimulation of glycogenolysis and gluconeogenesis
• Major stimulants
– Aminoacids, Cholinergic fibers, β-Sympathetic fibers
• Major inhibitors
– Glucose, insulin, somatostatin, α-sympathetic fibers
12. Somatostatin
• Secreted by the D cells of the islet
• Inhibits the release of growth hormone
• Inhibits the release of almost all peptide hormones
• Inhibits gastric, pancreatic, and biliary secretion
• Used to treat both endocrine and exocrine disorders
14. Pancreatic cancer
• Fourth leading cause of cancer-related death
• > 7000 deaths annually in UK
• Overall 5-year survival approx 1%
• Only approx 13% alive after 1 year
• Often called the “silent disease” because it usually
doesn’t cause symptoms in early stages
15. • M > F (2:1) and 2% of all tumours
• Association with smoking, hypertension, obesity
• Presents in 5th decade
• Risk factors:
– Tuberous sclerosis
– Von Hippel-Lindau disease (clear cell)
– Renal transplantation
– Dialysis
Some interesting facts
16. Aetiology
• Cause unknown
• Smoking & alcohol?
• Diabetes? (5 years greater than 2x increase)
• Hereditary pancreatic cancer – susceptibility locus has been found in relation to
chromosome 4q32-34
• Familial breast cancer gene (BRCA2)
• Chronic pancreatitis
19. Mortality
0
10
20
30
40
50
one-year five-year one-year five-year
%survival
1971-1975
1976-1980
1981-1985
1986-1990
1991-1995
1996-1999
1998-2001*
* England only
Figure 3.1: One- and five-year relative survival by sex, adults
diagnosed with pancreatic cancer, England and Wales, 1971-
2001 and followed up to the end of 2003
Males Females
20. • Renal mass
• Haematuria
• Flank pain
– Complete triad = poor prognosis
• Remember pts often asymptomatic
– Malaise, weight loss, polycythaemia, hypertension can
also be seen.
Clinical presentation (triad)
21. Clinical presentation
• Weight loss
• Anorexia
• Nausea & vomiting
• Abdominal pain
• Obstructive jaundice (head lesions)
• Cachexia
• Very difficult to diagnose in early stage
22. Investigations
Radiological
• CT – identify renal lesion +
involvement of renal vein or IVC
• USS – tell if mass is cystic or
solid, and if TCC or RCC
• MRI & MRCP – good for staging
• ERCP
• Endoscopic USS
• Intravenous urogram (IVU)
• CT-PET
Bloods
• ESR usually raised
• LFTs may be abnormal
• FBC
• U&E’s
• Tumour marker: CA 19-9
Laparoscopy
25. ERCP
+ Accuracy of 60%-80 % by imaging alone.
- 5%-10% complication rate.
Tissue/Brushings
+ Diagnostic yield in the range of 40% to 50%.
- Up to 11% and 21% complication rate
Double duct
sign
Distal CBD stricture
37. Staging: TMN
T categories
• TX: The main tumour cannot be assessed.
• T0: No evidence of a primary tumour.
• Tis: Carcinoma in situ (very few tumours are
found at this stage)
• T1: The cancer has not spread beyond the
pancreas and is smaller than 2 cm (about ¾ inch)
across.
• T2: The cancer has not spread beyond the
pancreas but is larger than 2 cm across.
• T3: The cancer has spread from the pancreas to
surrounding tissues near the pancreas but not to
major blood vessels or nerves.
• T4: The cancer has extended further beyond the
pancreas into nearby large blood vessels or
nerves.
N categories
• NX: Regional lymph nodes cannot be assessed.
• N0: Regional lymph nodes (lymph nodes near
the pancreas) are not involved.
• N1: Cancer has spread to regional lymph nodes.
M categories
• MX: Spread to distant organs cannot be
assessed.
• M0: The cancer has not spread to distant lymph
nodes (other than those near the pancreas) or to
distant organs such as the liver, lungs, brain, etc.
• M1: Distant metastasis is present.
41. Stage Grouping
Stage 0 (Tis, N0, M0): The tumour is confined to the top layers of pancreatic duct cells and has not invaded deeper
tissues. It has not spread outside of the pancreas. These tumours are sometimes referred to as pancreatic
carcinoma in situ or pancreatic intraepithelial neoplasia III (PanIn III).
Stage IA (T1, N0, M0): The tumour is confined to the pancreas and is less than 2 cm in size. It has not spread to
nearby lymph nodes or distant sites.
Stage IB (T2, N0, M0): The tumour is confined to the pancreas and is larger than 2 cm in size. It has not spread to
nearby lymph nodes or distant sites.
Stage IIA (T3, N0, M0): The tumour is growing outside the pancreas but not into large blood vessels. It has not
spread to nearby lymph nodes or distant sites.
Stage IIB (T1-3, N1, M0): The tumour is either confined to the pancreas or growing outside the pancreas but not
into nearby large blood vessels or major nerves. It has spread to nearby lymph nodes but not distant sites.
Stage III (T4, Any N, M0): The tumour is growing outside the pancreas into nearby large blood vessels or major
nerves. It may or may not have spread to nearby lymph nodes. It has not spread to distant sites.
Stage IV (Any T, Any N, M1): The cancer has spread to distant sites.
42. 5 Year Survival
Stage
IA: 37%
Stage
IB 21%
Stage
IIA 12% Stage
IIB
6% Stage
III
2%
Stage
IV
1%
Increasing stage = worse 5 year survival
43. Complications
• Up to 30%
• Include: pancreatic fistula
– intraabdominal sepsis
– delayed gastric emptying
• Mortality < 5%
Diener et al. Ann of Surg; 2007;245(2);187-200
44. Mortality
• Resection is only option for cure
• Mortality in high volume centres less than 5%
• Clear evidence that high volume centres have better outcome
Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg. 1997;226:248–257.
Bassi C, Falconi M, Salvia R, et al. Management of complications after pancreaticoduodenectomy in a high volume centre: results on 150 consecutive patients. Dig Surg. 2001;18:453–457.
Gouma DJ, van Geenen RC, van Gulik TM, et al. Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume. Ann Surg. 2000;232:786–795.
Yuman Fong, MD, Mithat Gonen, PhD, David Rubin, MS, Mark Radzyner, MBA, JD, and Murray F. Brennan, MD. Long-Term Survival Is Superior After Resection for Cancer in High-Volume Centers Ann Surg.
2005 October; 242(4): 540–547.
48. Mucinous tumours
• All mucinous pancreatic neoplasms are (believed) to
malignant or pre-malignant
• Frankly malignant (invasive + CIS) among resected:
– Main duct IPMN ≈25-80%
– Branch duct IPMN ≈0-30% (series at high end do not have
assx pts)
– MCN ≈5-20%
Tanaka et al. Pancreatology 2006
50. Growing problem
• CT increasing by 9% per yr
• CT abd/pelvis ≈ 30% of all CTs
• ≈1% of abdominal CTs show
pancreatic cystic lesion
• up to 70% of CPN referred to
3O centre asymptomatic
Brenner, NEJM 2007
An epidemic of incidental
asymptomatic pancreatic cysts.
51. Diagnostic evaluation
• Cross sectional imaging (CT/MRI)
– Modest diagnostic accuracy
• EUS
– Morphologic characterization poor
– FNA for cytology and CEA
• PET
– Does not appear to discriminate
Visser, AJR 2007
Brugge, Gastro 2004
Sperti, J GI Surg 2005
52. But why not intervene to prevent cancer?
• Risk of malignancy in small, asymptomatic
pancreatic cysts approximates mortality from
operative intervention
• i.e. Whipple in expert centres:
– 1-3% mortality
– 40-50% morbidity
53. Intl Consensus Conference
Sedai, Japan 2004
1. Main duct IPMN - resect
2. MCN - generally resect (younger women, usually
left sided resection with < morbidity)
3. Branch duct IPMN
– Resect if symptomatic, > 3cm, mural nodules, +
cytology, jaundice, ductal dilatation
– Observe if ≤3 cm, no sx, nor worrisome features
Tanaka et al. Pancreatology 2006
54. Pancreatic Endocrine Tumours
• Insulinoma (B cells)
• Glucagonoma (A cells)
• VIP
• Rare tumours which may give rise to overproduction of
peptide products
55. Malignant Tumours
• Spleen - mostly secondary involvement
• Non-Hodgkin’s Lymphoma - most common malignancy
• Spleen is the primary site
– 10% Hodgkin’s disease
– 30% of resected spleens (staging procedure) have (+) histology
• Hairy cell leukaemia
– Resect for symptomatic splenomegaly
• CML & CLL
– symptomatic splenomegaly (hypersplenism) = splenectomy