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  • Pancreatic Adenocarcinoma

  • Anatomy

  • Anatomy

  • Arterial Supply

  • Venous Anatomy

  • 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)

  • 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

  • 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

  • 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

  • Insulin

    Major stimulants

    Glucose, amino acids, glucagon, GIP, CCK, sulfonylurea compounds, -Sympathetic fibers

    Major inhibitors

    somatostatin, amylin, pancreastatin, -sympathetic fibers

  • 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, -Sympathetic fibers

    Major inhibitors Glucose, insulin, somatostatin, -sympathetic fibers

  • 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

  • Pancreatic adenocarcinoma

    Head of Pancreas Tumour Tail of Pancreas Tumour

  • 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 doesnt cause symptoms in early stages

  • 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

  • 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

  • Demographics

    0

    200

    400

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    800

    0-4

    5-9

    10

    -14

    15

    -19

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    -24

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    -34

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    -54

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    -59

    60

    -64

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    -69

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    -74

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    -79

    80

    -84

    85

    +

    Age at diagnosis

    Nu

    mb

    er

    of

    ca

    se

    s

    0

    25

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    75

    100

    Ra

    te p

    er

    10

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    00

    po

    pu

    lati

    onMale cases

    Female cases

    Male rates

    Female rates

    Figure 1.2: Numbers of new cases and age-specific incidence rates,

    by sex, pancreatic cancer, UK 2003

  • Mortality

    0

    2

    4

    6

    8

    10

    12

    14

    19

    75

    19

    78

    19

    81

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    99

    20

    02

    Year of diagnosis

    Ra

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    0,0

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    on

    males incidence

    females incidence

    males mortality

    females mortality

    Figure 1.3: Age standardised (European) incidence and mortality

    rates, pancreatic cancer, by sex, GB, 1975-2004

  • Mortality

    0

    10

    20

    30

    40

    50

    one-year five-year one-year five-year

    % s

    urv

    iva

    l

    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

  • 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)

  • Clinical presentation

    Weight loss

    Anorexia

    Nausea & vomiting

    Abdominal pain

    Obstructive jaundice (head lesions)

    Cachexia

    Very difficult to diagnose in early stage

  • 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&Es

    Tumour marker: CA 19-9

    Laparoscopy

  • CT

  • MRCP

  • 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

  • Staging Laparoscopy

    1. John et al. Annals of Surg 1995; 221: 156-164

    Peritoneal Seedlings

    ASCITES

  • EUS

  • EUS small tumours

    pancreas

  • Staging and biopsy

    CBD: common bile duct; PV: portal vein; HOP: Head of pancreas

    Biopsy Needle

  • Treatment

    Resection possible in only approx 20%

    local invasion

    Metastases

    advanced cachexia

    Resection Whipple procedure

    Unresectable biliary bypass + gastric bypass

  • Allen Oldfather Whipple (1881-1963)

    Original paper. Whipple AO, Parsons WB, Mullins CR. Treatment of Carcinoma of the Ampulla of Vater. Ann Surg 1935; 102: 763-769.

  • Whipple's Procedure

  • Whipple pancreaticoduodenectom

  • Pancreatic Anastomosis

    Jejunum

    Cut end of pancreatic neck

  • Biliary Anastomosis

  • Gastric Anastomosis

  • 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 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.

  • T Stage

  • Lymph nodes

  • Metastases

  • 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 ma

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