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					     Gastric cancer

        Simon Dexter
 Consultant Upper GI surgeon
The General Infirmary at Leeds
                     Pathology

   Gastric cancer
       Adenocarcinoma
       GIST (gastro-intestinal stromal tumour)
       Carcinoid
       Lymphoma
       other
            Incidence of gastric carcinoma

                             16.9     20.4     52.8
                              6.8     11.5     25.3
12.4
  5.6         8.0                                       51.7      85.8
black         3.5                                       21.9      38.9
             white

                               3.9                7.3
                               1.5                4.3

                                                           14.1
          28.9                                              6.0
          26.4

   Male (top) and female age standardised rates per 100,000 per year
                                 Aetiology
   HP
        5 fold increase in incidence, 100% vs 0% infection
   Reflux disease
        Cardia cancer, Barrett’s cancer
   Risk factors
        Previous gastric surgery
             Bile gastritis
        Pernicious anaemia
             Chronic atrophic gastritis type A
                   3 – 5x risk of adenocarcinoma
        Family history
             Hereditary diffuse gastric cancer
                   CDH1 mutation (inactivates e-cadherin)
    Junctional cancer
   Increase in proximal
    gastric and GOJ cancer
   GOJ cancer (<5cm)
    classified by origin
        Siewert I
             Lower oesophageal
        Siewert II
             True GOJ
        Siewert III
             Proximal gastric
                Adenocarcinoma
             – Lauren classification
   Diffuse
       Linitis plastica type
       Poorer prognosis
   Intestinal
       Localised
       Better prognosis
       Distal stomach
T stage (UICC TNM 2002)

                 T3
        T2b

      T2a               T4
                 Adjacent
            T1   structure
    N & M stage (UICC TNM 2002)
   N stage                  M stage
       N0 - no nodes            M0 – no distant
       N1 - 1-6 nodes            metastases
       N2 - 7-15 nodes          M1 – distant
       N3 > 15 nodes             metastases (includes
                                  distant nodes)
         Early (T1) gastric cancer

   1970 – 1990
       Incidence of EGC increased from 1% to 15%
            Open access endoscopy
       46 cases
       Age 69 (38 – 86)
       98% 5 yr survival

                 Sue Ling et al (1992) Gut
    Current incidence of early gastric
                 cancer
   Leeds ~ 2%

   Tokyo > 50%
                        Presentation
   Early cancer                     Advanced cancer
       Asymptomatic                     Abdominal pain
       Anaemia                          Weight loss
       Dyspepsia 50%                    Epigastric mass
            May respond to PPI          Ascites
                                         Acanthosis nigricans
                                         Supraclavicular mass
                                         Dysphagia
                                         Jaundice
           Guidelines for referral

   2 week suspected cancer referral
       5% positive endoscopy


   NICE guidance, August 2004
       Management of dyspepsia in adults in primary
        care
Referral for endoscopy (NICE 2004)

   Review medications
   Urgent (<2 weeks) specialist referral for
    endoscopic investigation when dyspepsia with
       Chronic GI bleeding
       Progressive unintentional wt loss
       Progressive dysphagia
       Persistent vomiting
       Iron deficiency anaemia
       Epigastric mass
       Suspicious barium meal
Referral for endoscopy (NICE 2004)

    Routine endoscopy not necessary without alarm
     signs !!!
    Consider endoscopy when symptoms persist despite
     HP eradication or if patients have
         Prior gastric ulcer
         Prior gastric surgery
         Need for NSAID usage
         Raised gastric cancer risk
         Anxiety about cancer
    Empirical PPI therapy for other patients
       NICE dyspepsia guidance

   Not adequately researched
   No representation from upper GI surgeons
         Updated NICE guidance
             (August 2005)
   New onset dyspepsia age >55 requires
    endoscopy
     Investigations for patients with
              gastric cancer
   Endoscopy & biopsy

   Performance status
   Physiological assessment
       Cardio-pulmonary function

   CT chest & abdomen
   EUS (endoscopic ultrasound)
   Laparoscopy
                        CT scanning
   Technique
       Spiral CT of chest and
        abdomen
     Treatment of gastric cancer
   Endoscopic treatment
       EMR (endoscopic mucosal resection)
       ablation
   Surgery
   Multimodal treatment
       Neo-adjuvant
       Adjuvant
   Palliative treatment
    Endsocopic mucosal resection
   T1 mucosal disease
       Minimal risk of LN
        metastases
   Various techniques
   Specimen obtained
                  Surgery

   Total gastrectomy
   Subtotal gastrectomy
Gastric vascular anatomy
          Lymph node metastasis

   Radial spread
   D1 nodes
       Perigastric nodes
   D2 nodes
       Hepatic, splenic, coeliac
   D3 nodes
       Para-aortic nodes
                Stomach resection

   Total gastrectomy
   Subtotal
    gastrectomy
   Lymphadenectomy
       D1, D2, D3 etc
   Total
gastrectomy
   Whole stomach
    resected
   Duodenum
    oversewn
   Small bowel
    reconstruction
    Results of therapy – stomach cancer

   Surgery with curative intent
       42% of patients
   5 year survival – 60%
       Node positive - 35%
       Node negative - 88%



                              Sue Ling et al (1993) BMJ
                 Multimodal therapy
   Adjuvant chemotherapy             Neo-adjuvant
       Possible small advantage       chemotherapy (ECF)
       OR 0.84 (0.74 – 0.96)             MAGIC trial
       Western 0.96                           Surgery +/- chemo
       Asian 0.58                        503 patients
            Janunger 2001                Higher curative resection
                                           rate
                                               79% vs 69%
                                          Better survival at 2 years
                                               48% vs 40%
        Palliative chemotherapy

   Median survival benefit 3 – 6 months
   Combination therapy superior
   50% gain improvement in QOL
         Consequences of surgery
   Weight loss
   Food restriction
   B12, calcium, iron deficiency
   Dumping
       Early
       Late hypoglycaemic
   Diarrhoea
   Gallstones
   Stomal ulceration
                     Stromal tumours
   GIST (Gastro-Intestinal Stromal Tumour)
       Presentation
            Incidental
            Bleeding
       Pathology
            Blend sheets of spindle cells
            Previously mistaken for leiomyomata
            Origin cell – interstitial cell of Cahal
            C-kit +ve
            Actin -ve
               Stromal tumours

   Prognostic factors
       Size (>4cm)
       Resection margins

       Mitoses
       Vacuoles on EUS
               Stromal tumours

   Surgical Treatment
       Excision with clear margins
       No lymphadenectomy required
   Non –surgical treatment
       Glivec (imatinib)
       Recurrence / inoperable
       ? Neoadjuvant / adjuvant
                        Glivec

   Imatinib
       C-Kit (cd117) receptor blocker
       Blocks abnormal tyrosine kinase activity
         Normal Gastric Mucosa
   Normal gastric
    mucosa -
    body/fundus
   Cell types : Mucus
    cells, Parietal, Chief
   Neuroendocrine cells :
    ECL cells
         Normal Gastric Mucosa
   Normal gastric
    mucosa - antrum
   Cell types : Mucus
    cells
   Neuroendocrine cells :
    G cells
        Gastric Carcinoid Tumours

   <1% of gastric tumours
   4-41% of GIT carcinoid tumours
   Most ECL/argyrophil cell origin (80%)
   3 clinico-pathological subtypes:
       Type 1, 2 & 3
        Gastric Carcinoid Tumours

   Type 1 : Hypergastrinaemia with
    Autoimmune chronic atrophic gastritis
    (Type A)
       Pernicious anaemia
   Type 2 : Hypergastrinaemia with
    hypertrophic gastropathy
       Zollinger-Ellison syndrome
   Type 3 : Sporadic, no relation to
    hypergastrinaemia
  Gastric Carcinoid Tumours :
           Rindi et al
n = 45       Type 1     Type 2    Type 3
Mc+/-SMc     26 (92%)   6 (86%)   3 (30%)
Musc Prop    1 (4%)     1 (14%)   3 (30%)
Serosa       1 (4%)     0         4 (40%)
Multiple     18 (64%)   6 (86%)   0
Solitary     10 (36%)   1 (14%)   10 (100%)
Metastases   0          2 (29%)   6 (60%)
        Type 1 Gastric Carcinoid

   Type 1 Gastric carcinoid tumours :
    associated with Type A Autoimmune
    Chronic Active Gastritis
   Autoimmune process leads to destruction
    and gradual atrophy of chief and parietal
    cells of body/fundus - sparing of
    body/fundic neuroendocrine cells
   Hypochlorhydria or achlorhydria
       Gastric Carcinoid Tumours

   Hyperplastic precursor sequence
   Hypergastrinaemia -- Neuroendocrine
    hyperplasia -- Dysplasia -- Neoplasia
   Pernicious anaemia only present in 20-
    46% of patients (latent effect)
   Natural history : most probably remain
    stationary; some regress and some
    metastasize
              Gastric lymphoma

   MALT lymphoma
       Usually associated with HP infection
       Responds to HP eradication
   Non MALT lymphoma
       Variable pathology
       Prognosis dependent on stage and cell type
       Surgery reserved for salvage

				
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