Cancergastri2008

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  • 1. Tumors of Stomach Lu Ning Asist professor The General Surgery Dep.
  • 2. Pathology
    • Gastric cancer
      • Adenocarcinoma
      • GIST (gastro-intestinal stromal tumour)
      • Carcinoid
      • Lymphoma
      • other
  • 3. Gastric Carcinoma: Epidemiology
    • Second most common carcinoma worldwide after lung cancer
    • Incidence in U.S.: 22,000 pts/year
    • Ratio men: women = 2:1
    • Population studies: environmental exposures + cultural + genetic factors influence predisposition
    • Environmental RF: Dietary nitrates, salted or smoked meat/fish,smoking, H.pylori infection
  • 4. Incidence of gastric carcinoma 16.9 6.8 14.1 6.0 3.9 1.5 28.9 26.4 12.4 5.6 8.0 3.5 51.7 21.9 7.3 4.3 52.8 25.3 20.4 11.5 Male (top) and female age standardised rates per 100,000 per year black white 85.8 38.9
  • 5. Gastric cancer
    • Incidence in U.S. 10/100,000
    • Incidence in Japan 78/100,000
    • 5-year survival in U.S. is 12%
    • 5-year survival in Japan in 53%
  • 6. 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)
  • 7. 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
  • 8. Borrmann System
  • 9. ADENOCARCINOMA OF THE STOMACH
    • Histological typing
      • Ulcerated carcinoma (25%)
        • Deep penetrated ulcer with shallow edges
        • Usually through all layers of the stomach
      • Polipoid carcinoma (25%)
        • Intraluminal tumors, large in size
        • Late metastasis
      • Superficial spreading carcinomas (15%)
        • Confinement to mucosa and sub-mucosa
        • Metastasis 30% at time of diagnosis
        • Better prognosis stage for stage
  • 10. ADENOCARCINOMA OF THE STOMACH
    • Histological typing
      • Linitis plastica (10%)
        • Varity of SS but involves all layers of the stomach
        • Early spread with poor prognosis
      • Advanced carcinoma (35%)
        • Partly within and outside the stomach
        • Represents advanced stage of most of the fore mentioned carcinomas
  • 11. Adenocarcinoma – Lauren classification
    • Diffuse
      • Linitis plastica type
      • Poorer prognosis
    • Intestinal
      • Localised
      • Better prognosis
      • Distal stomach
  • 12. Lauren System
    • Intestinal
      • Environmental
        • Gastric atrophy, intestinal metaplasia
      • Men > women
        • Increasing inc. w/ age
      • Gland formation
      • Hematogenous Spread
      • Microsatellite instability
      • APC gene mutations
      • p53, p16 inactivation
      • APC , adenomatous polyposis coli
    • Diffuse
      • Blood type A
      • Women > men
        • Younger age group
      • Poorly differentiated, signet ring cells
      • Transmural / lymphatic spread
      • Decreased E-cadhedrin
      • p53, p16 inactivation
  • 13. Gastric Carcinoma
    • Diffuse
    • M:F 1:1
    • Onset Middle Age
    • 5 yr surv overall <10%
    • Aetiology
      • Diet
      • H. pylori
    • Intestinal
    • M:F 2:1
    • Onset Middle Age
    • 5 yr surv overall 20%
    • Aetiology
      • Unknown
      • Blood group A association
      • H. pylori
  • 14. T stage (UICC TNM 2002) T4 T3 T2a T1 Adjacent structure T2b
  • 15. T stage (UICC TNM 2002) Tumor invades adjacent structures T4 Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures T3 Tumor invades subserosa T2b Tumor invades muscularis propria T2a Tumor invades muscularis propria or subserosa T2 Tumor invades lamina propria or submucosa T1
  • 16. N & M stage (UICC TNM 2002)
    • N stage
      • N0 - no nodes
      • N1 - 1-6 nodes
      • N2 - 7-15 nodes
      • N3 > 15 nodes
    • M stage
      • M0 – no distant metastases
      • M1 – distant metastases (includes distant nodes)
  • 17. 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
  • 18. Current incidence of early gastric cancer
    • Tianjin ~ 2%
    • Tokyo > 50%
  • 19. Clinical Presentation
    • Asymptomatic
    • Early
      • Vague epigastric discomfort / indigestion
      • Pain is constant, nonradiating, unrelieved by food digestion
    • More advanced disease
      • Weight loss
      • Anorexia
      • Fatigue
      • Emesis
    • Symptoms dependent on location
      • Proximal
      • Distal
      • Diffuse
    • GI bleeding, obstruction
  • 20.
    • Physical signs – late
      • Assoc. w/ locally advanced or mets
      • Palpable abdominal mass
      • Palpable supraclavicular (Virchow’s) LN
      • Palpable periumbilical (Sister May Joseph’s) LN
      • Peritoneal mets palpable by rectal exam (Blumer’s shelf)
      • Palpable ovarian mass (Krukenberg’s tumor)
      • S/Sx of hepatomegaly
    Clinical Presentation
  • 21. Guidelines for referral
    • 2 week suspected cancer referral
      • 5% positive endoscopy
    • NICE guidance, August 2004
      • Management of dyspepsia in adults in primary care
  • 22. 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
  • 23. 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
  • 24. NICE dyspepsia guidance
    • Not adequately researched
    • No representation from upper GI surgeons
  • 25. Updated NICE guidance (August 2005)
    • New onset dyspepsia age >55 requires endoscopy
  • 26. Investigations for patients with gastric cancer
    • Endoscopy & biopsy
    • Performance status
    • Physiological assessment
      • Cardio-pulmonary function
    • CT chest & abdomen
    • EUS (endoscopic ultrasound)
    • Laparoscopy
  • 27. CT scanning
    • Technique
      • Spiral CT of chest and abdomen
  • 28. Treatment of gastric cancer
    • Endoscopic treatment
      • EMR (endoscopic mucosal resection)
      • ablation
    • Surgery
    • Multimodal treatment
      • Neo-adjuvant
      • Adjuvant
    • Palliative treatment
  • 29. Endsocopic mucosal resection
    • T1 mucosal disease
      • Minimal risk of LN metastases
    • Various techniques
    • Specimen obtained
  • 30. Gastric carcinoma: Surgical treatment
    • Total gastrectomy with Roux-en-Y reconstruction
      • Proximal and midbody tumors
    • Subtotal gastrectomy with Billroth II
      • Distal tumors
      • Resection of ¾ of the stomach
      • 5-6 cm resection margin when possible
  • 31. Gastric carcinoma: Lymphadenectomy
    • Role remains controversial
    • Current recommendation is D1 dissection
    • D1: removal of all nodal tissue within 3 cm of the primary tumor
    • D2: D1 + removal of hepatic, splenic, celiac, and left gastric lymph nodes; involves splenectomy and partial pancreatectomy to remove parasplenic and parapancreatic nodes when these are drainage sites of primary
    • D3: D2 + removal of para-aortic nodes
  • 32.  
  • 33. Lymph node metastasis
    • Radial spread
    • D1 nodes
      • Perigastric nodes
    • D2 nodes
      • Hepatic, splenic, coeliac
    • D3 nodes
      • Para-aortic nodes
  • 34. Stomach resection
    • Total gastrectomy
    • Subtotal gastrectomy
    • Lymphadenectomy
      • D1, D2, D3 etc
  • 35.  
  • 36.  
  • 37. Gastric carcinoma: Lymphadenectomy
    • Japanese literature shows survival benefit of extended D2 dissection:
      • Kodama and associates 1981
      • 39% 5 year survival after D2 vs. 18% for D1
    • Western literature shows no survival benefit but increased morbidity and mortality of D2 dissection
  • 38. 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
  • 39. Multimodal therapy
    • Adjuvant chemotherapy
      • Possible small advantage
      • OR 0.84 (0.74 – 0.96)
      • Western 0.96
      • Asian 0.58
        • Janunger 2001
    • Neo-adjuvant chemotherapy (ECF)
      • MAGIC trial
        • Surgery +/- chemo
      • 503 patients
      • Higher curative resection rate
        • 79% vs 69%
      • Better survival at 2 years
        • 48% vs 40%
  • 40. Palliative chemotherapy
    • Median survival benefit 3 – 6 months
    • Combination therapy superior
    • 50% gain improvement in QOL
  • 41. Consequences of surgery
    • Weight loss
    • Food restriction
    • B12, calcium, iron deficiency
    • Dumping
      • Early
      • Late hypoglycaemic
    • Diarrhoea
    • Gallstones
    • Stomal ulceration
  • 42. 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
  • 43. Stromal tumours
    • Prognostic factors
      • Size (>4cm)
      • Resection margins
      • Mitoses
      • Vacuoles on EUS
  • 44. Stromal tumours
    • Surgical Treatment
      • Excision with clear margins
      • No lymphadenectomy required
    • Non –surgical treatment
      • Glivec (imatinib)
      • Recurrence / inoperable
      • ? Neoadjuvant / adjuvant
  • 45. Glivec
    • Imatinib
      • C-Kit (cd117) receptor blocker
      • Blocks abnormal tyrosine kinase activity
  • 46. 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