Gastric and Oesophageal Cancer

Trends in cancer mortality, England and Wales SMR base 1980

Oesophagogastric Cancer The National Problem 5th commonest malignancy 4th commonest cause of death 13,500 people in 2010 5 year survival - oesophageal 10% 5 year survival - gastric 15%

Oesophagogastric Cancer The Local Problem North Trent Cancer Network – Population 1.8m 30 October 2007 – 30 June 2009 744 cases of oesophagogastric cancer 155 resections (21%) 1 year survival Resected 77% Palliative oncology 34% Best supportive care 18%

Symptoms Physical signs Dysphagia Vomiting GI bleed Symptoms of anaemia Weight loss Dyspepsia Reflux

Physical Examination Anaemia Malnutrition Supraclavicular lymphadenopathy Pleural effusion / consolidation Hepatomegaly Ascites Vocal cord paralysis

Physical Signs Sister Mary Joseph’s Nodule 7

Physical Signs Virchow’s Node - Troisier’s Sign 8

Epidemiology Marked increase in the incidence of lower 1/3 oesophageal and G-O junction adenocarcinoma in last 20 years Corresponding decrease in the incidence in distal gastric cancer and squamous cell cancer of the oesophagus.

Oesophageal Cancer Aetiology Smoking Alcohol G-O reflux Barrett’s oesophagus

Why?

Evolution of Barrett’s and Oesophageal Cancer months months months/years 95% don’t present Normal oesophagus 100% Mild oesophagitis 10% Severe oesophagitis 3.5% Barrett’s 1.6% years CARCINOMA 0.08% High Grade Dysplasia 0.12% Low Grade Dysplasia 0.35% 0 – 3 years 2 - 5 years Life time risk of oesophageal cancer: Male 5% Female 3%

oesophageal carcinoma Aetiology oesophageal carcinoma Carcinogens - alcohol, tobacco SCC>ACA Chronic irritation - corrosives SCC - achalasia SCC - columnar metaplasia (Barrett’s) - iron deficiency anaemia Genetic - tylosis SCC Geographic - ? genetic ? environmental Infection - bacteria, fungi, viruses (human papillomavirus) Radiotherapy

Relative risk of developing oesophageal cancer Alcohol and Smoking Relative risk of developing oesophageal cancer Smoking cigarettes/day RR <15 2.0 15-24 3.9 >25 6.2 Alcohol units/day RR 4-8 2.1 >8 3.6 Very heavy smoking & drinking 12.0 RR: spirits > beer/wine

Oesophageal carcinoma Geographical variation in incidence (per 100,000 pa) Europe - Scotland 10 - England 8 - France (overall) 12 Brittany / Normandy 30 USA - Caucasian 5 - Afro-Caribbean 17 South Africa - overall 6-37 Transkei 70 Asia - Iran 38-110 - China Henan 38-140 Yangcheng 169

1953 - 78 1980 - 88 Resections (%) 39 56 Operative mortality (%) 29 13 1 year survival (%) 18 56 2 year survival (%) 9 34 5 year survival (%) 4 20

Medically fit No metastases Operate Resectable Medically unfit Metastases Palliate Unresectable

Assessment *Endoscopy *C.T. Scan *PET Scan *Endoscopic ultrasound Ultrasound/MRI Laparoscopy Barium swallow Bronchoscopy

C.T. Scanning No extra oesophageal disease Equivocal 3 Groups Obvious metastases/nodes

PET Scanning

PET Scanning

Restore Swallowing

Oesophageal Carcinoma Expandable Metal Stents Advantages - minimally invasive insertion - low complication rate - no stent migration - improved swallowing Disadvantages - tumour ingrowth - cost - short patient life expectancy

Chemo Radiotherapy

Surgical Approaches Abdomen & Right Chest (Ivor-Lewis) Transhiatal Minimally invasive

5 Year Survival Stage I 70% II 35% III 14% IV 6% Node - = 25 - 39%

MRC trial OEO2 Resectable Oesophageal Carcinoma SCC / ACA Randomised Chemotherapy + Surgery (CS) Surgery alone (S) n=400 n=402

Kaplan-Meier curve showing survival from date of randomisation CS S p=0.004 OE 02 Trial

Oesophageal carcinoma Conclusions Incidence is increasing Selection of patients for surgery has improved Peri operative mortality rate has fallen Expandable metal stents have improved palliative treatment for unresectable carcinomas Use of neoadjuvant treatments may improve survival rates Long term outcome for patients with oesophageal carcinoma remains dismal

Gastric Cancer : Facts Incidence 16:100,000 10,000 new cases per annum Male: Female 2:1 Incidence decreasing ? Proximal cancers more common Survival remains poor Debate on surgical treatment

Environmental Factors Refrigeration Diet salt, nitrates, fruit and veg Smoking x 2 Alcohol Aspirin x 50% Low SE group

Gastric Cancer Helicobacter pylori Chronic gastritis Atrophic gastritis Intestinal metaplasia Dysplasia Carcinoma

Inherited Factors 1 FDR x2-3 10% familial clustering Twin studies FAP HNPCC Juvenile polyposis E Cadherin gene mutations (CDH1)

CDH1 Family Tree Familial Diffuse Gastric Cancer † 48 † 39 39 37 36 † 48

Aetiology of Gastric Cancer Napoleon Bonaparte 1769-1821 Diet: Full of salt preserved foods, very little fruit & vegetables – common foods for long military campaigns Genetic: father died of stomach cancer H.Pylori: Chronic H.Pylori infection Pre cancerous changes: CAG

Assessment Endoscopy position, size, type CT scanning IV contrast, oral water EUS T stage, N stage Laparoscopy peritoneal disease Fitness

Surgery Gastric resection Lymphadenectomy Reconstruction

Gastric Resections Roux-en-Y 52

Lymphadenectomy 53

D1 or D2 lymphadenectomy? UK MRC Trial Dutch Trial 737 patients 400 curative resections 200 D1 v 200 D2 Dutch Trial 1078 patients 711 curative resections 380 D1 v 331 D2

Dutch Trial 55

MAGIC Trial UK MRC Adjuvant Gastric Infusional Chemotherapy E epirubicin 3 cycles pre op C cisplatin 3 cycles post op F 5-FU

MAGIC Trial 1994 - 2000 Chemo & surgery 250 503 patients Surgery 253

MAGIC Trial Chemo-Surgery-Chemo Surgery Curative resections 79% 69% Morbidity 47% 45% Mortality 6%

MAGIC Trial Disease free survival Chemo-Surgery-Chemo Surgery 2 years 48% 40% 5 years 36% 23%

Gastric Cancer - Conclusions Incidence decreasing Pre-operative chemotherapy improves survival Better surgical results in specialist units Early diagnosis essential