OESOPHAGEAL CANCER 3rd year SSU

1. Dr Bernard Stacey Southampton General Hospital OESOPHAGEAL CANCER3rd year SSU

2. INTRODUCTION • Incidence of adenocarcinoma of the oesophagus is fastest rising cancer in Western world • Majority present late when only palliation possible • Resection implies a major procedure and many have concurrent disease

3. Incidence of Oesophageal Cancers Blot WJ et al. JAMA 1991;265:1287-9

8. The lower oesophagus: pressure control mechanisms • Lower oesophageal sphincter • Crural diaphragm • Sling fibres of the stomach

9. Oesophageal wall histology Circular Longitudinal  distance in lower oesophagus

12. How??

13. How??

14. Oesophagitis as a cause of oesophageal shortening • Experimental oesophagitis • Distal peristaltic contractions disappear • LOS pressure  by 60% • Oesophagus 1-2cm shorter • Oesophageal compliance  by 30% • Largely recovered by 4 weeks Zhang X et al. Am J Physiol Gastrointest Liver Physiol; 2005

15. The longitudinal muscle of the oesophagus • Attached to hypopharynx and diaphragm • At lower end it blends with phreno-oesophageal ligament • More muscle bulk than circular muscle • Can shorten oesophagus by 5-6cm

21. Anatomy of the Esophagogastric Junction Mittal, R. K. et al. N Engl J Med 1997;336:924-932

22. The phreno-oesophageal ligament: Origin - fascia transversalis Insertion: oesophageal wall Rich in collagen and elastic fibres

23. The phreno-oesophageal ligament

24. Fatty infiltration

26. Obesity: challenges OGJ integrity • BMI and waist circumference correlates to  in: • intra-gastric pressure and • G-O pressure gradient • Also separation of LOS and crural diaphragm = perfect scenario for reflux

27. Does weight loss help reflux? • Remarkably little data! • Yes: Derby 1999 • 23 pts BMI >23, GORD 6/12 • - 80% lost wt and symptoms improved • r = 0.548, p<0.001 • No: Stockholm 1996 • 20 pts; pH study confirmed reflux • - no significant improvement despite mean of 10kg wt loss • Maybe: Amsterdam 2002 • 42 pts BMI 43 • - wt loss, no gastric distension improved • - with gastric distension  continued reflux

29. One extra oesophageal adenocarcinoma for every 5000 men over 60 treated

32. ?

33. Clinical consequences of GORD

34. Reflux - Barrett’s - Cancer

36. Barrett’s Oesophagus

38. Symptomatic GORD as a risk factor for oesophageal adenocarcinoma • Lagergren J. NEJM 1999; 340: 825-31 Oes Cardia Recurrent symptoms 7.7 2.0 ‘Long-standing’ reflux 43.5 4.4

42. The oesophagitis-metaplasia-dysplasia-adenocarcinoma sequence 95% don’t present 10% 3.5% 1.2% 100% of adults >30yrs Normal oesophagus Mild Oesophagitis Severe Oesophagitis Barrett’s Metaplasia months months days - weeks years Roleof chemoprevention ? 0.25% 0.08% 0.06% High Grade Dysplasia Adenocarcinoma Low Grade Dysplasia 2 - 5 years 0 - 3 years

43. ‘Natural history’ of HGD • 43% had Ca in resection specimen • 24% progressed to Ca during 2-46 months follow up • Ca incidence at 3 yrs • 56% if diffuse • 14% if focal HGD • Veterans’ study – 7.3 yrs F/U: 4 / 79  Ca in 1st year 12 / 75  Ca of whom 11 cured • But: single pathologist

44. Reflux, Barrett’s and cancer • ~10% of population have reflux • 10-15% of these have Barrett’s change (short > long segment) • These get adenocarcinoma at 0.5%/year • 40% of adenocarcinomas have no history of GORD • <5% of adenocarcinomas are known to have Barrett’s on presenting with symptoms of their cancer

45. Symptomatic GORD as a risk factor for oesophageal adenocarcinoma • Lagergren J. NEJM 1999; 340: 825-31 Oes Cardia Recurrent symptoms 7.7 2.0 ‘Long-standing’ reflux 43.5 4.4

47. Dysphagia • Weight loss • Nausea and vomiting • Pain uncommon (unless metastases)

48. AGE DISTRIBUTION

49. STAGING Stage TNM 1st seen 5yr surv 1 T1 N0 M0 10% 90% 2a T2/3 N0 M0 25% 50% 2b T1/2 N1 M0 3 T3 N1 M0 45% 15% Any T4 4 Any M1 20% 0%