Introduction to (Non- Colonic) Gastrointestinal Cancers

1. Introduction to (Non-Colonic)Gastrointestinal Cancers Clarence K.W. Wong MD FRCPC Associate Professor of Medicine Division of Gastroenterology, Royal Alexandra Hospital GI Tumour Group, Cross Cancer Institute Email: clarence.wong@ualberta.ca

2. Objectives • After this lecture, the student should have an understanding of: • Epidemiology, Presentation, Diagnosis and Approach to management of gastrointestinal cancers • Esophageal • Gastric • Pancreatic Introduction to Gastrointestinal Cancers

3. Why are GI Cancers important? Introduction to Gastrointestinal Cancers

4. GI Cancers • Most common cancers as a group • Early recognition may improve survival • Intervention to prolong life, cure or palliate Introduction to Gastrointestinal Cancers

5. 45% of colorectal Cancers die. Introduction to Gastrointestinal Cancers

6. Case Presentation 1 • A 62 year old male sees you because of long term heartburn and solid food dysphagia. • The dysphagia presented 6 months ago • There are no signs of GI bleeding • appetite has decreased • lost weight Introduction to Gastrointestinal Cancers

7. Case 1 • Examination revealed a prominent right supraclavicular lymph node • Barium swallow revealed an irregular stricture in the distal esophagus (apple core) • Endoscopy confirms a distal adenocarcinoma Introduction to Gastrointestinal Cancers

8. The patients asks: • What were the chances that he would be diagnosed with this cancer? • What are the risk factors? • Are there new tools to aid staging/diagnosis? • She had a history of Barrett’s and esophagitis • How do we screen for Barrett’s? Q1 Cdn: High risk family history not addressed fully. Only remarks on family with 2 first degree relatives with CRC. Average risk screening from age 50-74 US: Start at age 40 – colonoscopy every 5 years (first degree relative under age 60). Mother had cancer under age 60. Q2 Cdn: FOBT – no recommendations for family history addressed. US: Colonoscopy – as family history is positive and first degree relative under age 60 Q3 Cdn: FOBT from age 50-74 annually or biennially US: FOBT, Sig, Sig+FOBT, DCBE or colonoscopy starting age 50 – interval determined by test and assuming screening test was negative: FOBT annually Sig Q5y Sig + FOBT Q5y and Q1y respectively Colonoscopy Q10y DCBE Q5y Introduction to Gastrointestinal Cancers

9. Esophageal CancerIntroduction • Uncommon, but lethal cancer • Death/Diagnosis ratio approaches 1 • Higher Male:Female ratio (2.5 : 1) • 2 main types: • Squamous cell carcinoma (SCC) • Adenocarcinoma • Many lifestyle related risk factors Introduction to Gastrointestinal Cancers

10. Esophageal CancerIncidence and age Introduction to Gastrointestinal Cancers

11. 5 4 3 2 1 0 1978 1974 1982 1994 1998 1990 1986 Incidence-Esophageal AdenocarcinomaRising Fast • Largest rate increase among all cancers Rate per 100,000 Introduction to Gastrointestinal Cancers

12. What symptoms to ask about? • Progressive Dysphagia (solids) • Partial to full obstruction • Dyspepsia • Anorexia • Weight loss • Nausea/Vomiting • Anemia • Asymptomatic • By the time these symptoms show up it is stage 3 or 4. Someone with a new cancer has heartburn. Introduction to Gastrointestinal Cancers

13. Esophageal CancerRisk Factors • SCC • Smoking • EtOH • Vitamin deficiency • (Fe, vit A, riboflavin) • Nutrition • Low fruits/veggies, fish • High pickled foods • Diseases • Achalasia, lye/caustic injury • Adenocarcinoma • Obesity • GERD • Barrett’s esophagus Introduction to Gastrointestinal Cancers

14. Esophageal Cancer-AdenocarcinomaRole of GERD Odds ratios for esophageal adenocarcinoma according to reflux • 45x increase with frequent, long-standing, severe symptoms Lagergren et al. NEJM 1999. Introduction to Gastrointestinal Cancers

15. What is Barrett’s Esophagus? • A process of metaplasia • replacement of normal squamous epithelium by mucosa with goblet cells and a villiform surface • resembles intestinal mucosa Gastroesophagealjunction Length of columnar segment Squamocolumnar junction/Z-line Top of gastric folds Introduction to Gastrointestinal Cancers

16. Endoscopic Description and Landmarks • Identifying the endoscopic landmarks for the endoscopic recognition of Barrett’s esophagus. It is crucial to identify the gastroesophageal junction, the anatomic landmark which is frequently defined by the proximal margin of the gastric folds. Normally the squamocolumnar junction is located at the gastroesophageal junction. • Endoscopic Description and Landmarks • However, when the squamocolumnar junction is displaced proximal to the gastroesophageal junction, a segment of endoscopically visible columnar mucosa is evident. Introduction to Gastrointestinal Cancers

17. H & E Stain and Alcian Blue / PAS H & E Stain Alcian Blue / PAS Barrett’s esophagus histology 17 Looks like a stomach biopsy but it is actually esophagus Introduction to Gastrointestinal Cancers

18. H & E Stain and Alcian Blue / PAS The histologic hallmark of Barrett's esophagus is the identification of acid mucin-containing goblet cells (intestinal metaplasia). On routine hematoxylin and eosin staining, goblet cells are identified by the presence of a barrel-shaped cytoplasmic distention filled with mucin that has a gray-blue tinge on routine stain (left). Goblet cells stain intensely with the Alcian blue portion of the Alcian blue/PAS stain due to the presence of acid mucin. The cells between the goblet cells pick up or stain with the PAS portion of the Alcian blue/PAS stain due to the presence of neutral mucins. This combination of goblet cells and foveolar-type cells is characteristic of incomplete intestinal metaplasia. Introduction to Gastrointestinal Cancers

19. Barrett’s esophagus • Barrett’s esophagus ↓ • Low Grade dysplasia ↓ • High Grade dysplasia ↓ • Adenocarcinoma Introduction to Gastrointestinal Cancers

20. Carcinoma in situ Introduction to Gastrointestinal Cancers

21. Esophageal CancerDiagnosis • Noninvasive • Barium swallow/meal • “Upper GI series” • Invasive • Esophagogastroduodenoscopy (EGD) • “Gastroscopy” • Endoscopic ultrasound (EUS) (this is more for staging … this is after the cancer has already been diagnosed) Introduction to Gastrointestinal Cancers

22. Barium swallow Even this is subtle,…. Some Might say this Looks like a Regular Contraction. Introduction to Gastrointestinal Cancers

23. Esophageal CancerEndoscopy Introduction to Gastrointestinal Cancers

24. Esophageal/Pancreatic CancerDiagnosis: EUS • Convergence of endoscopy and ultrasound • Diagnostic with radial technology • T & N staging • Direct sampling of tissue with linear array technology • New gold standard Introduction to Gastrointestinal Cancers

25. Esophageal CancerEndoscopic Ultrasound Introduction to Gastrointestinal Cancers

26. Esophageal CancerScreening? • "screening" is applied to diagnostic testing of asymptomatic at-risk individuals • “Surveillance" pertains to the diagnostic evaluation of individuals who have been identified as having an increased risk for a disease • Currently NO guidelines for average risk screening for esophageal cancer • Consider 1 time EGD if: • Over 50 • Longterm, severe heartburn symptoms • ?Caucasian males Introduction to Gastrointestinal Cancers

27. Esophageal CancerHigher risk groups • GERD/Dyspepsia over age 50 • Barrett’s esophagus • Smokers/heavy alcohol consumption • Achalasia • Caustic injury • Obesity Introduction to Gastrointestinal Cancers

28. Esophageal CancerTherapy • Barrett’s surveillance (Q3 years) • Acid suppression • LGD aggressive surveillance (Q1 year) • Endoscopic Therapy • For early cancers or HGD → resection OR ablation • Palliative • Chemoradiation, Endoscopic stenting • Endoscopic Photodynamic therapy Introduction to Gastrointestinal Cancers

29. Esophageal/Gastric CancerTherapy • Cure/Palliation • Surgery • Chemoradiation • Endoscopic • Ablation • Stenting • Prevention of bleeding Introduction to Gastrointestinal Cancers

30. Palliation For palliations, we stent. If you don’t Have any esophagus – do gastric pullup Or gastric bypass where you remove The esophagus and bypass and hook it Up to the colon. Introduction to Gastrointestinal Cancers

31. Introduction to Gastrointestinal Cancers

32. Case Presentation 2 • A 60 year old woman sees you because of worsening epigastric pain • Has had this for many years but increasing severity X 3 months • Early satiety, weight loss, nausea • Recently, has noted black stools Introduction to Gastrointestinal Cancers

33. Case 2 • Barium swallow reveals a filling defect in the antrum • Gastroscopy reveals a mass that is confirmed as adenocarcinoma Introduction to Gastrointestinal Cancers

34. The patient asks • What was my risk for gastric cancer? • What were the risk factors? • Could I have been screened for this? • What are the tests and treatments to come? Introduction to Gastrointestinal Cancers

35. Gastric Cancer • Prior to 1950, this was the most common cause of cancer death in men and 3rd in women • Incidence has fallen dramatically, but still a global killer • Still highest incidence in: • Japan, China, S. America, E. Europe ( h. pylori or fish diet) Introduction to Gastrointestinal Cancers

36. Gastric CancerIncidence Introduction to Gastrointestinal Cancers

37. Gastric CancerSymptoms • Epigastric fullness • Nausea • Loss of appetite • Dyspepsia • Dysphagia (will get this if it is near GE junction) • Vomiting (gastric outlet obstruction) • Usually asymptomatic until late stages Introduction to Gastrointestinal Cancers

38. Gastric CancerRisk Factors • Helicobacter pylori • Low socioeconomic status • Poor nutrition • Reduced fresh fruit/veggies, ascorbic acid, beta carotene • Poor sanitation • ?smoking/EtOH • Atrophic gastritis Introduction to Gastrointestinal Cancers

39. The most important risk factor identified in the development of gastric cancer is infection of the stomach with the bacterial organism Helicobacter pylori. Studies with the Mongolian gerbil show that when infected with H. pylori, the gerbil develops gastritis that progresses to gastric cancer. Epidemiological studies further support the link between H. pylori and cancer of the distal stomach (i.e., antrum). The risk of developing gastric cancer is about 1 in 97 in infected individuals, compared to 1 in 750 in uninfected individuals, over a 30-year period. Thus, the risk of developing gastric cancer in H. pylori-infected individuals is about 8 times higher than in uninfected individuals. Introduction to Gastrointestinal Cancers

40. Introduction to Gastrointestinal Cancers

41. Gastric CancerScreening • No screening programs in N. America • In Japan, regular screening of age ≥50 • More early tumours found • Serologic markers? • None • CEA, CA 19-9, AFP studied – NOT helpful • Diagnosis • UGI series (barium) – false neg in lesions up to 1 cm • EGD – 95% accuracy Introduction to Gastrointestinal Cancers

42. Gastric Cancer: Dyspepsia 5 key decision points for visit #1 Visit #1 Uninvestigated dyspepsia No • Consider: • Cardiac • Hepatobiliary • Medication-induced • Dietary indiscretion • OtherTreat as appropriate (A) Yes Other causes? Legend No = Action (B) Yes Age? Alarm? • Investigate • (endoscopy recommended) = Decision No (C) Yes • See NSAID mini-management schema NSAID? No (D) Yes • Treat as reflux • (see mini-management • schema) Reflux? - van Zanten SJ, et al. CMAJ 2000 No (E) Yes • Treat as Hp positive (see mini-management schema) • Treat as Hp negative (see mini-management schema) No Hp? Introduction to Gastrointestinal Cancers

43. Gastric CancerDiagnosis • Labs • Anemia, iron deficiency • Low Hb, Low MCV, Low ferritin, Low Fe • Noninvasive • Barium swallow • Invasive • EGD Introduction to Gastrointestinal Cancers

44. Gastric CancerBarium swallow Introduction to Gastrointestinal Cancers

45. Gastric CancerEndoscopy Introduction to Gastrointestinal Cancers

46. Gastric CancerTherapy • If superficial, can endoscopically resect (endoscopic mucosal resection) Introduction to Gastrointestinal Cancers

47. Gastric CancerTherapy • Early stage, but deeper tissue invasion – surgical resection Billroth I Billroth II This is newer and remove only Part of the stomach. Introduction to Gastrointestinal Cancers

48. Gastric CancerPalliation - stenting Introduction to Gastrointestinal Cancers

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50. Case Presentation 3 • A 68 year old man sees you because his eyes “look yellow” • He is otherwise asymptomatic although he has unintentionally lost weight Introduction to Gastrointestinal Cancers