Expert Gastroenterology Insights: CRC Screening to IBD Treatment

1. GI Board Review Steven Klein, MD Wilmington Gastroenterology

2. Pearls • Specialists write questions • Endoscopy usually the answer • Emphasis on outpt. Eval of common GI disorders • When to refer for endoscopic evaluation

3. Outline • CRC Screening/Hereditary cancer syndromes • Common UGI disorders • IBD • Abnormal Liver enzymes

4. Colorectal Cancer Screening • Risk Assessment • Family hx of CRC • Family hx of adenomatous colon polyps • Possible HNPCC/FAP • Important factors • First degree relatives • Age at diagnosis • Younger than 60?

6. Hereditary CRC Syndromes • HNPCC • Account for 2-3% of CRC • 50 -70 % risk of CRC, early in life (30’s) • Average number of polyps, but more aggressive • Germline mutation in MMR Gene • Associated Malignancies • Endometrial (70%) • Ovary,stomach,SI, panc, GU • Surveillence – colonoscopy every 1-2 yrs starting at age 20

9. Hereditary CRC Syndromes • Familial Adenomatous Polyposis • Autosomal dominant germline mutation APC • Greater than 100 polyps • Cancer risk 100% by age 45 • Attenuated version with fewer polyps • Management • Total proctocolectomy • Surveillence for extracolonic lesions – gastric/duodenal carcinoma, thyroid ca, CNS tumors

12. Hereditary CRC Syndromes • MUTYH Associated Polyposis • Autonomic recessive (MYH gene) • Similar to FAP • Peutz-Jeghers Syndrome • Autosomal Dominant • Pigmentation of buccal mucosa, harmatomatous polyps throughout GI tract

14. UGI Disorders • GERD • Emperic tx with PPI in those that are young without alarm symptoms • Endoscopy for those with alarm symptoms – age greater than 50, dysphagia, blood in stool, anemia, vomiting, hemetemesis, wt.loss, failure of sx. To respond to PPI

15. UGI Disorders • Barrett’s esophagus • Intestinal metaplasia of squamous epithelium • Caucasions, Hispanic >> Blacks,Asians • Male:Female 2:1 • 8-15% of those undergoing EGD for GERD • 5% in those without!!

17. UGI Disorders • Barretts • associated with dysplasia (1%) , adenocarcinoma (0.5%) • HGD – 4 – 6% risk of cancer within the year • Screening – chronic GERD, those > 50? • Scant evidence to support mortality benefit • Most people die for other reasons

18. UGI Disorders • Barretts • Screening controversisal • If found, 4 quadrant biopsy q 2 cm • Repeat endo in 1 year, if no dysplasia, then q 3 yrs • Low grade dysplasia – 6 months then yearly • High grade dysplasia – repeat endo in 3 months • Ablative techniques, vs. surgery

19. UGI Disorders • Dysphagia – difficulty swallowing • Oropharyngeal – neurogenic/myogenic origin • Esophageal – body, or LES, motility vs. obstruction • Solids vs liquids? • Odynophagia – pain with swallowing

21. UGI Disorders • Eosinophilic esophagitis • Young adults, hx. of atopy • Multiple rings, often present with food bolus obstruction

24. UGI Disorders • H. Pylori infection • 50% of world population • More prevalent in developing world • Acquired at early age • Associated diseases • Chronic gastritis • Duodenal ulcer • Gastric ulcer • Gastric cancer • dyspepsia

25. UGI Disorders • H Pylori – Diagnostic testing • Non invasive – urea breath test (most accurate), serology(perhaps best initial test) stool antigen • “test and treat” - dyspepsia, no alarm symptoms, young pt. • Invasive – CLO, histology – reserved for those undergoing diagnostic endoscopy • Confirm eradication – with breath test off PPI 1 month later for those with complications

27. IBD • Epidemiology • prevalence • CD 201 per 100,000 • UC 238 per 100,000 • Peak incidence • Between 15 – 30 yrs • Second peak between 50 – 80 • Smoking • Negative correlation with UC, positive for CD

28. IBD • UC • Chronic colonic inflammation limited to mucosa • Presentation • Mild – tenesmus, mucous, < 4 BM/day • Moderate – mild anemia, up to 10BM/day • Severe – fever, cramps, wt loss, >10 stools per day • Diagnosis • Hx. + endoscopy with bx • Chronic inflammation • Infectious, ischemic colitis in differential

29. IBD

30. IBD • Crohns Disease • Transmural inflammation – leading to fibrosis, obstruction, fistulae • Can involve the entire GI tract • Presentation • More variable than UC • Fatigue, abdominal pain, wt. loss. • 10% without diarrhea • Diagnosis • Chronic inflammation, skip lesion, granuloma

31. IBD

32. IBD • Treatment • Goals are induction and maintenance of remission • Similar for both UC/Crohns • Mild disease • Mesalamine, SSZ for colitis • Abx , entocort for CD • Moderate disease • Add steroids, consider immunomodulator (AZA/6MP)

33. IBD • Treatment • Severe Disease • Hospitalizaion • Consider TPN • IV Corticosteroids • Rapid improvement – add immunomodulator • Steroid Refractory • CD – biologic agent (infliximab), • UC – biologic, cyclosporine, surgery

34. IBD • Treatment • Fistulizing CD • No role for steroids • Abx, AZA/6MP, biologic • Surgery • UC – proctocolectomy with IPAA • CD – limited resection based on disease extent • No pouch • Extraintestinal Manifestations • 40% of pts

38. Elevated Liver Tests • Liver performs a wide variety of biochemical, synthetic, and excretory function • No one test provides a global assessment • Recognition of common patterns of abnormalities will help guide further evaluation

39. Markers of Hepatocyte Necrosis • Aminotransferases • Aspartate aminotransferase (AST/SGOT) • Not specific for liver – present in muscle, kidney, RBC • Present in both hepatocyte cytosol and mitochondria • Alanine aminotransferase (ALT/SGPT) • Relatively specific for liver • Present in the cytosol

40. Markers of Hepatocyte Necrosis • AST/ALT ratio • Usually less than or equal to one • Greater than 2 in several settings • ETOH – secondary to pyridoxine deficiency • Cirrhosis • Wilson’s disease (ratio greater than 4)

41. Markers of Hepatocyte Necrosis • AST and ALT levels • Levels < 500 are found in wide variety of liver diseases • Massive elevations (>2000 IU) are almost exclusively related to acute viral hepatitis, drug induced liver disease, or ischemia

42. Markers of Hepatocyte Necrosis • Lactate Dehydrogenase (LDH) • Very wide tissue distribution, so rarely helpful • Extreme elevation with ischemia (greater than 5000 IU)

43. Markers of Cholestasis • Alkaline phospatase (AP) • Present in a variety of tissues (liver, bone, intestine, leukocytes) • Elevation results from increased synthesis induced by cholestasis • Striking elevations seen in infiltrative liver disease, intra or extrahepatic biliary obstruction

44. Markers of Cholestasis • Gamma Glutamyl Transpeptidase (GGTP) • Also found in a variety of other tissue, but not bone • Can confirm hepatic origin of elevated AP • Induced by EtoH and drugs – GGTP/AP ratio > 2.5 suggests EtoH

45. Markers of Cholestasis • 5’ – Nucleotidase • Again has wide tissue distribution, but sig elevations are fairly specific for liver disease • Less sensitive compared to GGTP to confirm hepatic origin of elevated alk phos

46. Markers of Cholestasis • Bilirubin • Product of heme metabolism • Serum concentration usually < 1mg/dl, is unconjugated • Normally, less than 5% conjugated • Jaundice evident with bilirubin > 3

47. Markers of Cholestasis • Hyperbilirubinemia • Impaired biliary excretion – conjugated hyperbilirubinemia • Biliary obstruction • With choledocholithiasis, bilirubin rarely exceeds 8 mg/dl • Hepatocellular disease • Increased production usually results in an unconjugated hyperbilirubinemia • Hereditary disorders of bilirubin metabolism

49. Markers of Synthetic Capacity • Prothrombin Time (PT) • Liver synthesizes all coagulation factors except VIII • Vit K required for carboxylation of II, VII, IX, X • Diff dx of prolonged PT includes Vit K def, DIC, and Liver disease • Measurement of factor VIII is low in DIC, nml or high in liver disease • If malabsorption, Vit K should reduced the PT by 30% within 24 hrs

50. Markers of Synthetic Capacity • Albumin • About 10gm synthesized and secreted by hepatocytes daily • Synthesis decreases with progressive liver disease • Other factors such as nutrition, renal or GI losses, important as well • Half life of 20 days, so less helpful for acute liver disease