Gastroenterology and Hepatology Board Review

1. Gastroenterology and HepatologyBoard Review Jeff Singerman June 13, 2007

2. Question 1 • A 57-year-old man is evaluated because of persistent serum aminotransferase elevations. Medical history is significant for stage II colon CA that was resected 6 years ago. There has been no evidence of recurrence. The patient has been taking atorvastatin for 5 years for management of hyperlipidemia. He recently required amox/clav for the treatment of acute sinusitis, which has resolved. He drinks 3-4 glasses of wine on weekends. PE discloses only mild hepatomegaly. BMI is 32. • Labs: Glc-124, LDL-122, HDL-56, Tri-185, AST-92 (was normal 2 years ago, 87 1 year ago), ALT-104 (was normal 2 years ago, 106 1 year ago), AP-62, Bili-0.7, Albumin-4.5, INR-1.1 • CT scan of the abdomen shows low-density hepatic parenchyma.

3. Question 1 continued • Which of the following is most likely causing this patient’s elevated serum aminotransferase values? • Recurrence of colon cancer • Nonalcoholic fatty liver disease • Administration of amoxicillin/clavulanate • Primary biliary cirrhosis • Alcohol use

4. Non-Alcoholic Fatty Liver Disease (NAFLD) • Spectrum of disorders characterized by predominantly macrovesicular hepatic steatosis that occur in individuals even in the absence of consumption of alcohol.

5. Non-Alcoholic Fatty Liver Disease (NAFLD) • Risk Factors: Obesity, DM, dyslipidemia, severe weight loss, some drugs • Drugs: Amiodarone, Tamoxifen, Glucocorticoids, synthetic estrogens • Evaluation: LFTs, Hep B, Hep C, EtOH hx • Imaging: US, CT, or MRI • All can detect steatosis and rule out other causes • Cannot distinguish between fatty liver, steatohepatitis, and steatohepatitis with fibrosis • Confirmation: Liver biopsy • Treatment: Weight loss

6. NAFLD and NASH

7. Non-Alcoholic Steatohepatitis (NASH) • Subset of NAFLD • Liver bx showing moderate to gross macrovesicular fatty changes (with or without fibrosis or cirrhosis) • Negligible EtOH consumption (<40 g/week) • Absence of infectious hepatitis (Hep B, Hep C) • Risk Factors: Obesity, DM, hyperlipidemia

8. Non-Alcoholic Steatohepatitis (NASH) • Diagnosis • Most are asymptomatic • Fatigue, malaise, vague RUQ discomfort • Hepatomegaly • Elevated LFTs (although can be normal in advanced fibrosis) • Confirmation: Liver biopsy

9. Non-Alcoholic Steatohepatitis (NASH) • Progression to cirrhosis in 8-26% • Predictors of fibrosis: • Age > 45 or 50 • BMI > 28 • Triglycerides > 1.7 mmol/L • ALT > 2 x normal • AST:ALT > 1 • Treatment: none proven • Weight loss • Insulin sensitizers: metformin, rosiglitazone, pioglitazone

10. Question 2 • A 66-year-old woman comes for her annual physical examination. She reports only mild fatigue. The patient has prediabetes that is managed by diet alone. She takes no meds and drinks one glass of wine each day. On exam, BP 132/86, BMI is 32, otherwise normal. • Labs: Hb-13.1, Plt-85, Glc (fasting)-119, lipids-nl, AST-138, ALT-124, AP-50, Bili-0.8, Alb-3.1, Hep A,B,C-negative, Transferrin-nl, UA-nl • Abd US: evidence of mild fatty infiltration of the liver.

11. Question 2 continued • In addition to weight loss, which of the following is the most appropriate next step for managing this patient’s liver chemistry abnormalities? • Rosiglitazone; repeat liver tests in 6 months • Alcohol counseling • Liver biopsy • Evaluation for liver transplantation

12. Question 3 • A 24-year-old man has intermittent dysphagia for solid foods that has required two visits to the emergency department in the past 6 years for endoscopic removal of pieces of chicken. The patient has no weight loss or heartburn. He has always been a slow eater. He has mild asthma and uses a beta-agonist inhaler intermittently. On exam, the patient is well developed. General exam is normal. EGD reveals some mild ring formation in the mid-esophagus. Esophageal biopsy specimens show intense eosinophilic infiltration.

13. Question 3 continued • Which of the following is the most appropriate therapy for this patient’s dysphagia? • A long-term PPI • Topical swallowed corticosteroids • Oral nifedipine before meals • Sublingual nifedipine before meals

14. Eosinophilic Esophagitis • A new diagnosis with accelerating incidence • Characterized by eosinphilic infiltration of the esophagus • Unclear etiology: allergic?

15. Eosinophilic Esophagitis • Epidemiology: In adults, most commonly seen in males, age 20-30 • Clinical Characteristics • Dysphagia ± morphologic abnormalities • Strictures (most common, usually proximal) • Rings (occasionally multiple) • Linear furrows • “Feline esophagus” • “Too-small esophagus” • Food impaction • Esophageal dysmotility (occasionally) • History of asthma and peripheral eosinophilia

16. Eosinophilic Esophagitis • Diagnosis: consensus not yet achieved 1) Presence of characteristic clinical findings 2) Presence of large number of eosinophils in the esopghagus • Usually > 20 eos/hpf (GERD usually < 5 eos/hpf) 3) Exclusion of other causes

17. Eosinophilic Esophagitis

18. Eosinophilic Esophagitis • Treatment: • Swallowed Steroids (fluticasone MDI) • Esophageal Dilation (carefully) • Elimination Diets (unclear utility in adults) • Acid suppression usually not helpful

19. Question 4 • A 53-year-old woman has a 6-month history of increasing diarrhea without bleeding or a sense of urgency. She has 3 or 4 bowel movements daily compared with her previous pattern of two or three bowel movements each day. The patient has lost 6 pounds during this time. Medical history is significant for hypothyroidism, managed with thyroid replacement therapy. The patient is post-menopausal and has had no abnormal vaginal bleeding. She has maintained a lifelong milk-free diet. Physical exam is normal. BMI is 21 • Labs: Hb-9.8 (was 13.5 1 year ago), WBC-6.5, Plt-250, MCV-85, RDW-19 (elevated), Ferritin-10, Alb-4.5, LFTs-nl, TSH-nl, Anti-TTG Ab-negative, Stool cultures/c. dif/O and P are negative • Upper GI series with small-bowel follow-through is normal. Colonoscopy with random biopsies is also normal

20. Question 4 continued • Which of the following diagnostic studies should be scheduled next? • Antiendomysial antibody assay • Serum calcitonin measurement • Upper endoscopy with small bowel biopsies • Serum gastrin measurement • Capsule endoscopy

21. Celiac Disease • All testing must be done on a gluten-containing diet • Serum Antibody Assays • IgA Endomysial Ab • Sensitivity 85-98%, Specificity 97-100% • IgA TTG Ab • Sensitivity 93%, Specificity 99% • IgA Antigliadin Ab • Sensitivity 75-90%, Specificity 82-95% • IgG Antigliadin Ab • Sensitivity 69-85%, Specificity 73-90% • Antigliadin antibodies no longer recommended for screening or diagnosis except in cases of IgA deficiency

22. Celiac Disease

23. Celiac Disease • Anemia and Celiac Disease • Iron deficiency is common (can be the only manifestation of celiac in adults). • Due to malabsorption rather than GI blood loss • Macrocytic anemia can be seen as well • Usually secondary to folate deficiency, B12 deficiency is rare • With both entities, can see a normocytic anemia with an increased RDW.

24. Steroids in Alcoholic Hepatitis • Controversial • 12 controlled trials performed • 5 showed reduced mortality vs. placebo • 7 showed no difference vs. placebo • 3 metanalyses • 2 showed a beneficial effect • 1 showed benefit or harm depending on subgroup

25. Steroids in Alcoholic Hepatitis • ACG Guidelines: • Corticosteroids should be used in patients with severe alcoholic hepatitis and/or hepatic encephalopathy • Severe described by prothrombin discriminate function > 32 • [4.6 x (prothrombin time above control in seconds) + Bili] • The efficacy of steroids has not been adequately studied in patients with severe alcoholic hepatitis who also have: • Concomitant pancreatitis • Renal failure • GI bleeding • Active infection • Histological confirmation of alcoholic hepaititis optimizes the selection of these patients. However, must be weighed against risk of performing biopsy

26. Steroids in Alcoholic Hepatitis • Treatment: • Prednisolone 40mg daily x 4 weeks followed by a taper • Prednisone is not used as is converted to predisolone in the liver • Reduces mortality by 25% • Although mortality remains as high as 44% in patients receiving steroids • NNT = 7

27. Cholecystectomy inAsymptomatic Cholelithiasis • There are no indications for cholecystectomy in asymptomatic cholelithiasis, with a few exceptions: • Many patients at increased risk for biliary CA should get prophylactic cholecystectomy or incidental cholecystectomy at time of other intra-abdominal surgery. • Choledocal cysts • Caroli’s Disease • Anomalous pancreatic ductal drainage (into CBD) • Gallbladder adenomas • Porcelain gallbladder

28. Cholecystectomy inAsymptomatic Cholelithiasis • Sickle Cell Disease • Pigmented stones are common and often asymptomatic • Not an indication for prophylactic cholecystectomy, but may be taken out incidentally during another procedure • Hereditary Spherocytosis • Bilirubin stones • Indication for prophylactic or incidental cholecystectomy • Gastric Bypass Surgery • Incidental cholecystectomy recommended at the time of surgery

29. Cholecystectomy inAsymptomatic Cholelithiasis • Diabetes Mellitus • Increased risk for developing severe gangrenous cholecystitis • However, prophylactic cholecystectomy is not recommended secondary to increased risk of surgery.

30. Colon Cancer Screening • Average risk patients: • Offer one of the following beginning at age 50 • FOBT yearly • Sigmoidoscopy q5yrs • Combined FOBT/Sigmoid q1yr/q5yrs • Colonoscopy q10yrs (no trials) • Double Contrast Barium Enema q5yrs (no trials)

31. Colon Cancer Screening • Family history of colon CA • 1st degree relative with colon CA or adenomatous polyps on bx age < 60 OR two 1st degree relatives dx with colorectal CA at any age • Colonoscopy at age 40 or 10 years earlier that the earliest diagnosis in their family, whichever comes first • Repeat colonoscopy every 5 years • 1st degree relative with colon CA or adenomatous polyp dx age > 60 OR two 2nd degree relatives with colon cancer • Screen like average risk patients but start at age 40

32. Colon Cancer Screening • Personal History of Polyps • 1-2 small (<1 cm) tubular adenomas with only low-grade dysplasia • Colonoscopy every 5-10 years • 3-10 adenomas or any adenoma > 1cm, or any adenoma with villous features or hi-grade dysplasia • Colonoscopy every 3 years • >10 adenomas • Colonoscopy more frequent than every 3 years, determined by clinical judgment • Sessile adenomas that are removed piecemeal • Colonoscopy at 2-6 months to verify complete removal

33. Colon Cancer Screening • Personal History of Colon CA resection: • Pre-op or peri-op colonoscopy on all patients • Subsequent colonoscopies at 3 years post surgery and then, if normal, every 5 years • For those patients with an obstructing mass: • Full colonoscopy within 6 months of surgery

34. Colon Cancer Screening • Familial syndromes • HNPCC • Begin at age 20-25, or 10 years earlier than youngest age of colon CA dx in the family, whichever comes first • Colonoscopy every 1-2 years • FAP • Begin at age 10-12 and continue until age 35-40 if negative • Flex sig or colonoscopy yearly • Classic FAP always isolated to rectosigmoid, attenuated FAP can be right sided • +/- genetic counseling and testing

35. Colon Cancer Screening • Inflammatory Bowel Disease • Ulcerative Colitis • AGA: colonoscopy after 8 years of diagnosis in patients with pancolitis and 15 years in patients with only left sided involvement; Repeat every 1-2 years • ACG: annual colonoscopy beginning after 8-10 years of diagnosis in patients who are surgical candidates. Evidence of definite dysplasia warrants referral for colectomy. • Crohn’s Disease • AGA: same as for UC • ACG: insufficient evidence for guidelines

36. Question 5 • A 40-year old woman has an 18-year history of UC that is limited to the left side and has responded well to therapy. Recent surveillance colonoscopy with biopsies showed low-grade dysplasia. Which of the following is the most appropriate next step? • Repeat colonoscopy in 3 months • Repeat colonoscopy in 1-2 years • Administer sulindac • Administer a low-dose corticosteroid • Refer for colectomy

37. Question 6 • A 32-year-old man comes for an annual health maintenance visit. His mother was diagnosed with colorectal cancer at 55 years of age. The patient reports no rectal bleeding or other symptoms. Medical history is noncontributory except for hypercholesterolemia. PE is normal. When should this patient first undergo colorectal cancer screening? • Now • At age 40 years • At age 45 years • At age 50 years

38. Question 7 • A 65-year-old woman underwent initial colonoscopy 1 month ago for colorectal cancer screening. A 6mm tubular adenoma of the sigmoid colon was found and removed. The patient has no family history of colorectal cancer. Which of the following is the most appropriate recommendation for colorectal cancer surveillance for this patient? • Repeat colonoscopy in 1 year • Repeat colonoscopy in 3 years • Repeat colonoscopy in 5 years • Flexible sigmoidoscopy in 5 years • Virtual colonoscopy (CT colonography) in 5 years

39. Question 8 • A 50-year-old man comes for an annual health maintenance visit. He feels well, and medical history is unremarkable. There is no family history of colorectal cancer. Physical examination and routine labs are normal. Which of the following is the most appropriate recommendation for colorectal cancer screening for this patient? • FOBT now, repeat every 2-3 years • Flex sig now, repeat every 2-3 years • Barium enema now, repeat every 2-3 years • Colonoscopy now, repeat every 10 years • Virtual colonoscopy now, repeat every 10 years

40. Question 9 • Three months ago, a 62-year-old man underwent segmental sigmoid colon resection for a near-obstructing colorectal cancer found of flex-sig. Surgery was considered curative, and the patient did not require post-op chemo or radiation. He has no family history of colorectal cancer or polyps. On follow-up exam today, he feels well. PE is normal. Which of the following is the most appropriate colorectal cancer surveillance procedure for this patient? • Colonoscopy now • Colonoscopy in 1 year • Colonoscopy in 3 years • CT scan of the abdomen now • CT scan of the abdomen in 3 years

41. Question 10 • A 67-year-old man undergoes diagnostic colonoscopy after he has a positive FOBT. A sigmoid colon CA is found. The remainer of the colonoscopic exam is normal. A CT of the abdomen shows no mets. CEA is slightly elevated. The patient undergoes resectino of the sigmoid with good results. Post-op recommendations include follow-up office visits every 3 months for 3 years, CEA measurement, and surveillance colonoscopy.

42. Question 10 Continued • When should the first surveillance colonoscopy be performed? • In 1 year • In 3 years • In 5 years • Only if CEA level increases