GASTROENTEROLOGY

1. GASTROENTEROLOGY Tests for Alcoholism

2. National Institute on Alcohol Abuse and Alcoholism (NIAAA) • Reports 20% of medical OPD consults are alcohol related and is considered ‘risky’ levels of consumption: • Men - 5 or more drinks a day or 15 or more a week • Women- 4 or more a day or 8 or more a week

3. ETOH: Major health risks • Liver disease • Heart Disease • Cancers- Liver, Pancreas, Lymphomas, Breast • Pancreatitis • Women: at greater risk- miscarriages/ fetal malformations, alcohol syndromes in babies- 40,000 babies a year

4. ?Assess • CAGE questionnaire- Did you Feel like- • Cut down consumption • Annoyed by others comments • Guilty about drinking • Eye-Opener in the morning

5. Lab Tests • GGT- • (Gamma-glutamyl transpeptidase, GGTP) • Higher the level the greater the “insult”- • liver disease • congestive heart failure • alcohol consumption and use of • drugs including- (NSAIDs), lipid-lowering drugs, antibiotics, histamine blockers, antifungal agents, seizure control medications, antidepressants, and hormones such as testosterone. • Oral contraceptives (birth control pills) and clofibrate can decrease GGT levels. • Smoking increases levels • Higher in Afro Americans

6. Normal Ileum

7. Celiac Disease: AKA- Gluten Enteropathy • An autoimmune disease characterized by an inappropriate immune response to dietary proteins found in wheat, rye, and barley • Dietary proteins- gluten and gliadin (Incidence- 1/133)(Only 3% diagnosed) • Causes symptoms associated with malnutrition and malabsorption. • An inherited tendency that is triggered by an environmental, emotional, or physical event • 5 to 15% of close family members also may be affected

8. Features of Malabsorption • Abdominal pain and distension • Anemia • Bleeding tendency • Bloody stool • Bone and joint pain • Changes in dental enamel • Diarrhea • Fatigue • Greasy foul-smelling stools • Oral ulceration • Weakness • Weight loss Food Allergies Infertility Dermatitis- itchy blisters Lymphomas

9. Best tests • anti-tissue transglutaminase antibody (anti-tTG), IgA • Anti-Gliadin Antibodies (AGA), IgG and IgA • Anti-Endomysial Antibodies (EMA), IgA (Very Specific) difficult to do test • Anti-Reticulin Antibodies (ARA), IgA (60% positive)

10. Other Useful Tests • CBC (complete blood count) to look for anemia • ESR (erythrocyte sedimentation rate) to evaluate inflammation • CRP (C-Reactive protein) to evaluate inflammation • CMP (comprehensive metabolic panel) to determine electrolyte, protein, and calcium levels, and to verify the status of the kidney and liver • Vitamin D, E, and B12 to measure vitamin deficiencies • Stool fat, to help evaluate malabsorption

11. What do they mean?

12. Cystic Fibrosis (CF) • Caused by mutations in a gene located on chromosome 7. (AR) • Production of a protein called cystic fibrosis transmembrane regulator (CFTR). • Caucasians and Ashkenazi Jews have the highest population carrier rates (about 1 in 20-25). • Absent or defective production and function of CFTR leads to abnormal electrolyte and water movement in and out of the epithelial cells

13. CF • interferes with electrolyte and fluid balances • sweat is up to five times saltier • Chronic cough and sputum production • Persistent chest infection • Weight loss and malnutrition (failure to thrive) • Pancreatitis • Chronic diarrhea and foul-smelling, greasy stools • Diabetes related to chronic pancreatitis • Delayed growth and delayed sexual development at puberty • Enlargement or rounding (clubbing) of the fingertips and toes • Chronic hepatic disease and biliary cirrhosis • Hypoproteinemia and edema • Male infertility (obstructive azoospermia)

14. CF Tests • Sweat Chloride. • Stool test for Trypsin/chymotrypsin • Fecal fat • Complete metabolic panel • Basic metabolic panel • Amylase • Lipase • Semen analysis • Sputum cultures

15. Tests for malnutrition • Lipids • CBC (Complete Blood Count) • CMP (Comprehensive Metabolic Panel) • Albumin • Total protein • For nutritional status and deficiencies: • Prealbumin (is decreased in malnutrition, rises and falls rapidly, and can be used to detect short-term response to treatment) • Iron tests (such as Iron, TIBC, and Ferritin) • Vitamin and minerals (such as B12 and Folate, Vitamin D, Vitamin K, Calcium, and Magnesium)

16. Inflammatory Bowel Diseases • affect about a million people in US • conditions vary in severity from patient to patient and change over time • periods of active disease may alternate with periods of remission. • ESR (erythrocyte sedimentation rate) to detect inflammation • CRP (C-reactive protein) to look for inflammation • CBC (complete blood count) to check for anemia

17. Diarrhea Investigations • Parasites: Giardia lamblia (giardia), Entamoeba histolytica (E. histolytica), and Cryptosporidium parvum (crypto). • Viruses: Rotavirus (children) Norwalk, noroviruses (also called Norwalk-like viruses), adenoviruses, calciviruses, cytomegalovirus (CMV), and HIV

18. Diarrhea Investigations • Bacteria: • Salmonella, often found in raw eggs, raw poultry and in pet reptiles • Shigella, from fecally-contaminated food and water • Campylobacter, from raw or undercooked poultry • Escherichia coli 0157:H7 (E. coli)- Spinach • Staphylococcus aureus and species of Yersinia and Vibrio • Clostridium difficile toxin

19. Diseases associated with Diarrhea • Inflammatory bowel conditions- IBD • Bowel dysfunction – IBS • Malabsorption disorders –cystic fibrosis • Stomach or gallbladder surgery • Food intolerance, such as lactose intolerance or celiac disease • Chemotherapy or abdominal or gastrointestinal radiation • Endocrine diseases- diabetes and thyroid disease • Self-induced with laxatives • Psychogenic causes such as stress

20. Malnutrition • Anemia • Weight loss, decreased muscle mass, and weakness • Dry scaly skin • Edema • Hair that has lost its pigment • Brittle and malformed (spooned) nails • Chronic diarrhea • Slow wound healing • Bone and joint pain • Growth retardation (in children) • Mental changes such as confusion and irritability • Goiter

21. ?Tests for Malnutrition • Lipids • CBC (Complete Blood Count) • CMP (Comprehensive Metabolic Panel) • Albumin • Total protein • For nutritional status and deficiencies: • Prealbumin (is decreased in malnutrition, rises and falls rapidly, and can be used to detect short-term response to treatment) • Iron tests (such as Iron, TIBC, and Ferritin) • Vitamin and minerals (such as B12 and Folate, Vitamin D, Vitamin K, Calcium, and Magnesium)

22. Metabolic Syndrome • 20% of adults (about 47 million) • Central/abdominal obesity as measured by waist circumference • [Men - Greater than 40 inches (102 cm); • Women - Greater than 35 inches (88 cm)] • Fasting triglycerides greater than or equal to 150 mg/dL (1.69 mmol/L) • HDL cholesterol [Men - Less than 40 mg/dL (1.04 mmol/L); Women - Less than 50 mg/ dL (1.29 mmol/L)] • Blood pressure greater than or equal to 130/85 mm Hg • Fasting glucose greater than or equal to 110 mg/dL (6.1 mmol/L)

23. Colon Related Tests • Colorectal Cancers- 11% of cancer deaths • Colorectal cancer frequently develops without early symptoms. • Symptoms that can occur include: • Diarrhea, constipation, or other changes in bowel habits lasting 10 days or more • Blood in the stool (either bright red or dark in color) • Unexplained anemia • Abdominal pain and tenderness in the lower abdomen • Abdominal discomfort (frequent gas pains, bloating, fullness, and cramps) • Intestinal obstruction • Weight loss with no known reason • Stools narrower than usual • Constant tiredness

24. Begin colorectal cancer screening when they turn 50 • First-degree relative has had colon cancer, for instance, screening should start 10 years prior to the age that relative was diagnosed • High fat and meat diets • minimal fruit, vegetable, and fiber intake. • Lifestyle factors: cigarette smoking, obesity, and a sedentary lifestyle.

25. Other risk factors for colon cancer • Personal or family history of colon cancer or polyps • ulcerative colitis, and • immunodeficiency disorders

26. Four common screening tests recommended

27. Pancreatic Cancer • 33,730 diagnosed /32,300 mortality • 4th leading cause of cancer death • No specific test exists • Comprehensive metabolic panel • CA 19-9 (Cancer Antigen 19-9): a tumor marker for pancreatic cancer; it may be used to monitor for cancer recurrence but is not useful for detection or diagnosis • CEA (Carcinoembryonic antigen): a tumor marker used as a monitoring tool • Other tests, such as fecal fat, stool trypsin, trypsinogen, amylase, and lipase help evaluate how well the pancreas is functioning and to determine whether pancreatic enzyme supplementation is necessary.

28. Other Pancreatic Conditions • Pancreatitis • Pancreatic insufficiency- related to pancreatitis/ cystic fibrosis • Tests- • Fecal fat • Trypsin (an enzyme that digests protein)

29. Pancreatitis • M>F, Alcohol related • Drugs such as valproic acid and estrogen • Viral infections such as mumps, Epstein-Barr, and hepatitis A and B • Hypertriglyceridemia, hyperparathyroidism, or hypercalcemia • Cystic fibrosis • Reye's syndrome in children • Pancreatic cancer • Surgery in the pancreas area (such as bile duct surgery) or trauma

30. Tests for Pancreatitis • Amylase (responsible for digesting carbohydrates) 2 to 12 hours after the beginning of symptoms and peaks at 12 to 72 hours. It may rise to 5 to 10 times the normal level and will usually return to normal within a week. • Lipase (digests fats) increases in the blood within 4 to 8 hours of the beginning of an acute attack and peaks at 24 hours.

31. CANCER MARKERS A PRIMER

32. The Pathologies and their tumor markers

33. Cancer Marker Panels

34. PROSTATE CANCER • PSA: an inflammation or trauma of the prostate (e.g. in cases of urinary retention, or following rectal examination, cystoscopy, colonoscopy, transurethral biopsy, laser treatment or ergometry) can lead to PSA elevations of varying • Free PSA: in patients receiving therapy, particularly hormone withdrawal therapy, the FPSA/PSA quotient cannot be utilized to differentiate prostate hyperplasia from cancer of the prostate.

35. b2M: BETA 2 MICROGLOBULIN • acute lymphblastic leukemia • chronic myelogenous leukemia • acute myeloid leukemia and multiple other leukemias • lymphoma • mulitple myeloma • prostate cancer • ovarian cancer • and renal cell carcinoma

36. IL6: Interleukin 6 • stimulates the growth and differentiation of human B-cells and is also a growth factor for plasmacytomas • elevated in breast cancer • renal cell cancer • ovarian cancer and • multiple myeloma

37. Interleukin-2 (IL-2) • hormone-like substance released by stimulated T lymphocytes • Used in treatment of metastatic renal cell carcinoma and metastatic myeloma (MM) • Lung cancer marker • Autism

38. Neuron Specific Enolase (NSE) • Elevated in lung cancer; non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) • It is also been associated with neuroblastomas, medullary thyroid carcinoma, Wilm’s tumor and pheochromocytoma

39. Ferritin • testicular cancer • neuroblastoma • Burkitt’s lymphoma • lung cancer • leukemia and • larynx cancer

40. Human Chorionic Gonadotropin-beta (hCG) • a tumor-associated antigen that is in various types of cancer. Most commonly, hCG beta is elevated, >10 mIU/ml in • gynecological cancers • colorectal • seminoma testicular • bladder • liver • stomach • pancreas • lung • brain and • kidney cancers

41. Tumor Marker • Carcinoembryonic Antigen (CEA) • CEA results to determine the stage and extent of disease and the outlook in patients with cancer, especially colorectal cancer. • CEA is also used as a marker for other forms of cancer-monitoring patients with cancer of the rectum, lung, breast, liver, pancreas, stomach, and ovary. • CEA test is not used for screening the general population.

42. Carcinoembryonic antigen (CEA) • Found in tumors of: • uterus • lung • breast • liver ,GI , colorectal, • kidney and • pancreas , and • typically among tobacco users . • One of the most useful applications of this marker is as a post surgical prognostic indicator in the treatment of neoplasms. • Any elevation of this marker after conventional treatment of neoplasms has been correlated with a recurrence of cancer .

43. A2m: alpha 2 macroglobulin • Decreasing levels of A2M have been observed in prostate cancer • Prostate Specific antigen can also bind to A2M and this complex can be used for prostate cancer • A2M levels lower than 500 ng/ml could be considered cancerous