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GASTROENTEROLOGY Tests for Alcoholism 1 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 2 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 3 ?Assess CAGE questionnaire- Did you Feel like- Cut down consumption Annoyed by others comments Guilty about drinking Eye-Opener in the morning 4 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 5 Normal Ileum 6 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 7 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 8 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) 9 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 10 What do they mean? Anti-tTG antibodies, IgA Total IgA Anti-tTG antibodies, IgG Anti-Gliadin antibodies (AGA), IgG Diagnosis + + - + - - Symptoms not likely due to celiac disease - - + + Possible celiac disease, false negative anti-tTG, IgA due to total IgA deficiency Presumptive celiac disease 11 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 12 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) 13 CF Tests Sweat Chloride. Stool test for Trypsin/chymotrypsin Fecal fat Complete metabolic panel Basic metabolic panel Amylase Lipase Semen analysis Sputum cultures 14 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) 15 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 16 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 17 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 18 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 19 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 20 ?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) 21 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) 22 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 23 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. 24 Other risk factors for colon cancer Personal or family history of colon cancer or polyps ulcerative colitis, and immunodeficiency disorders 25 Four common screening tests recommended Test Description Recommendation Pros Cons Fecal Occult Blood Test Test to detect hidden blood in stool sample Annually Inexpensive; easy to do Misses some cases; detects blood not due to cancer Sigmoidoscopy Examination of the rectum and lower colon with a rigid or flexible lighted instrument Every 5 years Simpler and less preparation than colonoscopy Misses some cases Double barium contrast enema Series of x-rays of the colon and rectum; patient is given an enema with a white, chalky solution that outlines the colon and rectum on the x-rays Every 5 to 10 years Does not require sedation Same preparation needed as for colonoscopy Colonoscopy Examination of the rectum and entire colon with a lighted instrument Every 10 years Perhaps most useful test Preparation and conscious sedation required; most invasive 26 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. 27 Other Pancreatic Conditions Pancreatitis Pancreatic insufficiency- related to pancreatitis/ cystic fibrosis TestsFecal fat Trypsin (an enzyme that digests protein) 28 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 29 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. 30 CANCER MARKERS A PRIMER 31 The Pathologies and their tumor markers Breast CA-15-3; CEA; CYFRA 21-1 Ovary CEA; CA 125; CA 19-9; AFP; BHCG Uterine SCC; CYFRA 21-1; CEA; CA 19-9; CA 125 Prostate PSA; FPSA and ratio Testicle BHCG; AFP Colorectal CEA; CA 19-9; CA 125 Pancreas CEA, CA 19-9; CA 72-4 Liver AFP; CEA Stomach CA 72-4; CEA; CA 19-9 Esophagus CEA; CYFRA 21-1 Thyroid CEA; NSE Lung NSE; CYFRA 21-1; CEA; CA 125; CA 19-9 Bladder TPA; CEA; CYFRA 21-1 32 Cancer Marker Panels The panel for women The panel for men CEA CEA CA 15-3 (BREAST CANCER) CA 19-9 CA 19-9 (OVARY/ UTERINE/ COLORECTAL/ CA 125 PANCREAS/ STOMACH/ LUNG CANCERS) CA 125 CA 72-4 CA 72-4 (STOMACH/ PANCREAS CANCERS) PSA + FPSA with ratio AFP (OVARY/ TESTTICLE/ LIVER CANCERS) AFP BHCG (germ cells, ovaries, bladder, pancreas, BHCG stomach, lungs and liver) b2M B2M NSE NSE CYFRA 21-19 BLADDER CANCER: CYFRA 21-1 LUNG CANCER: 33 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. 34 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 35 IL6: Interleukin 6 stimulates the growth and differentiation of human Bcells and is also a growth factor for plasmacytomas elevated in breast cancer renal cell cancer ovarian cancer and multiple myeloma 36 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 37 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 38 Ferritin testicular cancer neuroblastoma Burkitt’s lymphoma lung cancer leukemia and larynx cancer 39 Human Chorionic Gonadotropinbeta (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 40 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. 41 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 . 42 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 43