logging in or signing up GUT Hormones with an overview of GI NET venkatalekharaju Download Post to : URL : Related Presentations : Let's Connect Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 135 Category: Others/ Misc License: All Rights Reserved Like it (0) Dislike it (0) Added: November 11, 2012 This Presentation is Public Favorites: 0 Presentation Description Overview of Noncarcinoid GI NETs Comments Posting comment... Premium member Presentation Transcript GUT Hormones with an overview of GI NET with a focus on Gastrinoma: GUT Hormones with an overview of GI NET with a focus on Gastrinoma GUT Hormones with an overview of GI NET with a focus on Gastrinoma Venkata Lekharaju ( Pawan ) SPR GASTROENTEROLOGY 09/11/2012Overview: Overview NETs GEP NETs CASE SCENARIO GASTRINOMA HYPERGASTRINEMIA GUT HORMONESNET (definition): NET (definition) Neuroendocrine neoplasms , defined as epithelial neoplasms with predominant neuroendocrine differentiation, arise in most organs of the bodySynonyms to define NET: Synonyms to define NETPowerPoint Presentation: GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ( NONCARCINOID )GEP NET: GEP NET Neuroendocrine tumors comprise approximately 2% of all malignant tumors of the gastrointestinal system Incidence of all noncarcinoid NETs is approximately one half that of all carcinoids Noncarcinoid NETs have been reported to occur in 0.4–1.5/100,000 of the populationEpidemiology: EpidemiologyBasic biology of NET: Basic biology of NET 14 endocrine cell types in the gut Produce at least 33 hormones and biogenic aminesTypes of NET: Types of NET The cell type-specific hormonal substance produced by the enteroendocrine cell defines the type of NETs originating from that cell Serotonin- carcinoid , Gastrin-gastrinoma , Vasoactive intestinal peptide- VIPoma , Insulin- insulinoma , Glucagon- glucagonomaGenetics: Genetics MEN type 1 Von- Hippel Lindau disease Neurofibromatosis type 1Useful tips (if you can remember): Useful tips (if you can remember) 57% of MEN type 1 has ZES 20% of ZES patients have MEN type 1 30% of all GFRomas are associated with MEN 1 4-5% of Insulinomas are associated with MEN 1 80% of MEN 1 develop PET No PETs are associated with MEN PETs occur in 12-17% of patients with VHL NF 1 is associated with duodenal somatostatinomasEnteroendocrine tumor syndromes other than Carcinoid: Enteroendocrine tumor syndromes other than CarcinoidInsulinoma: Insulinoma Syndrome: Insulinoma Hormone: Insulin, Proinsulin Clinical features: Hypoglycaemia, wt loss Site: >95% pancreas Malignant: >10% Treatment: Surgery, Diet, IV dextrose, chemotherapy, Diazoxide , SSTAVIPOMA: VIPOMA Syndrome: Verner -Morrison pancreatic cholera WDHA Hormone: VIP Clinical features: Secretory diarrhoea, hypokalemia , achlorhydria , metabolic acidosis, flushing, wt. loss Site: 90% pancreas Malignant: >50% Treatment: Surgery, IV fluids, chemotherapy, SSTAGlucagonoma: Glucagonoma Syndrome: Glucagonoma syndrome Hormone: Glucagon Clinical features: Hyperglycaemia, necrolytic migratory erythema , DVT, depression Site: >90% pancreas Malignant: >50% Treatment: Surgery, Diet, Insulin, chemotherapy, SSTASomatostatinoma: Somatostatinoma Syndrome: Somatostatinoma syndrome Hormone: Somatostatin Clinical features: Diabetes, gallstones, wtloss , steatorrhea Site: Pancreas Malignant: 70-80% Treatment: Surgery, Insulin, pancreatic enzymesExtremely rare: Extremely rareExtremely rare: Extremely rare Tumor Syndrome Hormone Features Site Malignant Treatment ACTHoma Ectopic Cushing’s syndorme ACTH HTN, DM Pancreas Lung >99% Surgery Chemo SSTA PTHrPoma Hyper parathyroidism PTHrP Hyper calcaemia Renal stones Pancreas >99% Surgery Chemo Neurotensinoma ? N eurotensin ? Pancreas Lung ? Surgery Chemo Calcitoninoma ? Calcitonin ? Pancreas Lung >80% Surgery Chemo GRFoma Acromegaly GHRF Acromegaly Pancreas Lung Thymus 30% Surgery SSTANonspecific markers: Nonspecific markers Chromogranin A Chromogranin B Pancreastatin Pancreatic polypeptide Neuron specific enolase Alpha and beta subunits of chorionic gonadotropin 5 HIAA (24hr Urine) (diet and meds)Imaging: Imaging Imaging is indicated at different stages in the patient’s care 1. Screening of at-risk populations 2. Primary lesion detection 3. Assessing extent of disease 4. Follow-up and assessing response to treatment.Imaging: Imaging US EUS CT MRISensitivities: SensitivitiesGold standard: Gold standard SRS ( Somatostatin receptor scintigraphy ) 68 Ga DOTATOC PET Octreoscan = 111 In-DTPAOC SPECT Density of receptors (type 2 and 5) determines the result and not the tumor size Functionality of the tumor is not relevant Not useful if you are suspecting InsulinomaOctreoscan: Octreoscan Confirms the diagnosis and localizes a NET, Imaging metastases or staging, Monitoring progression or regression of tumors , Predicts response to cold somatostatin analog treatment (the more strongly positive SRS, the greater the likelihood of a favorable response to this treatment), and Predicts the likelihood of a favorable response to a therapeutic dose of radiolabeled somatostatin analog (peptide-receptor radionuclide therapy). A negative SRS in the presence of a progressing tumor could indicate more strongly the need for aggressive surgery and/or chemotherapyLimitations: Limitations Reduced sensitivity in smaller (sub-centimetre) lesions and in lesions exhibiting low receptor density; 2-day imaging protocol; and potential interference by co- adminstration of therapeutic somatostatin analoguesHistology: Histology Mitotic rate Microscopic necrosisGrading system: Grading systemPrognosis: PrognosisGASTRINOMA: GASTRINOMANew GP referral in a Gastro clinic: New GP referral in a Gastro clinic A 65-year-old woman Abdominal discomfort has been present intermittently for the past year and is described as burning epigastric pain that improves with meals and increases with fasting. Upper endoscopy performed 6 months ago revealed a duodenal ulcer and duodenitis . Antral biopsy specimens were negative for Helicobacter pylori . Treatment was initiated with a proton pump inhibitor (PPI) but her symptoms persisted. PPI= Omeprazole 20mg BDCase continues: Case continues Past medical history is notable for hypertension and coronary artery disease. Medications include a PPI, thiazide diuretic, β-blocker, angiotensin -converting enzyme inhibitor, low-dose aspirin, and a statin . She denies using over-the-counter medications.Case continues: Case continues Physical examination shows normal vital signs, and mild tenderness to palpation of the epigastrium . Hemoglobin level is 13 g/ dL with a normal white blood cell and platelet count. Serum creatinine , alkaline phosphatase , and aspartate aminotransferase levels are normal.What will you do?: What will you do? Repeat endoscopy? A repeat endoscopy revealed duodenal erosions with healing of the previously observed duodenal ulcer. Repeat antral biopsy specimens were negative for H pylori and duodenal biopsy procedures performed during the second endoscopy revealed a slight increase in neutrophils without evidence of neoplasm or infection.Clever SPR: Clever SPR Checks fasting Gastrin level Fasting gastrin is 310ng/L (SI units) Normal is <100ng/LWhat should be the approach to this patient with documented peptic ulcer disease and elevated fasting gastrin level?: What should be the approach to this patient with documented peptic ulcer disease and elevated fasting gastrin level?Peptic ulcer disease: Peptic ulcer disease Protective factors Aggressive factors Mucous Mucosal blood flow Growth factors Prostaglandins Acid Pepsin H.pylori NSAIDS What is refractory ulcer?Causes of refractory ulcer: Causes of refractory ulcer Ischaemia , Lymphoma, Crohn’s disease, Amyloidosis , Sarcoidosis , Systemic mastocytosis , Drugs/toxins ( bisphosphonates , potassium chloride, mycophenolate mofetil , and clopidogrel ), Eosinophilic gastroenteritis Infection (cytomegalovirus, herpes simplex virus, tuberculosis, and syphilis)When to suspect Gastrinoma: When to suspect Gastrinoma Ulcers in unusual locations (second part of the duodenum and beyond), Ulcers refractory to standard medical therapy, Ulcer recurrence after acid-reducing surgery, Ulcers presenting with frank complications (bleeding, obstruction, and perforation)Hypergastrinemia: Hypergastrinemia Gastric hypochlorhydria or achlorhydria ( eg , pernicious anemia ); Retained gastric antrum after gastric surgery; H pylori infection; Gastric outlet obstruction; Renal insufficiency; Small-bowel obstruction; and Conditions such as rheumatoid arthritis, vitiligo , diabetes mellitus, and pheochromocytomaHypergastrinemia: Hypergastrinemia PPI H2 receptor blockersZollinger Ellison Syndrome: Zollinger Ellison Syndrome Peptic ulcer Severe ulcerative oesophagitis DiarrhoeaEpidemiology: Epidemiology Accurate incidence not known Very rare 0.1 to 1% of patients with peptic ulcer disease M>F Age group 30-50 years Diagnosis usually delayed (4-6 years) More than 50% have liver mets at the time of diagnosisSite: Site 70% occur in the duodenum Less often malignant Tend to be small May be multipleTypes: Types Sporadic Familial Common Solitary More malignant More common site is pancreas Rare Multiple SmallerMEN type 1: MEN type 1 Autosomal -dominant disorder that involves primarily 3 organ sites Parathyroid glands (80%–90%), Pancreas (40%–80%), and Pituitary gland (30%–60%). Obtaining a thorough family history is important when considering multiple endocrine neoplasia type I.Clinical predictors of poor survival: Clinical predictors of poor survival Liver mets Diffuse extent Bone mets Size >3cm Cushings syndrome Female sex Absence of MEN 1 Markedly raised serum gastrinDiagnostic tests: Diagnostic tests Fasting hypergastrinemia Basal acid output (BAO) is greater than 10 mEq /h. Secretin stimulation testTreatment: Treatment Role of surgery is controversial More useful in MEN 1 association Usually is Whipples PPI SST Analogues 5FU based regimensGUT Hormones: GUT HormonesPowerPoint Presentation: Hormone/peptide neurocrine endocrine paracrine VIP + Substance P + Neuropeptide + Somotostatin + + + Cholecystokinin + + Gastrin + Secretin + GIP + Motilin + + Neurotensin ? + + Guanylin + +Summation of GUT hormones: Summation of GUT hormonesPowerPoint Presentation: Hormone Source Target Action Cholecystokinin I cell in duo, jeju, neurons in ileum, colon Pancreas gallbladder ↑ enz secretion ↑ contraction GIP K cell in duo, jeuju pancreas ↓ fluid absorp ↑ insulin release Gastrin G cell in antrum, duo Parietal cell ↑ aci d secretion ↑ motility GRP Vagus nerve G cell Gastrin r eleasePowerPoint Presentation: Hormone Source Target Action Glucagon Alpha cell in pancreatic islet liver ↑ glycogenolysis ↑ gluconeogenesis Guanylin Ileum, colon Small and large intestine ↑ fluid secretion Motilin EC cell, Mo cell in upper GI tract Eso sphincter Stomach, duo Smooth muscle contraction Neurote nsin Neurons, ECC in ileum Intestinal smooth muscle ↓ GI motility ↑ blood flowPowerPoint Presentation: Hormone Source Target Action Peptide YY L cell in ileum, colon Stomach Pancrease ↓ vagal mediated acid secretion ↓ enz and fluid secretion Secretin S cell in small intestine Pancrease Stomach ↑ HCO3 and fluid secretion by pancreatic ducts ↓ gastric a secretion Somatostatin D cell in stomach , duodenum, pancreatic islet Stomach Intestine Pancrease Liver ↓ gastrin release ↑fluid absorption ↑ smm contraction ↓ endo /exocrine secretion ↓ bile flowPowerPoint Presentation: Hormone Source Target Action Substance P Enteric neurons Intestine Pancrease ↑ GI motility ↓ HCO3 secretion VIP ENS neurons Small intestine Pancrease smm contraction ↑SB secretion ↑pancreatic secretionPowerPoint Presentation: THANK YOU You do not have the permission to view this presentation. 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