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UPPER BLEEDING GIT AND ITS CAUSES Factors predictive of UBGIT35 APPROACH TO BLEEDING UPPER GIT - Patient-reported history of melena (LR:...

UPPER BLEEDING GIT AND ITS CAUSES Factors predictive of UBGIT35 APPROACH TO BLEEDING UPPER GIT - Patient-reported history of melena (LR: 5.1-5.9) - Melenic stool on examination (LR: 25) CAUSES - Blood or coffee grounds detected during NG lavage (LR: 9.6) Variceal Bleed - Ratio of BUN to Serum Cr > 30 (LR: 7.5) 1. Gastro-oesophageal varices (30%) *Note: the presence of blood clots in the stool made an UBGIT less likely (LR: 0.05) Non-variceal Bleed 2. Peptic ulcer disease (bleeding peptic ulcer) (50%) Melena 3. Gastritis, gastric erosions, duodenitis - Passage of altered blood (black tarry stool) that originate proximal to the ligament of 4. Mallory-Weiss tear (10%) Treitz (90%) – types of melena: 5. Gastric malignancy (10%) (a) Fresh melena – jet black with sheen, tarry, non-particulate, almost liquid in 6. Dieulafoy lesion – large tortuous arteriole (aneurysm) in the upper part of the stomach consistency (suggest fairly acute bleeding) 7. Aorto-enteric fistula (5%) (b) Stale melena – black-grey, dull, mixed with normal stool, occasionally particulate Others (suggest bleed which stopped followed with melena) 8. Bleeding from other sources: Haemoptysis, nasopharyngeal bleeding - Ddx: Iron stool – greenish hue on rubbing between gloved fingers, particulate - If gloved finger is stirred in a cup of water, melena will “dissolve” completely with no HISTORY (if patient is stable) sedimentation and turn the water black, but iron stool will sedimentate and turn the water green 1. Nature of bleeding (confirm hematemesis and rule out haemoptysis) Haemoptysis Frank PR bleeding - Bloody expectoration from the larynx, trachea, bronchi and the lungs - Very brisk upper GI bleed can present as frank PR bleeding as blood passes down so fast it - Patient will describe a feeling of something in their throat followed with the abrupt doesn’t get altered (severe bleeding) expectoration of blood (frothy and bright red) Note: spectrum from coffee-ground vomitus  melena (stale / fresh)  hematemesis  UBGIT Hematemesis (red blood or coffee-ground emesis) masquerading as PR bleed - Vomiting of blood from upper GIT (proximal to the ligament of Treitz, at D-J junction) - The vomited blood might be mixed with food particles 2. Determine Etiology (variceal vs. non-variceal bleed) - The colour of the vomitus depends on the contact time with the HCl acid of the stomach - Any previous variceal bleed  ask patient whether he/she goes for regular banding or OGD (red  brown) screening and banding - Coffee grounds vomitus is altered blood (due to gastric acid) and can come from gastric - Any history of chronic liver disease  ask for risk factors (i.e. alcohol ingestion, hepatitis ulcer, gastritis/erosions, or variceal blood that has entered the stomach (suggest limited B/C, any regular follow-up for liver disease – AFP, U/S HBS) bleeding) - Can be fresh red blood as in variceal bleeding, Mallory-Weiss tear, AV malformation (suggest moderate to severe bleeding) Hematemesis Haemoptysis Not associated with cough Associated with Cough Not Frothy Frothy Darker Red (altered by gastric acid) Bright Red (aerated) Melena Present Melena Absent 35 JAMA. 2012 Mar;307(10):1072-9. 61 3. Aetiological clues (differentiating causes of non-variceal bleed) PHYSICAL EXAMINATION Peptic Ulcer Disease (most common cause) 1. Vital Signs (most important) - History of dyspepsia, previous H. pylori infections, previous OGD done - Assess hemodynamic stability and postural BP - Drug History – NSAIDs, antiplatelets, steroids, anticoagulants, TCM - Any resting tachycardia - Secondary to cirrhosis-induced hypergastrinemia from decreased hepatic metabolism of GI hormones 2. Confirm UBGIT - DRE for melenic stool (differentiate from Fe-laden stools) Stress Ulcer 3. Determine Etiology - Curling ulcer – large acute ulcer in the duodenum (cx from burns) - Variceal Bleed  stigmata of chronic liver disease, jaundice - Cushing’s ulcer – gastric ulcer produced by elevated ICP - Non-variceal bleed o H&N: Bleeding source in nose or mouth, cervical lymph nodes, Mallory-Weiss tear o Abd: Tenderness, guarding, rebound, epigastric mass, arterial bruit of AAA - It is a diagnosis of exclusion o Rectal: PR bleed, anal, perianal or rectal pathology - Secondary to violent retching following alcoholic binge  lead to longitudinal tear below 4. Look for complications the GE junction leading to haematemesis - Signs of Anemia  Face – (i) conjunctival pallor (ii) pallor of mucus membrane Dieulafoy’s Disease – AVM of the gastric fundus  Cardiac Auscultation – short systolic flow murmur at aortic area - Presents with massive or recurrent bleeding coming from an area of apparently normal  Pulse – (i) tachycardia (ii) bounding (iii) collapsing pulse gastric mucosa  characterized by a large tortuous arteriole in the submucosal that bleeds  Hands – pallor of palmar creases - More common in males, with multiple co-morbids (i.e. HTN, IHD, CRF, DM) - Lungs  examine for aspiration pneumonia - Exclude Peritonism - Suspect in bleeding with no history of alcohol abuse or NSAIDs use Malignancy (gastric carcinoma) - Early  asymptomatic, epigastric pain, dyspepsia - Intermediate  anemia, melena, hematemesis, early satiety, dysphagia, nausea/vomiting, bloatedness - Late  loss of appetite, loss of weight, obstructive jaundice (mets to liver) 4. Amount of blood - If patient is having haematemesis, ask how much blood  Cup? Bowl? - Hematemesis: easily 1.5L of blood in stomach before vomiting out (bleeding more than pylorus can empty) 5. Complications - Symptomatic anemia  SOB on exertion, dizziness, syncope, chest pain, palpitation, lethargy/fatigue - Gauge percentage of blood loss  15-30%  class 2 – Narrowed Pulse Pressure, Resting Tachycardia, Postural Hypotension  30-40%  class 3 – Supine Hypotension, marked tachypnoea, confused, anxious  > 40%  class 4 – Minimal urine output, markedly depressed or lethargic - AMI  esp. if it’s an old patient with previous history of IHD 6. Comorbidities - Makes patient more susceptible to hypoxemia  Elderly patient (>60), IHD, COPD - Predispose to fluid overload during resuscitation  IHD/CCF, CRF 62 IMMEDIATE MANAGEMENT - IV resuscitation Whatever the cause, the patient should first be resuscitated and then investigated urgently to  1L N/S run fast (i.e. over 15min) – caution in patients with renal & heart failure determine the cause of bleeding  inform GS registrar on call of the patient’s admission  Reassess patient response: o (1) Responder  sustained improvement clinically & biochemically 1. Resuscitation o (2) Transient responder - ABC o (3) Non-responder  Assess if patient can respond logically  good cerebral perfusion, otherwise aim to  Transient Responder  KIV colloids (gelofusine / haemaccel) + wait for GXM protect airway  Non-responder Management  KIV colloids, E-bloods and adjunct monitoring (CVP line)  Patient may still be in early stage (class 1) hypovolemic shock  manage pre-emptively  aim to stabilise patient for transfer to scope room for emergency scope in the setting 1. Nasal Prongs (supplemental O2 to increase O2 carrying capacity which is of acute bleed determined by Hb concentration and O2 saturation) o Restrictive transfusion strategy to keep Hb > 7g/dL (showed improved outcomes as 2. IV cannula  2 large bore 18G catheter inserted into the veins at the antecubital compared to liberal transfusion strategy [transfusion when Hb < 9] in patients fossa with acute UBGIT) 36 Note other structures present: (from medial to lateral)  median nerve, brachial artery, bicep brachii tendon, o May consider platelets if patient is on antiplatelet meds (qualitative defect in radial nerve) – Mother Buys 10 Rabbits platelets - even if plt is normal, they are dysfunctional) IV Cannula Sizes: 14G – orange, 16G – grey, 18G, green, 20G, pink, 22G, Blue, 24G – yellow o FFP if patient is on anticoagulants or PT/PTT prolonged ( + vitamin K)  Bloods for investigation 2. Adjuncts 1. GXM: order in active bleed 4 pints PCT - NG tube if patient is having haematemesis – prevents aspiration, allows gastric lavage prior 2. FBC (Hb will not drop in first 24hrs, thrombocytopenia  secondary to to OGD (DO NOT insert if suspect varices) hypersplenism in portal hypertension – can exacerbate bleeding, MCV and MCHC - Catheterisation – monitor I/O balance esp. in elderly or when large amount of fluid  determine cause of anemia) resuscitation required, or anticipating surgery 3. U/E/Cr (dehydration  raised Ur more than Cr (isolated uraemia suggestive of - Intubate if: 1) massive uncontrolled active hematemesis bleeding GIT), Metabolic Disturbances  hypokalemic, hypochloremic, metabolic 2) signs of decompensation e.g. obtunded alkalosis with paradoxical aciduria* 4. PT/PTT (r/o coagulopathy which can exacerbate bleeding) 3. Early medications 5. LFT (Child's score - ind etiology and outcome) – do in alcoholic hx or liver disease - IV omeprazole 80mg bolus  8mg/hr infusion X 3/7 6. ABG, Lactate   stomach pH and stabilises clot formation  regimen to prevent re-bleed (normal Tx dose 40mg bd)  Other Investigations - If suspecting varices – IV somatostatin/octreotide, IV antibiotics 7. ECG and cardiac enzymes to detect any AMI (STEMI) - Withhold all antiplatelets, anticoagulants, NSAIDS 8. CXR: r/o perforation, aspiration 4. Close monitoring *With vomiting  K+, Cl-, Na+ and H2O is loss from the body  Intravascular hypovolemia sensed by JGA and leads to the activation of the RAAS  body reabsorb Na+ and H2O via kidney (Na+/K+ ATPase) and excrete K+  - Monitor for: SHOCK ( HR,  BP,  urine output,  confusion & lethargy) But since K+ is critical in maintaining cardiac membrane stabilization  body attempts to conserve K+ by - Keep NBM and patient’s parameter monitored hourly paradoxically increasing excretion of H+ (alkalosis also leads to a lowering of the circulating ionized calcium, and tetany can occur) - If patient is in Class II shock – do monitoring  I/O charting – insert an IDC to measure urine o/p (aim: 0.5ml/kg/hr)  CVP monitoring  For massive UBGIT where patient presents with hypotension, can insert NG tube and aspirate to confirm suspicious (do not insert in suspect varices) 36 N Engl J Med 2013; 368:2341 63 5. Emergency oesophagogastroduodenoscopy(OGD) DIAGNOSTIC STUDIES38 Alternatively, scope the next available OGD (usually following day) - 3 Indications: 1. Shock / hemodynamic instability (ensure BP is stable before OGD – requires sedation) 2. Active BGIT (esp. hematemesis, also fresh melena) 3. Suspected variceal bleed - Not just low Hb as emergency scope causes more stress - GXM bloods and transfused as clinically indicated - Role of endoscopy  (i) diagnosticate, (ii) therapeutic, (iii) prognosticate - Confirm UBGIT & identify source of bleeding, - Biopsy of gastric mucosa (+ CLO test* if ulcer) – All gastric ulcers should be biopsied (6 bites) – risk of underlying malignancy & would require f/u scope in 6 weeks to document ulcer healing Diagnostic *Biopsy rapid urease testing (CLOtest = Campylobacter-Like Organism)  test ability of H. pylori to secrete urease enzyme which cleaves urea to liberate ammonia and bicarbonate (↑pH)  colour change from Yellow (-ve) to Red (+ve) - Varices: (i) Band ligation/sclerotherapy, (ii) glue Therapeutic - Non-variceal: (i) HaemoClip, (ii)Injection of adrenaline (1:10,000), (iii) Argon Plasma Coagulation (heater probe) Prognostic - Endoscopic stigmata of recent haemorrhage – forest classification (see PUD) - After endoscopic treatment  patient is to receive 80mg bolus IV PPI followed by continuous infusion of 8mg / hr of IV PPI for 72 hours (thereafter revert to oral PPI)  reduce rate of recurrent bleeding, shortened length of hospitalization, decreased need for endoscopic retreatment and blood transfusion37 - Contraindications: Perforation – air insufflation during OGD will cause  abdominal compartment syndrome  decrease venous return  patient may DIE  splinting of the diaphragm - Risk of OGD  Anaesthetic Risk 1. Risk of Sedation – respiratory depression secondary to airway compromise 2. CVS risk – AMI, CVA  Procedural-Related Risk 1. Bleeding and Perforation (1 in 10,000) 2. Failure of endoscopic haemostasis 3. Failure of complete scope – standard OGD scope to D2 (ligament of Treitz) 37 38 N Engl J Med 2000; 343:310-316 Pocket Medicine 4th Edition: Gastrointestinal Bleeding – Section 3-3 64 SUBSEQEUNT MANAGEMENT 1. Risk Stratification  Rockall Score (see below) or Blatchford Scoring System 1. Age of Patient History 2. Major Co-Morbid  IHD, CCF, Renal / Liver Failure Physical Examination 1. Shock – Tachycardia or Hypotension 1. Stigmata of recent haemorrhage OGD findings 2. Diagnosis  Mallory-Weiss or Malignancy or Others 2. Correct Risk Factors - H. Pylori Infection  PPI (Omeprazole) 20mg + Clarithromycin 500mg + Amoxicillin 1000mg / Metronidazole 400mg BD x 1/52 then Omeprazole 20mg BD x6/52  followed by test of cure - H. Pylori Negative  PO PPI - NSAIDs induced gastric bleed  choose alternatives (i.e. COX-2 inhibitors or add PPI cover) 3. Management of Re-bleeding - Repeat OGD and re-attempt endoscopic haemostasis - If failure of endoscopic haemostasis  Surgery  normally have 2 goals: curative and decrease acid component, but mortality and morbidity risk is high so better to keep surgery short thus rather than decreasing acid component, patient is placed on life-long PPI  Radiological Intervention  CT mesenteric angiogram OR mesenteric angiogram KIV embolization 1. CT: non-invasive, require contrast (risk of nephropathy) 2. Mesenteric Angiogram: catheterize through femoral vein (risk of puncture), require contrast, if negative can be due to low blood flow rate  KIV prop up BP but risk of further bleed (clinical judgment call) Blatchford Scoring System: only clinical and laboratory factors, no endoscopic component AIMS 65 Scoring System: prognosticate inpatient mortality rates Albumin 1.5 2 points = 3% mortality Altered Mental States (GCS < 14) 3 points = 9% mortality Systolic BP 65 5 points = 25% mortality 65 PORTAL HYPERTENSION Hepatic venous pressure gradient (HVPG) ≥ 6mmHg (normal = 1-5mmHg)  Portal HTN ≥ 10mmHg – high risk of gastroesophageal varices developing  Portal HTN ≥ 12mmHg – high risk of variceal bleed and development of ascites Normal portal flow rate is about 1-1.5L/min ANATOMY - Portal veins drain blood for the small intestines, large intestines, stomach, spleen, pancreas and gallbladder. - The SMV and the splenic vein unite behind the neck of the pancreas to form the portal vein - The portal trunk divides into 2 lobar veins  Right branch drains the cystic vein  Left branch drains the umbilical and paraumbilical vein (caput medusa in portal HTN) - The left gastric (coronary) vein with runs along the lesser curvature of the stomach receives distal oesophageal veins (oesophageal varices in portal HTN) PATHOPHYSIOLOGY Portal Hypertension: chronic increase in portal pressure due to mechanical obstruction of the portal venous system. It is almost an unavoidable consequence of cirrhosis and responsible for many complications of CLD (see below) Cirrhosis (1) architecture distortion (nodules compression sinusoids & active intra-hepatic vasoconstriction [↓NO])  increase in resistance to portal blood flow  formation of porto- systemic collaterals (2) high arterial pressure (splanchnic arteriolar vasodilatation) on low pressure venous system & insufficient portal decompression through collaterals (higher resistance) increased portal blood flow (hyperdynamic circulation) Ohm’s Law is V = IR | Poiseuille’s Law R=8hL/pr4  this can be applied to vascular flow where P = FR or P = F8hl/pr4  decrease portal vascular radius produce a dramatic increase in portal vascular resistance ↑portal pressure gradient (P) = ↑in resistance to portal flow (R) (intrahepatic & collateral) and ↑in portal blood inflow (F) 66 CAUSES OF PORTAL HYPERTENSION Pre-hepatic Heptaic Post-hepatic Massive Splenomegaly CIRRHOSIS Severe right-sided HF with consequent ↑ in splenic vein (most commonly due to alcohol Constrictive Pericarditis blood flow and/or hepatitis B/C) Massive Fatty Change Hepatic vein thrombosis Hemochromatosis Portal vein thrombosis (Budd Chiari Syndrome*) Wilson’s Disease Schistosomiasis IVC thrombosis Caroli Disease Congenital Atresia Congenital IVC malformation Congenital Hepatic Fibrosis * Gives rise to ascites, hepatomegaly and pain, commonly caused by thrombophilic disorder – treatment: shunting or liver transplantation & long term anticoagulation INVESTIGATIONS - Ultrasound (Liver & Spleen) – radiological findings:  Dilated splenic and superior mesenteric veins ≥ 11mm  Splenomegaly > 12cm  Reduction in portal flow mean velocity serum [Br]  ruptured GB or perforated DU CLINICAL PRESENTATION  cell count and differential (FEME)  albumin – to determine SAAG - Progressive abdominal distension ± painless or abdominal discomfort  total protein concentration - a/w weight gain, SOB, early satiety, and dyspnoea  amylase concentration (pancreatic ascites or bowel perforation) - Fever, abdominal tenderness, and AMS  suspect SBP  Microbiology – gram stain smear, culture (aerobic / anaerobic), cytology  Others – LDH / TG / Glucose / TB culture / Br / proBNP PHYSICAL EXAMINATION  Examine to confirm diagnosis TREATMENT o Abdominal distension  Conservative o Low salt diet – 2000mg / day or 88mol/day o Flank dullness  shifting dullness (pathognomonic)  fluid thrill o Fluid restriction – only if serum sodium 500cells/mm3)  IV ceftriaxone or oral quinolones (i.e. ciprofloxacin) CLASSIFICATION o Avoid or use with caution in patients with cirrhosis – propranolol / ACEi / ARBs / NSAIDs SAAG ≥ 1.1g/dL SAAG 94% - Establish 2 or more large bore peripheral IV lines - Monitoring  Vitals, ECG, pulse oximeter, urine output (IDC) - Labs  GXM (4units), FBC, U/E/Cr, PT/PTT, ±LFT, ±Cardiac Enzymes - Infuse fluids  1 litre N/S fast and reassess parameters - ICU bed and facilities should be made available Note: DO NOT insert NG tube if oesophageal varies is suspected  worsen variceal bleed Note: Under-resuscitate in variceal bleed as blood volume expansion increases portal venous pressure in patients with cirrhosis which may sustain active bleed or precipitate further bleeding  initiate blood transfusion if Hb 6units transfusion Obstruction (evaluate nature of obstruction)  endoscopic hydrostatic balloon dilation  surgical  Failure of endoscopic haemostasis (BLOCK) therapy (indications)  Repeated episodes of bleeding after initial stabilization (up to 2 attempts at  Persistent obstruction after 7 days of non-operative management obtaining endoscopic haemostasis)  Recurrent obstruction  Shock a/w recurrent haemorrhage  Antrectomy (include ulcer) with Billroth 1 or 2 reconstruction  Continued slow bleed with transfusion requirement ≥ 3 units / day - PUD may erode through entire thickness of gastric / duodenal wall into adjacent  Duodenotomy and 3 point ligation  Biopsy followed by oversewing the Penetration abdominal organs (i.e. pancreas, bile ducts, liver, small / large intestines) (oversewing/under-running) bleeding vessels or wedge excision of (BURROW) - Px: acute onset of pancreatitis, cholangitis, diarrhoea of undigested food  Post-operative H. Pylori eradication the ulcer - Surgery not recommended * Bleeding DU usually located at posterior Complications of Massive Blood Transfusion duodenal wall within 2cm of the pylorus 1 Fluid overload and acute pulmonary edema typically erode into gastroduodenal artery Transfusion Related Acute Lung Injury (TRALI) Immune related Acute Febrile Haemolytic Reaction 2 complications Non-haemolytic febrile transfusion risk Allergic Reaction / Anaphylaxis Infection related Bacterial Infection 3 complications Viral Infection – Hep B (1 in 205,000), Hep C (1 in 1.8 million), HIV (1 in 1.9 million) Hyperkalaemia Citrate Toxicity Metabolic 4 Dilution of clotting factors  bleeding problems Complications Thrombocytopenia Hypocalcaemia 5 Hypothermia * most common cause of febrile reaction post-transfusion = febrile non-hemolytic transfusion reaction (FNHTR) – caused by antibodies directed against donor leukocytes and HLA antigens 51 N Engl J Med 2000; 343:310-316 52 Ann Intern Med. 2009 Apr 7;150(7):455-64 53 Gastrointest Endosc. 2011 May;73(5):900-8 76 ANATOMY OF THE STOMACH (BLOOD SUPPLY AND LYMPHATIC DRAINAGE) Left & Right Esophageal Cystic Hepatic Branches Left Gastric Short Gastric Artery (supply fundus) Hepatic Celiac trunk (T12) Common Hepatic Splenic Artery Gastroduodenal Right Gastric Left Artery Gastroepiploic Artery Superior Pancreatico- Right duodenal Gastroepiploic (ant. & post.) Artery 77 GASTRIC CANCER RISK FACTORS – MULTIFACTORIAL (INFECTION, ENVIRONMENT, GENETICS) (Divide RF into Major and Minor Risk Factors – major includes: H. pylori and Diet) EPIDEMIOLOGY54 - 7th most common cancer in males and 8th most common in females in Singapore 1. Infection – Helicobacter Pylori - 4th leading cause of cancer related mortality in males and 5th in females in Singapore - Ask patient about past infection, whether he has been on triple therapy before, about - Ethnic: Gastric Cancer more common among Chinese > Indian > Malays previous endoscopic procedures and its results - Gender: Gastric Cancer more common in Males > Females - Lead to chronic gastritis (intestinal metaplasia as a precursor lesion) - ASR of Gastric Cancer: 11.8 / 100,000 in Males and 7.0/ 100,000 in Females - 2x increased risk of developing gastric cancer - Lifetime risk for stomach cancer in Chinese Males: 1 in 50 - Large geographical variation – increase prevalence across Asia (Korea  Japan  China) and 2. Environmental Eastern Europe - Diet: preserved foods (nitrosamines – canned food), smoked foods (high salt), - Overall incidence slowly decreasing but sharp increase in cancer of the gastric cardia / GE - Smoking: 2x increased risk of gastric cancer (intestinal cancer of distal stomach) junction in western countries (related to increased incidence of GERD) - Low socioeconomic status: poor refrigeration of food and diet a/w increased risk - Aspirin, Fresh Fruits & Vegetables, Selenium & Vitamin C  protective factors BORRMANN’S CLASSIFICATION 3. Genetic - Family History: 1.5x increased risk in siblings / offspring of patients with gastric CA - Blood Group A - Hereditary (familial) diffuse gastric cancer: linked to germline mutation of e-cadherin (CDH 1)  early onset, highly penetrant, diffuse gastric carcinoma  Prophylactic Gastrectomy has been performed on carriers of truncating germline CDH1 mutations  Common among New Zealanders, Autosomal Dominance syndrome 4. Significant Past Medical History - Previous Gastric Resection (i.e. Partial Gastrectomy) – allow reflux of bile induces chronic gastritis – significant if surgery > 7 years ago - Barrett Oesophagus – increased risk of gastroesophageal junctional tumour How to describe OGD findings of GOO - Fungating/excavating/ulcerative tumour with contact bleeding in antrum and occluding it - Previous diagnosis of gastric polyps (adenomatous / inflammatory) - (i) Presence of food debris and (ii) absence of duodenal visualization implicates inability to - Chronic Atrophic Gastritis  Menetrier’s Disease (hyperplastic hypersecretory gastropathy) intubate past the pylorus - Consonant with GOO secondary to distal gastric carcinoma (likely Borrmann type X)  Pernicious Anemia – risk of gastric cancer in the long term - Proceed with a bx for histo confirmation and prognostication by Lauren’s Classification Type 4 – Linitis Plastica - Poorly differentiated - Diffuse involvement ± signet ring cells - Usually in younger, female patients, late presentation (malignant ascites) with poor prognosis 54 Trends in Cancer Incidence in Singapore 2008-2012 (data report are as of 7th June 2013) 78 HISTOLOGICAL TYPES PRESENTATION Early to Intermediate Intermediate to Late Late Adenocarcinomas (95%) - Asymptomatic - Loss of appetite - Anemia^, Melena, - Non-specific Epigastric Pain - Loss of weight - From mucous producing cells in the gastric mucosa / Dyspepsia Hematemesis - (see above – spread) - Early Satiety and dysphagia - Lauren classification (divide into 2 main sub-types or mixed): (require high index of (cardia tumour) (a) Intestinal (expanding) type – papillary, tubular, mucinous suspicious, early presentation - Nausea, Vomiting and intervention = better  Occur in elderly males and in the distal stomach (more likely to cause GOO) prognosis) (obstruction  dysphagia,  Precursor lesion of intestinal metaplasia and dysplasia (as in chronic gastritis) epigastric fullness, bloatedness)  Haematogenous spread to distal organs History Any previous OGD? (in Japan – * non-metastatic effects OGD is a screening tool) (1) thrombophlebitis / migratory (b) Diffuse (infiltrative) type – signet ring cell, undifferentiated If present with pyloric tumour, phlebitis (Trousseau Syndrome)  a/w invasive growth pattern and rapid submucosal spread  linitis plastica presentation is like GOO Gastric anti-secretory agents and (2) DVT are due to effects  Occur in younger patients, females and in the proximal stomach will improve symptoms and ^Fe Deficiency Anemia 2o to of the tumour on thrombotic may mask Gastric CA– disease and haemostatic mechanisms  Transmural and Lymphatic spread with early metastases are more common tumour bleed – low ferritin, should first be excluded (new (3) Seborrheic keratosis and  Worse overall prognosis low serum Fe, high transferrin, onset dyspepsia at age > 35 freckles (Leser-Trelat sign) high TIBC should cause concern) Signet Ring Cells: large cytoplasmic mucin vacuoles and - Melena - Cachexia - Asymptomatic PE - Palpable Epigastric Mass - Non-metastatic effects* peripherally displaced crescent shaped nuclei - Slight Epigastric Tenderness - Succussion Splash - Metastatic Effects Involves CDH1 mutation (encodes E-cadherin) which is also seen in SPREAD lobular carcinomas of the breast (some of which have signet ring - Local Spread (direct extension to neighbouring organs) – i.e. gastric antrum cancer spread cells too) (a) Pancreas (b) Transverse colon (c) Duodenum Non-adenocarcinoma (5%) - Lymphatic Spread Gastric Neuroendocrine Gastric Lymphoma (B-cell lymphomas Gastrointestinal Stromal (a) Local lymphatic spread to peri-gastric lymph nodes  further spread follow the arterial Types Tumours (carcinoids) – extra-nodal MALT type) Tumour (GIST)** supply (i.e. nodes along the branches of the celiac artery: left gastric artery, common Enterochromaffin-like Derived hepatic artery and splenic artery)  further spread to para-aortic nodes (ECL) cells in gastric Lymphocytes in gastric mucosa Interstitial cells of Cajal From (b) Enlarged Left Supraclavicular nodes (Virchow’s node) mucosa c-KIT (gain of function - Haematogenous Spread (via venous circulation) Hypergastrinemia H. Pylori chronic gastritis, Trisomy 3 mutation), PDGFRA (platelet (a) Hepatosplenomegaly with ascites and jaundice (liver) Etiology (i.e. Zollinger-Ellison and t(11;18) translocation derived growth factor (b) Rarely: Bony Tenderness (bone), Neurological Deficits (brain), Lungs (usually these organs syndrome, MEN type 1) receptor α gene mutation) are not worked up for metastasis) Carcinoid Syndrome – MALT = mucosal associated lymphoid c-KIT positive tumours treat - Trans-coelomic Spread (Peritoneal Seeding) Remarks a/w metastatic disease* tissue with imatinib (TKI) (a) Seeding to the omentum, parietal peritoneum  Peritoneal Carcinomatosis (can lead to small bowel obstruction which is hard to treat owing to multiple sites of involvement) *”Carcinoid syndrome: due to release of vasoactive substances into systemic circulation; characterized by cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhoea, right-sided cardiac valvular fibrosis (note: carcinoids confined to the GIT (b) Infiltration of the umbilicus (Sister Mary Joseph’s node) typically do not cause carcinoid syndrome as vasoactive substances produce undergo ‘first-pass’ effect in liver, hence carcinoid (c) Enlarged ovaries on PE (Krukenberg’s tumour) syndrome is strongly associated with metastatic disease)” (d) Fullness in pelvic cul-de-sac (Blumer’s shelf = shelf-like tumour of ant rectal wall, rectal mass ddx tuberculous peritonitis ** Mesenchymal Tumours of the GIT  leiomyomas / leiomyosarcoma, neurofibroma & GIST. GIST – ¾ are benign with indicators of malignancy including (1) size > 10cm, (2) mitotic index >5/10hpf & (3) site (extra-gastric position) – many are found incidentally but may present as vague abdominal pain (mass effect), GI bleed (necrosis of overlying mucosa), early satiety, LOW (obstructive COMPLICATIONS symptoms) - Bleeding  Fe deficiency anemia, melena, hematemesis - Gastric outlet obstruction  vomiting, dehydration, biochemical abnormalities (hypokalemic, hypochloremic metabolic alkalosis), aspiration ± pneumonia)  risk of aspiration pneumonia - Malnutrition  cachexia - Perforation 79 INVESTIGATIONS STAGING (TMN)55 - Allow direct visualization and multiple biopsies of suspicious - Tumour arising at the esophagogastric (EG) junction, or arising in the stomach 5cm or less from lesions (biopsy the edges of the ulcers) the EG junction and cross the EG junction  staged as oesophageal carcinoma (TNM system) - Screening examination (routinely done in Japan) – in US - Gastric cancer TNM staging  for distal stomach tumours and for tumours arising in the OGD + Biopsy Establish the population, warranted for high risk individuals: >20 years post- proximal 5cm but not crossing the EG junction Diagnosis partial gastrectomy, patients with pernicious anemia or atrophic gastritis, positive familial history T0 No evidence of primary tumour Double contrast upper GI barium contrast (limited diagnostic value) – except for linitis Tis Carcinoma in situ: intraepithelial tumour w/o invasion of the lamina propria plastica (↓distensibility, “leather-flask” appearance more obvious) T1 Tumour invades (a) lamina propria, muscularis mucosae, or (b) submucosa - Most significant prognostic factor is depth of tumour invasion T2 Tumour invades muscularis propria - 3 classifications (Boorman – based on macroscopic appearance of tumour, Lauren – T Tumour penetrates subserosa connective tissue – include those extending into gastrocolic or T3 divides tumour to intestinal or diffuse types and TMN – reflects depth of tumour gastrohepatic ligaments, or into greater or lesser omentum infiltration, nodal involvement and present of distant mets) Tumour invades (a) serosa (visceral peritoneum) or (b) adjacent structures (i.e. spleen, transverse T4 colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, SI and retroperitoneum) - Superior to CT in delineating depth of tumour invasion (gold N0 No regional LN metastasis Staging Endoscopic standard for T staging) and identifying perigastric N1 Metastasis in 1-2 regional LN Investigations Ultrasound lymphadenopathy (N staging accuracy = 70%) N N2 Metastasis in 3-6 regional LN - Addition of FNA for suspicious node increases accuracy to ~100% N3 Metastasis in 7 or more regional LN (divide to local & - Abdominal/Pelvis: Assess for haematogenous spread to distant Mo No Metastatic spread to distant organs M systemic staging) organ (i.e. most commonly liver mets), detect metastatic disease M1 Distant Metastasis or Positive Peritoneal Cytology Computer in the form of malignant ascites Tomography (CT) (1st test to do is to - CT Thorax (for gastric cardia tumour) T N M Stage 0 Tis 0 0 exclude mets) - Limited accuracy in determining nodal involvement Stage 1A 1 0 0 Positron emission - Combines spatial resolution of CT with contrast resolution of PET 2 0 0 Stage 1B tomography (PET) - Superior to CT scan alone 1 1 0 - Routine use of laparoscopy has been shown to detect small 3 0 0 Laparoscopic Stage 2A 2 1 0 volume peritoneal and liver mets in 20-30% of patients believed 1 2 0 Staging to have local-regional disease (upstage) 4a 0 0 FBC - Assess Hb levels Stage 2B 3 1 0 Supportive 2 2 0 U/E/Cr - Biochemical abnormalities a/w gastric outlet obstruction 1 3 0 Investigation to - Albumin as a marker of nutritional status (< 35 is poor,