Gastric Outlet Obstruction due to Carcinoma of the Stomach - Model Answer (10 Marks)

a) Diagnosis

• 75-year-old male (age and sex favour gastric carcinoma - incidence increases with age, male predominance)
• Non-bilious vomiting of food taken 12 hours earlier = retained gastric contents, confirming obstruction at the pyloric/antral level (food has not reached the bile duct junction)
• Visible peristalsis moving LEFT to RIGHT = stomach trying to overcome the obstruction (classic finding)
• Epigastric lump (3 x 4 cm) = the tumour itself or involved lymph nodes
• Succussion splash = >200-300 mL stagnant fluid in the stomach after 3+ hours fasting, confirming gastric stasis
• Anorexia + significant weight loss over 4 months = features of malignancy
• 6 months duration with no prior history of peptic ulcer disease = malignant GOO is more likely (Bailey and Love states: "With the decreasing incidence of peptic ulceration, gastric outlet obstruction should be considered malignant until proven otherwise")

b) Aetiology of Gastric Carcinoma (Causes of GOO and of Gastric Cancer)

• Helicobacter pylori infection - the most important environmental factor; principally associated with carcinoma of the body and distal stomach (not proximal); causes chronic gastritis → intestinal metaplasia → dysplasia → carcinoma (Correa's cascade)
• Pernicious anaemia and gastric atrophy - increased risk due to achlorhydria and mucosal changes

• High salt diet (salted, smoked, and pickled foods)
• High intake of N-nitroso compounds (processed meats)
• Deficiency of antioxidants (vitamins C and E)
• Low intake of fresh fruits and vegetables
• Environmental evidence: incidence falls among Japanese migrants living in the USA, confirming the role of diet

• Gastric adenomatous polyps
• Gastric atrophy / chronic atrophic gastritis
• Intestinal metaplasia
• Post-surgical stomach (Billroth II gastrectomy, gastroenterostomy, pyloroplasty) - approximately 4x risk; thought to be due to bile reflux and intestinal metaplasia

• Cigarette smoking
• Alcohol consumption
• Obesity (particularly for proximal gastric cancer / GEJ adenocarcinoma)
• Industrial dust ingestion

• Familial diffuse gastric cancer: CDH1 (E-cadherin) gene mutation
• Hereditary syndromes: FAP, Lynch syndrome, BRCA1/2 mutations
• TCGA molecular subtypes: EBV-positive, microsatellite unstable (MSI), genomically stable (GS), chromosomal instability (CIN)
• Mutations in TP53, ARID1A, RHOA, SMARCA1, CDH1, Wnt pathway

• Male sex (men more commonly affected)
• Age > 50-60 years
• Higher incidence in Eastern Europe, Japan, China, and Latin America
• Lower socioeconomic status (for distal gastric cancer)

c) Investigations

Routine/Blood Tests:

• Full blood count (FBC): anaemia (iron deficiency from chronic blood loss, or normocytic from malignancy)
• Serum electrolytes, urea, creatinine: hypochloraemic, hypokalaemic metabolic alkalosis (from prolonged vomiting of hydrochloric acid) - note: less severe than in benign peptic GOO due to relative hypochlorhydria in gastric cancer
• Liver function tests (LFTs): assess for hepatic metastases and general nutritional status
• Serum albumin/prealbumin: nutritional assessment
• Coagulation profile
• Tumour markers: CEA, CA 19-9, CA 72-4 (limited sensitivity but useful for monitoring treatment response and recurrence)

Specific Investigations:

• Directly visualises the tumour, its location, size, and degree of obstruction
• Allows multiple biopsies (minimum 6-8 biopsies) for histopathological confirmation
• Endoscopic biopsy is essential to exclude malignancy (Bailey and Love)
• Assessment of gastric emptying and pyloric patency

• Classic "rat-tail" or "shouldering" deformity at pylorus/antrum
• Shows the site and extent of narrowing
• Demonstrates gastric dilatation and delayed emptying
• Useful when endoscopy is not tolerated

• Gold standard for staging (T, N, M assessment)
• Identifies local tumour extension, lymphadenopathy, liver metastases, peritoneal seeding, ascites
• Assesses resectability

• Best modality for T-stage (depth of tumour invasion into gastric wall layers) and N-stage (perigastric lymph nodes)
• Guides treatment decisions (resectable vs neoadjuvant chemotherapy first)

• Mandatory before planned curative resection in most centres
• Detects peritoneal metastases not visible on CT (upstages ~25-30% of patients)
• Peritoneal washings for cytology - positive cytology = M1 disease

• Useful in selected cases to detect distant occult metastases
• Less useful in signet ring / mucinous type tumours (FDG-avid)

• Pulmonary metastases, mediastinal involvement

• Quick assessment for liver metastases, ascites, lymphadenopathy

d) Management

Step 1: Resuscitation and Pre-operative Optimisation

• IV fluid resuscitation with isotonic saline (0.9% NaCl) + potassium supplementation to correct hypochloraemic hypokalaemic metabolic alkalosis
• Replacing sodium chloride and water allows the kidney to correct the acid-base abnormality
• Nasogastric (NGT) / orogastric tube insertion to decompress and empty the stomach (a wide-bore tube or orogastric lavage may be needed to clear retained food)
• Nutritional support: enteral/parenteral nutrition pre-operatively if severely malnourished
• DVT prophylaxis: low molecular weight heparin + compression stockings (due to Trousseau's sign of malignancy-associated thrombosis)
• Correction of anaemia if necessary (transfusion or iron supplementation)
• Optimisation of comorbidities (especially in a 75-year-old patient - cardiac, pulmonary, renal assessment)

Step 2: Staging and Assessment of Resectability

• CT chest/abdomen/pelvis + EUS + staging laparoscopy as above
• Multidisciplinary team (MDT) discussion

Step 3: Definitive Treatment

A) Curative Intent (Resectable Disease - ~20-30% at presentation)

• Distal/antral carcinoma: Subtotal gastrectomy (Billroth II / Roux-en-Y reconstruction) with D2 lymphadenectomy
• Body/total stomach: Total gastrectomy with Roux-en-Y oesophagojejunostomy + D2 lymphadenectomy
• Surgical objectives: R0 resection (clear margins) with removal of at least 15 lymph nodes for adequate staging
• In elderly/frail patients with advanced local disease: palliative procedures for GOO relief may be preferred

• The FLOT regimen (5-FU/folinic acid, oxaliplatin, docetaxel) is currently standard in fit patients - given before and after surgery
• Improves survival compared to surgery alone (FLOT4 trial)
• Alternatively: CAPOX (capecitabine + oxaliplatin) perioperatively

• Combined chemoradiotherapy post-surgery in selected patients (particularly if R1 resection or inadequate lymphadenectomy)

B) Palliative Management (Unresectable or Metastatic Disease - ~70-80% at presentation)

• Endoscopic self-expanding metal stent (SEMS) insertion across the pylorus/duodenum - first-line palliation for GOO; technically easier, faster recovery
• Surgical gastrojejunostomy (bypass) - for patients with longer expected survival or failed stenting; provides good palliation of GOO
• Surgical palliative resection (R2) - considered only in selected cases for symptom control

• Platinum-based combination regimens (e.g., FOLFOX, CAPOX, or FLOT)
• Trastuzumab added if HER2-positive tumour (test all gastric cancers for HER2)
• Ramucirumab (anti-VEGFR2) for second-line treatment
• Immune checkpoint inhibitors: nivolumab, pembrolizumab (especially in PD-L1-positive or MSI-high tumours)

• Nasogastric/NJ tube feeding
• Parenteral nutrition where enteral feeding is not possible

• WHO analgesic ladder; coeliac plexus block for refractory pain

• Palliative care team involvement, symptom control, psychological support

Summary Box

• Bailey and Love's Short Practice of Surgery 28th Edition, pp. 1190-1194
• Current Surgical Therapy 14e

Unconjugated Neonatal Hyperbilirubinemia - Model Answer

PART 1: Causes and Management of Unconjugated Neonatal Hyperbilirubinemia (5 Marks)

Definition

• Total serum bilirubin (TSB) > 5 mg/dL within the first 24 hours = always pathological
• TSB > 20-25 mg/dL = risk of bilirubin-induced neurologic dysfunction (BIND)

Causes of Unconjugated Neonatal Hyperbilirubinemia

A) Physiological (Most Common)

• Immature hepatic conjugation (low UGT1A1 enzyme activity)
• Increased RBC breakdown (fetal haemoglobin replaced by adult haemoglobin)
• Increased enterohepatic circulation
• Appears day 2-3, peaks day 3-5, resolves by 2 weeks (term) / 3 weeks (preterm)
• Bilirubin typically peaks at ~6 mg/dL but may reach up to 12 mg/dL in term infants

• Exact pathophysiology uncertain; may be hormonally mediated or due to increased enterohepatic resorption of bilirubin
• Peaks later (day 10-21), may persist 3-10 weeks
• Characterised by mild unconjugated hyperbilirubinemia

B) Pathological

• Crigler-Najjar syndrome Type I (complete absence of UGT1A1) and Type II (partial absence)
• Gilbert syndrome (benign, mild reduction)
• Hypothyroidism (congenital)
• Prematurity (immature liver enzymes)

• Drugs (competitive inhibition)
• Sepsis / fasting

• Delayed passage of meconium (Hirschsprung disease, meconium ileus, intestinal atresia)
• Pyloric stenosis
• Dehydration / poor feeding
• Breast milk jaundice

• Galactosaemia
• Dehydration (poor weight gain, poor feeding)

Management of Unconjugated Neonatal Hyperbilirubinemia

General / Supportive Measures:

• Encourage feeding (breast or bottle) - oral intake stimulates enterohepatic circulation, reduces bilirubin reabsorption; increases hepatic blood flow and conjugation
• Treat the underlying cause (infection, hypothyroidism, haemolysis)
• Ensure adequate hydration
• Transcutaneous bilirubin monitoring or total serum bilirubin (TSB) measurement to assess risk using AAP nomogram (Bhutani curves)
• Identify risk factors (prematurity, haemolysis, G6PD deficiency, previous sibling with jaundice)

Specific Treatment:

• Intravenous immunoglobulin (IVIG): For isoimmune haemolytic jaundice (ABO/Rh incompatibility) - reduces haemolysis and rate of bilirubin rise; reduces need for exchange transfusion
• Tin-mesoporphyrin: Inhibits haem oxygenase (blocks bilirubin production) - used in select centres; not routine
• Phenobarbitone (pre-natal to mother or post-natal to neonate): Induces UGT1A1 enzyme activity; rarely used in modern practice

PART 2: Exchange Transfusion - Role, Indications, and Procedure (5 Marks)

Definition

Role of Exchange Transfusion

1. Rapidly reduces serum bilirubin - the most effective method to bring down dangerously high bilirubin levels quickly
2. Removes sensitised (antibody-coated) RBCs - in Rh/ABO incompatibility, prevents further haemolysis
3. Removes maternal antibodies (IgG) - reduces ongoing haemolysis
4. Corrects anaemia - especially in severe erythroblastosis fetalis
5. Removes toxic metabolites and inflammatory mediators in sepsis
6. Approximately 85-90% of circulating bilirubin is removed with a double-volume exchange transfusion

Indications for Exchange Transfusion

• TSB at exchange transfusion threshold level on AAP nomogram (age-specific, risk-stratified)
• TSB continues to rise or remains above exchange levels despite intensive phototherapy
• Signs of acute bilirubin encephalopathy (ABE) regardless of bilirubin level: high-pitched cry, opisthotonos, seizures, apnoea, retrocollis
• TSB > 25 mg/dL in term neonate (widely used threshold in many centres)

• TSB rising at >0.5 mg/dL/hour despite phototherapy
• Cord bilirubin > 4.5 mg/dL AND cord haemoglobin < 11 g/dL (in Rh haemolytic disease)
• Hydrops fetalis with haemoglobin < 7 g/dL at birth (often requires intrauterine transfusion first)
• Severe anaemia with cardiac failure

• Lower thresholds apply (exchange at lower TSB values due to immature blood-brain barrier)

Procedure (Double-Volume Exchange Transfusion)

• Volume: 2 x blood volume = 2 x 80 mL/kg = 160-170 mL/kg (replaces ~85% of neonatal RBCs)
• Blood used: Fresh (< 5-7 days old), CMV-negative, irradiated, O-negative or cross-matched packed RBCs reconstituted with FFP (ratio ~2:1, haematocrit ~50%)
• Route: Umbilical venous catheter (preferred) or umbilical arterial catheter; in older infants, peripheral venous + arterial
• Technique: Isovolumetric push-pull technique - small aliquots (5-20 mL) removed and replaced alternately
• Continuous monitoring: heart rate, oxygen saturation, temperature, blood glucose
• Post-procedure: monitor for rebound hyperbilirubinemia; continue phototherapy

Complications of Exchange Transfusion

PART 3: Phototherapy - Mechanism and Complications (5 Marks)

Definition

Mechanism of Phototherapy

• Native bilirubin exists as the 4Z,15Z (Z,Z) isomer - lipid-soluble, cannot be excreted without conjugation
• Light (wavelength 460-490 nm, blue-green spectrum; optimal peak ~478 nm) converts Z,Z bilirubin to the 4Z,15E (Z,E) and 4E,15Z configurational isomers
• These isomers are more polar (less lipophilic) and can be excreted in bile WITHOUT conjugation
• This reaction is reversible in the gut (reverts back to Z,Z), hence enterohepatic reabsorption occurs - a limitation of phototherapy

• Sustained phototherapy converts Z,Z bilirubin to lumirubin (a structural isomer - cyclobilirubin)
• Lumirubin is irreversible, water-soluble, and excreted in bile AND urine without conjugation
• This is the dominant mechanism in intensive phototherapy

• Light oxidises bilirubin to colourless, water-soluble oxidation products (biliverdin, monopyrroles, dipyrroles)
• Excreted in urine
• Slowest mechanism

• Wavelength: 460-490 nm (blue-green light); LED lights preferred (narrow spectrum, low heat)
• Irradiance: ≥30 µW/cm²/nm for intensive phototherapy
• Distance: 20-30 cm from infant
• Surface area exposed: Maximum (naked infant, eye shield and gonad cover)
• Fibre-optic blankets ("bili-blankets") provide phototherapy from below simultaneously

Complications of Phototherapy

Quick Reference Summary

• Rosen's Emergency Medicine, p. 3226-3228
• Tietz Textbook of Laboratory Medicine 7th Edition, pp. 867-871
• Guyton and Hall Medical Physiology, pp. 1054
• Creasy & Resnik's Maternal-Fetal Medicine