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Summary of the Last 3 Answers

25. Graft vs Host Reaction

• Definition and Billingham's criteria (3 prerequisites)
• Pathophysiology - afferent sensitization + efferent effector phases
• Acute GvHD - classic skin/gut/liver triad, Glucksberg grading I-IV
• Chronic GvHD - scleroderma-like features, bronchiolitis obliterans
• Prevention - HLA matching, T-cell depletion, post-transplant cyclophosphamide
• Treatment - methylprednisolone first-line; ruxolitinib (JAK inhibitor) for steroid-refractory; ibrutinib and belumosudil for chronic GvHD
• Surgical relevance - TA-GvHD prevention by irradiating blood products

26. Hemangioma

• Infantile hemangioma - GLUT-1 positive, natural history (proliferate → involute), PHACES complications
• Treatment - oral propranolol as first-line; topical timolol; PDL laser; surgery
• Hepatic cavernous hemangioma - most common benign liver tumor; "cotton wool" CT enhancement; T2 "light bulb sign" on MRI; biopsy contraindicated
• Management - mostly conservative; enucleation preferred over resection for giant symptomatic lesions; TAE/RFA alternatives

27. Role of Colour Doppler in Surgery

• Principles - BART colour convention, RI/PI indices
• Peripheral arterial disease - carotid stenosis, PAD, AAA, graft surveillance
• DVT - non-compressibility criterion, varicose vein mapping pre-EVLT/RFA
• Hepatic/portal - portal hypertension, Budd-Chiari, liver transplant HAT monitoring
• Thyroid/parathyroid - Graves' "inferno" pattern, parathyroid adenoma "vascular pedicle" sign
• Scrotal - testicular torsion (absent flow = emergency), varicocele
• Intraoperative - free flap perforator marking, anastomosis patency
• Advances - CEUS, 3D Doppler, AI-assisted analysis

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25. GRAFT VERSUS HOST REACTION (GvHR) / GRAFT VERSUS HOST DISEASE (GvHD)

Definition

Prerequisites - Billingham's Criteria (1966)

1. The graft must contain immunologically competent cells (donor T-lymphocytes)
2. The recipient must be immunologically incompetent or tolerant - unable to reject the graft
3. There must be antigenic disparity (HLA mismatch) between donor and recipient

Incidence and Clinical Settings

• Allogeneic bone marrow / hematopoietic stem cell transplantation (HSCT) - most common and most important setting; incidence 30-70% depending on HLA match
• Solid organ transplants containing significant lymphoid tissue - liver, small bowel, lung transplants
• Blood transfusions in immunocompromised patients - Transfusion-Associated GvHD (TA-GvHD); nearly 100% fatal
• Maternal-fetal lymphocyte transfer - rare
• Frequency increases with degree of HLA mismatch and age of recipient

Pathophysiology

Phase 1 - Afferent Phase (Sensitization / Conditioning Injury)

• Pre-transplant conditioning (high-dose chemotherapy + total body irradiation) damages host intestinal mucosa and other tissues
• Massive release of pro-inflammatory cytokines: TNF-α, IL-1, IL-6, IFN-γ - the "cytokine storm" or "cytokine tsunami"
• This creates an inflammatory microenvironment that upregulates host MHC expression
• Donor antigen-presenting cells (APCs) and host APCs present alloantigens to donor T-cells
• Major histocompatibility complex (MHC/HLA) mismatch drives recognition

Phase 2 - Efferent Phase (Effector / Tissue Damage)

• Activated donor CD4+ helper T-cells (recognizing host MHC class II) coordinate the response
• CD8+ cytotoxic T-lymphocytes (recognizing host MHC class I) directly kill host cells via perforin-granzyme pathway and Fas-FasL interaction
• Natural killer (NK) cells amplify tissue injury
• Macrophages release reactive oxygen species and nitric oxide
• Further waves of cytokines (IFN-γ, TNF-α, IL-2) perpetuate a vicious cycle of inflammation and tissue destruction
• Target organs: Skin, gastrointestinal tract, liver (primary targets in acute GvHD)

Classification

A. Acute GvHD (aGvHD)

• Occurs within 100 days of transplant (classically within 30-60 days)
• Can occasionally occur as late-onset acute GvHD (beyond day 100)
• Classic triad of Skin + Gut + Liver involvement

Grading System - Glucksberg (Seattle) Criteria

Clinical Features - Acute GvHD

• Erythematous maculopapular rash beginning on palms, soles, ears, and nape of neck
• Spreads centripetally to involve trunk and face
• Severe: Confluent erythroderma, bullae, skin desquamation resembling toxic epidermal necrolysis
• Pruritus and burning sensation

• Upper GI: Nausea, vomiting, anorexia, dyspepsia (stomach/duodenum involved)
• Lower GI: Profuse, watery, secretory diarrhoea - hallmark; may be bloody in severe disease
• Crampy abdominal pain, distension, ileus
• Volume losses can be massive (>10 litres/day in severe cases)
• Risk of intestinal perforation in Grade IV

• Cholestatic jaundice (predominant)
• Elevated alkaline phosphatase, GGT, and bilirubin
• Hepatomegaly and right upper quadrant pain
• Severe: liver failure, coagulopathy, encephalopathy

B. Chronic GvHD (cGvHD)

• Occurs after 100 days post-transplant (or de novo, or as evolution from acute GvHD)
• Resembles a multi-organ autoimmune disorder
• Affects more organs than acute GvHD

NIH Grading of Chronic GvHD

Clinical Features - Chronic GvHD

• Early: lichenoid papules (resembles lichen planus)
• Late: sclerotic changes - thickened, tight skin resembling systemic scleroderma
• Poikiloderma (pigmentary changes), alopecia, nail dystrophy, loss of skin appendages

• Xerostomia (dry mouth), lichenoid plaques on buccal mucosa
• Painful erosions and ulcers
• Restriction of mouth opening in sclerotic disease

• Keratoconjunctivitis sicca - dry, gritty, painful eyes
• Photophobia, excessive tearing, corneal ulceration

• Bronchiolitis obliterans (BO) - progressive, irreversible obstructive airway disease
• FEV1/FVC <0.7 on PFTs, air trapping on HRCT
• Can lead to respiratory failure; major cause of non-relapse mortality

• Cholestatic pattern - elevated ALP, GGT, bilirubin
• Resembles primary biliary cirrhosis histologically

• Oesophageal webs/strictures causing dysphagia
• Malabsorption, weight loss, exocrine pancreatic insufficiency

• Myositis, polymyositis-like syndrome
• Joint contractures, fascial fibrosis

• Vaginal sclerosis and stenosis in females (significant morbidity)
• Urethral stricture in males

• Cytopaenias - thrombocytopaenia is a poor prognostic indicator
• Hypogammaglobulinaemia - recurrent bacterial infections

Diagnosis

Acute GvHD

• Primarily clinical - based on timing, organ involvement, and compatible history
• Skin biopsy:
  • Vacuolar/hydropic degeneration of basal keratinocytes
  • Apoptotic (dyskeratotic) keratinocytes - satellite cell necrosis
  • Perivascular and periappendageal lymphocytic infiltrate
  • In severe: full-thickness necrosis, subepidermal bullae
• Rectal/intestinal biopsy:
  • Crypt cell apoptosis (most characteristic finding)
  • Crypt dropout, mucosal ulceration in severe disease
  • Lymphocytic infiltrate in lamina propria
• Liver biopsy:
  • Lymphocytic infiltration and damage of small bile ducts (ductopenia)
  • Endotheliitis (lymphocytes beneath vascular endothelium)
  • Cholestasis

Differential Diagnoses to Exclude:

• Engraftment syndrome
• Drug-induced rash/hepatotoxicity/diarrhoea
• Viral infections: CMV enteritis/hepatitis, adenovirus, norovirus
• Clostridium difficile colitis
• Veno-occlusive disease (hepatic sinusoidal obstruction syndrome)
• Idiopathic pneumonia syndrome

Prevention Strategies

1. HLA Matching

• Best prevention is optimal HLA matching - match at HLA-A, B, C, DRB1, DQB1 (10/10 allele matching)
• Matched related donor (MRD) - lowest GvHD risk
• Matched unrelated donor (MUD) - higher risk; 10/10 match preferred
• Haploidentical (half-matched) - highest risk; requires special GvHD prophylaxis

2. T-Cell Depletion

• Ex vivo T-cell depletion of graft using anti-CD3/CD6 monoclonal antibodies or positive CD34+ selection
• In vivo T-cell depletion:
  • Anti-thymocyte globulin (ATG) - horse or rabbit derived
  • Alemtuzumab (anti-CD52)
• Reduces GvHD significantly but increases risk of: graft failure, delayed immune reconstitution, opportunistic infections, and disease relapse (loss of graft-versus-leukaemia effect)

3. Pharmacological Prophylaxis

• Cyclosporine A + short-course methotrexate (MTX days +1, +3, +6, +11) - classic Storb regimen
• Alternatively: Tacrolimus + methotrexate (preferred in many centres - lower aGvHD rate)

• Cyclophosphamide 50 mg/kg on days +3 and +4 post-transplant
• Selectively eliminates alloreactive T-cells (which have undergone rapid proliferation and are most sensitive)
• Spares regulatory T-cells and non-alloreactive cells
• Now standard of care for haploidentical transplants
• Increasingly used for matched transplants too
• Combined with tacrolimus + MMF from day +5

• Mycophenolate mofetil (MMF)
• Sirolimus (mTOR inhibitor)
• Abatacept (CTLA4-Ig - co-stimulation blockade)

Management / Treatment

Acute GvHD Treatment

• Methylprednisolone 1-2 mg/kg/day IV - cornerstone of treatment
• Continue background calcineurin inhibitor (cyclosporine or tacrolimus)
• Maintain therapeutic drug levels
• Overall response rate approximately 50%
• Grade I: topical steroids alone may suffice

• Ruxolitinib (Jakafi) - JAK1/2 inhibitor; FDA approved 2019 for steroid-refractory aGvHD in adults and children ≥12 years; overall response rate ~62%; now the preferred second-line agent
• Extracorporeal photopheresis (ECP) - especially for skin GvHD
• Infliximab (anti-TNF-α monoclonal antibody) - for gut GvHD
• Mycophenolate mofetil
• Sirolimus (mTOR inhibitor)
• Basiliximab (IL-2 receptor antagonist)
• Mesenchymal stromal cells (MSCs) - especially in paediatric GvHD

• Strict infection prophylaxis: antifungal (fluconazole/voriconazole), antiviral (acyclovir; valganciclovir for CMV prophylaxis), antibacterial (fluoroquinolone)
• CMV monitoring with PCR and pre-emptive ganciclovir
• For severe gut GvHD: bowel rest, Total Parenteral Nutrition (TPN)
• Fluid and electrolyte replacement (massive diarrhoea losses)
• Meticulous skin care; wound management; topical tacrolimus/steroids
• Psychological support

Chronic GvHD Treatment

• Prednisone 1 mg/kg/day +/- calcineurin inhibitor (cyclosporine/tacrolimus)
• Slow taper over months to years

• Ibrutinib (BTK inhibitor) - FDA approved 2017 for steroid-refractory cGvHD; response rate ~67%
• Ruxolitinib - FDA approved 2021 for steroid-refractory cGvHD; response rate ~49%
• Belumosudil (ROCK2 inhibitor) - FDA approved 2021; novel mechanism targeting fibrosis
• Extracorporeal photopheresis (ECP) - especially for skin/oral/liver cGvHD
• Rituximab (anti-CD20) - for cGvHD with B-cell pathology
• Mycophenolate mofetil
• Sirolimus
• Imatinib - for refractory sclerotic cGvHD (anti-fibrotic via PDGFR/TGF-β inhibition)
• Pomalidomide - immunomodulatory

• Eyes: artificial tears, cyclosporine eye drops, scleral contact lenses
• Oral: topical steroids, tacrolimus mouthwash, regular dental care
• Lungs (bronchiolitis obliterans): FAM protocol (fluticasone + azithromycin + montelukast); lung transplant last resort
• Oesophageal stricture: endoscopic dilation
• Vaginal sclerosis: topical oestrogen, dilators

Surgical Relevance of GvHD

1. Small bowel transplantation carries the highest risk of GvHD among all solid organ transplants because the transplanted bowel contains massive amounts of donor lymphoid tissue (Peyer's patches, mesenteric lymph nodes)
2. Transfusion-Associated GvHD (TA-GvHD): Fatal complication in immunocompromised surgical patients (post-bone marrow transplant, congenital immunodeficiency, neonates, Hodgkin lymphoma). Prevention: irradiate all cellular blood products (gamma irradiation 25 Gy) before transfusion
3. GvHD patients on heavy immunosuppression have: impaired wound healing, high infection risk (wound infections, anastomotic leaks), adrenal suppression (steroid cover perioperatively), thrombocytopaenia (haemorrhagic risk)
4. Gut GvHD may mimic acute abdomen - surgeons consulted for: intestinal obstruction, perforation, severe ileus
5. Liver GvHD may progress to cirrhosis - surgeons may encounter these patients for hepatic complications

Graft-Versus-Leukaemia (GvL) Effect

• The same alloreactive donor T-cells that cause GvHD also mediate the graft-versus-leukaemia (GvL) effect - killing residual leukaemic cells
• This is the therapeutic rationale for allogeneic BMT in leukaemia
• Complete T-cell depletion (to prevent GvHD) also abolishes GvL - increasing risk of leukaemia relapse
• Donor lymphocyte infusion (DLI) exploits GvL to treat relapse after transplant
• The GvHD-GvL dissociation remains a major challenge in transplant immunology

Prognosis

• Grade I-II aGvHD: 60-80% respond to steroids; good overall prognosis
• Grade III-IV aGvHD: Mortality exceeds 50%; gut and liver involvement = worst prognosis
• Steroid-refractory aGvHD: Overall survival <30% at 1 year
• Chronic GvHD with bronchiolitis obliterans: 5-year survival <30%
• GvHD remains the leading cause of non-relapse mortality following allogeneic HSCT
• Thrombocytopaenia in cGvHD is the single worst prognostic indicator

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26. HEMANGIOMA

Definition

• The most common benign tumor of infancy (affecting 4-10% of Caucasian infants)
• The most common benign tumor of the liver in adults (prevalence 0.4-7.3%)

Classification

A. True Hemangiomas (GLUT-1 positive)

1. Infantile Hemangioma (IH)

• Appears 1-4 weeks after birth; proliferates then involutes
• GLUT-1 (glucose transporter-1) positive - this distinguishes it from vascular malformations
• Divided into: superficial (strawberry), deep (subcutaneous), or compound (mixed)

2. Congenital Hemangioma

• Fully formed at birth; GLUT-1 negative
• RICH (Rapidly Involuting Congenital Hemangioma) - involutes by 14 months
• NICH (Non-Involuting Congenital Hemangioma) - persists permanently

B. Vascular Malformations (GLUT-1 negative - not true hemangiomas)

• Present at birth, grow proportionally with the child, NEVER involute
• Low-flow: capillary malformation (port-wine stain), venous malformation, lymphatic malformation
• High-flow: arteriovenous malformation (AVM), arteriovenous fistula

C. Cavernous Hemangioma (Liver)

• Most common benign hepatic tumor in adults
• Lined by flattened endothelium; large blood-filled spaces separated by fibrous septa
• Pathologically distinct from infantile hemangioma

D. Capillary Hemangioma

• Small, thin-walled capillaries arranged in lobular pattern

E. Other Types

• Synovial hemangioma (knee joint)
• Subglottic hemangioma
• Vertebral hemangioma
• Hepatic hemangioma

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PART A: INFANTILE HEMANGIOMA (IH)

Epidemiology

• Affects 4-10% of infants; more common in: females (3:1), premature infants, twins, Caucasians, low birth weight
• Most appear within first 2 weeks of life; sometimes noted as faint red macule or white patch at birth

Natural History - Three Phases

• Rapid growth driven by endothelial cell hyperplasia and angiogenesis
• Lesion becomes raised, firm, bright red (superficial) or bluish (deep)
• Peak growth velocity: 1-3 months
• 80% of final size reached by 3-5 months; growth complete by 9-12 months

• Gradual spontaneous regression
• Colour fades from bright red → dull red → grey
• Softening and flattening of lesion
• Markers: decreased GLUT-1 expression, increased apoptosis, fibrofatty replacement

• 50% complete by age 5
• 70% complete by age 7
• 90% complete by age 9
• Residual: fibrofatty tissue, redundant skin, telangiectasias, hypopigmentation, scarring

Sites of Occurrence

• Head and neck: 60% (face most common - cheek, lip, nose, eyelid, parotid region)
• Trunk: 25%
• Extremities: 15%
• Deep/visceral: liver, mediastinum, CNS (rare; associated with multiple cutaneous IH >5)

Complications (Indications for Treatment)

• Occurs at sites of maceration: lip, anogenital region, neck folds
• Painful, bleeds, prone to secondary infection
• Can result in scarring

• Periorbital/eyelid: Visual axis obstruction → deprivation amblyopia; astigmatism from corneal distortion - URGENT treatment needed
• Subglottic: Progressive biphasic stridor, airway compromise; present at 6-12 weeks; 50% have cutaneous hemangioma on head/neck
• Parotid/preauricular: External auditory canal obstruction → conductive hearing loss
• Nasal tip ("Cyrano" nose): Cartilage distortion if untreated
• Lip: Feeding difficulties

• Associated with large hepatic hemangiomas (diffuse hepatic involvement)
• Due to massive AV shunting within liver

• Large hepatic hemangiomas express type 3 iodothyronine deiodinase → excess degradation of thyroid hormones → consumptive hypothyroidism
• May require supraphysiological thyroid hormone replacement

• Large facial lesions, especially nasal tip, lip, ear, scalp
• Psychological impact on child and family

• Important note: KMP is NOT caused by classic infantile hemangioma
• Caused by Kaposiform Hemangioendothelioma (KHE) and Tufted Angioma
• Features: rapidly enlarging vascular tumor + profound thrombocytopenia + consumptive coagulopathy (DIC-like)
• Platelet count can drop to <10,000/μL
• Treatment: vincristine + sirolimus (preferred); steroids; embolization

• Posterior fossa malformations
• Hemangiomas (large segmental facial)
• Arterial anomalies (cerebrovascular)
• Cardiac defects and aortic coarctation
• Eye anomalies
• Sternal cleft / supraumbilical raphe

Investigations

• Clinical diagnosis in most cases (history of post-natal appearance + growth pattern)
• Ultrasound with Doppler: Confirms diagnosis; shows high-flow lesion with low RI
• MRI: For deep lesions, orbital involvement, or hepatic disease; T2 hyperintense; GLUT-1 immunostaining on biopsy
• Laryngoscopy: Flexible scope for subglottic hemangioma - compressible bluish submucosal mass
• Thyroid function tests: For diffuse hepatic IH
• Echocardiography: For PHACES syndrome, hepatic IH with cardiac failure

Management of Infantile Hemangioma

Indications for Active Treatment (approximately 10-12% of all IH)

1. Life-threatening: airway obstruction, high-output cardiac failure
2. Vision-threatening: visual axis obstruction, amblyopia risk
3. Ulceration with pain, bleeding, or infection
4. Functional compromise (feeding, hearing, urination)
5. Disfiguring location with risk of permanent deformity (nasal tip, lip, ear)
6. Large lesions with significant residue predicted

Medical Treatment

• Landmark discovery: Léauté-Labrèze et al. (Bordeaux, France, 2008) - serendipitous observation
• Dose: 1-3 mg/kg/day in 2-3 divided doses; most centres use 2 mg/kg/day
• Duration: Until 12 months of age minimum; usually 6-12 months total
• FDA approved formulation: Hemangeol (propranolol hydrochloride oral solution)
• Mechanism of action:
  • Immediate: vasoconstriction → colour fading within hours
  • Short-term: inhibition of angiogenesis (downregulation of VEGF, bFGF)
  • Long-term: induction of apoptosis in proliferating endothelial cells
• Response rate: >96%
• Contraindications: Cardiogenic shock, heart block, severe bradycardia, uncontrolled heart failure, asthma/reactive airway disease (relative), hypoglycaemia tendency
• Pre-treatment workup: Cardiac exam, ECG in infants <8 weeks or with cardiac concerns, blood glucose monitoring
• Side effects: Bradycardia, hypotension, hypoglycaemia (give with/after feeding), bronchospasm, sleep disturbances, cool extremities

• For small, thin, superficial lesions
• Beta-blocker applied topically; well-tolerated; minimal systemic absorption
• Particularly useful for eyelid lesions, small facial lesions
• Applied twice daily

• Prednisolone 2-3 mg/kg/day for 4-6 weeks, then taper
• Response rate 30-60%; significant side effects (cushingoid facies, growth retardation, adrenal suppression, hypertension, immunosuppression)
• Used when propranolol contraindicated

• Triamcinolone + betamethasone injection directly into lesion
• For small, focal, problematic lesions (eyelid, lip)
• Risk: skin atrophy, fat necrosis, periocular injection risk (retinal artery occlusion - use with extreme care)

• For propranolol/steroid failures, KMP
• IV infusion; side effects: peripheral neuropathy, constipation, hair loss

• mTOR inhibitor; increasingly used for complex, refractory, or mixed vascular lesions
• Effective for KMP associated with KHE
• Oral; requires blood level monitoring

Laser Treatment

• Treatment of choice for superficial IH, ulcerated IH, and residual telangiectasias post-involution
• Selectively targets oxyhaemoglobin in superficial vessels (selective photothermolysis)
• Multiple sessions required
• Limited penetration (1-2 mm) - not effective for deep lesions

• Deeper penetration
• For thicker, mixed lesions
• Risk of scarring higher

• For subglottic hemangioma (with propranolol as primary treatment now preferred)

Surgical Treatment

• Well-localized, pedunculated lesion amenable to simple excision
• Involuted IH with residual fibrofatty tissue causing disfigurement
• Failed or contraindicated medical therapy
• Ulcerated, non-healing lesion
• Before school age (3.5-4 years) to prevent psychological impact

• Direct excision with primary closure (elliptical/fusiform for small lesions)
• Geometric broken-line closure for facial lesions
• Serial excision for large lesions
• Combined laser + excision

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PART B: HEPATIC CAVERNOUS HEMANGIOMA

Epidemiology

• Most common benign liver tumor; prevalence 0.4-7.3% of population
• Female:male = 3:1; peak incidence 30-50 years
• Estrogen-responsive (grow during pregnancy, with OCP use)
• Usually solitary; right lobe predominant
• "Giant hemangioma" defined as >4-5 cm (some define >10 cm as "giant")

Pathology

• Macroscopy: Spongy, blood-filled, well-circumscribed; soft and compressible
• Microscopy: Large, irregular, blood-filled vascular spaces lined by flat endothelial cells; separated by fibrous septa; may show thrombosis, phleboliths, calcification in older lesions
• No malignant potential

Clinical Features

• Majority are asymptomatic - incidental finding on abdominal imaging
• Symptoms with giant hemangioma (>5 cm):
  • Dull right upper quadrant aching/discomfort
  • Early satiety, nausea, vomiting (mass effect on stomach)
  • Fullness and abdominal distension
• Kasabach-Merritt syndrome (rare): consumption coagulopathy with thrombocytopaenia - associated with giant lesions
• Spontaneous rupture - extremely rare (<1% of cases) but life-threatening haemorrhage
• Budd-Chiari syndrome - if caudate lobe hemangioma compresses hepatic veins
• Haemobilia (very rare)

Investigations

• Well-defined, hyperechoic (bright) lesion with posterior acoustic enhancement in small lesions
• Large lesions: heterogeneous echotexture
• Compressibility on probe pressure (pathognomonic but not always demonstrable)
• Doppler: peripheral slow flow; central flow absent (distinguishes from HCC which has internal arterial flow)

• Plain: Hypodense lesion
• Arterial phase: Peripheral nodular enhancement ("iris diaphragm" pattern; "cotton wool" appearance); begins at periphery
• Portal/venous phase: Progressive centripetal fill-in of contrast
• Delayed phase (5-10 min): Complete fill-in - lesion becomes isodense or hyperdense = "fill-in sign" - pathognomonic

• T1: hypointense
• T2: Markedly hyperintense - "light bulb sign" (distinctive - due to slow-flowing blood in large vascular spaces); no other common hepatic lesion shows this degree of T2 hyperintensity
• Gadolinium-enhanced: same peripheral nodular enhancement and centripetal fill-in as CT
• MRI sensitivity and specificity both >95%

• "Blood pool scan" - delayed images show increased activity ("hot spot") as RBCs accumulate in lesion
• Used when CT/MRI inconclusive; sensitivity ~90% for lesions >2 cm
• Non-invasive; no radiation to liver tissue

• Using SonoVue microbubbles
• Shows same peripheral nodular fill-in pattern as CT
• Useful for bedside assessment, avoids radiation

Differential Diagnosis

• Hepatocellular carcinoma (HCC)
• Hepatic metastases
• Focal nodular hyperplasia (FNH)
• Hepatic adenoma
• Simple hepatic cyst
• Hepatic abscess
• Cholangiocarcinoma

Management of Hepatic Hemangioma

Conservative Management (majority of patients)

• Most hemangiomas require no intervention - watchful waiting with imaging
• Stop oral contraceptive pills and hormone replacement therapy (estrogen promotes growth)
• Avoid contact sports for giant lesions (traumatic rupture risk)
• Repeat imaging at 6 months, then annually if stable
• Reassurance regarding zero malignant potential

Indications for Active Intervention

1. Kasabach-Merritt syndrome (thrombocytopaenia + coagulopathy)
2. Spontaneous or traumatic rupture with haemorrhage
3. Diagnostic uncertainty - cannot confidently exclude malignancy despite all imaging
4. Significant symptoms - pain, early satiety, compression symptoms in giant lesions refractory to conservative measures
5. Rapid growth on serial imaging
6. Pedunculated hemangioma - risk of torsion

Surgical Options

• Exploits the natural cleavage plane (compressed hepatic parenchyma) between hemangioma and surrounding liver
• Technique: hepatic inflow occlusion (Pringle manoeuvre), develop plane between pseudocapsule of hemangioma and compressed liver parenchyma, enucleate without opening lesion
• Advantages: Preserves maximum hepatic parenchyma; lower blood loss than anatomic resection; technically feasible; low morbidity

• For centrally located lesions where enucleation not feasible
• Segmentectomy, bisegmentectomy, lobectomy as required
• Higher blood loss and morbidity than enucleation

• Feasible for peripheral lesions, lesions in accessible segments (II, III, IVb, V, VI)
• Laparoscopic enucleation or resection
• Benefits: less blood loss, shorter hospital stay, earlier recovery

• Extreme last resort for unresectable, massive, symptomatic lesions causing hepatic failure
• Rarely indicated; only a handful of cases reported worldwide

Non-Surgical (Interventional) Options

• Selective catheterization and embolization of feeding hepatic artery branches
• Uses: PVA particles, coils, gelfoam
• Result: thrombosis and fibrosis of hemangioma
• Indications: palliative for unresectable symptomatic lesions; preoperative to reduce blood loss
• Limitations: incomplete response in many cases; risk of hepatic abscess, biloma, hepatic failure

• Thermal ablation via percutaneous or laparoscopic approach
• Best for small (<5 cm), peripheral, well-defined lesions
• Not suitable for large or centrally located lesions (bile duct injury risk)

• Similar to RFA; faster and larger ablation zones

• Emerging treatment for large, unresectable, symptomatic hemangiomas
• Limited evidence; shrinkage observed

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PART C: OTHER SURGICALLY IMPORTANT HEMANGIOMAS

Subglottic Hemangioma

• Presents at 6-12 weeks with progressive, intermittent biphasic stridor (worse with crying)
• 50% have associated cutaneous hemangioma, especially in "beard distribution" (chin, preauricular, submandibular, lower lip - "PHACES overlap")
• Diagnosis: flexible awake laryngoscopy - compressible, bluish, submucosal mass in subglottis (posterolateral wall)
• Treatment:
  • Oral propranolol - now first-line; dramatic response
  • CO2 laser excision - risk of scarring, stenosis; now less preferred
  • Open excision via laryngofissure
  • Tracheostomy - temporizing measure for severe airway compromise while awaiting propranolol response

Synovial Hemangioma

• Knee joint most common location
• Recurrent haemarthrosis (bloody joint effusion) from childhood
• Diagnosis: MRI - lobulated intra-articular mass, T2 hyperintense with foci of haemosiderin (hypointense)
• Treatment: surgical excision (open or arthroscopic)

Vertebral Hemangioma

• Most common primary bone tumor of spine (incidental finding on MRI in up to 10%)
• Characteristic appearance: "corduroy cloth" / "jail bars" pattern on lateral X-ray (vertical striations of thickened trabeculae)
• MRI: T1 and T2 hyperintense (fat and vascular components)
• Usually asymptomatic; treatment only for symptomatic lesions
• Symptomatic treatment options: vertebroplasty/kyphoplasty, embolization, radiation therapy, surgical decompression

Diffuse Neonatal Hemangiomatosis

• Multiple (>5) small cutaneous IH + visceral involvement (liver, brain, GI tract, lung)
• High-output cardiac failure, consumptive hypothyroidism, GI bleeding
• High mortality if untreated
• Treatment: propranolol, steroids; thyroid hormone replacement for hypothyroidism

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27. ROLE OF COLOUR DOPPLER IN SURGICAL CONDITIONS

Introduction and Basic Principles

1. B-mode (grey-scale) ultrasound - morphological/anatomical information
2. Colour flow mapping - direction and relative velocity of blood flow displayed in colour
3. Spectral (pulsed-wave) Doppler - quantitative velocity waveform analysis

Colour Coding Convention - BART

• Blue = Away from transducer
• Red = Toward transducer
• Aliasing (colour reversal/mosaic pattern) occurs when velocity exceeds the Nyquist limit (PRF/2)

Types of Doppler Ultrasound

Quantitative Parameters

• Peak Systolic Velocity (PSV) - cm/s
• End-Diastolic Velocity (EDV) - cm/s
• Resistive Index (RI) = (PSV - EDV) / PSV (normal 0.6-0.7 in most organs; renal transplant normal <0.7)
• Pulsatility Index (PI) = (PSV - EDV) / Mean velocity
• High RI = high resistance (downstream obstruction, vasospasm, rejection)
• Low RI = low resistance (arteriovenous fistula, hypervascular tumor)

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Applications in General Surgical Conditions

1. PERIPHERAL ARTERIAL DISEASE

Carotid Artery Disease

• Plaque characterization: Echogenicity (hypoechoic = soft/lipid-rich = unstable; hyperechoic/calcified = stable), surface irregularity, ulceration
• Stenosis grading using PSV:
  • PSV >125 cm/s at ICA = >50% stenosis
  • PSV >230 cm/s = >70% stenosis (NASCET criteria)
  • ICA/CCA PSV ratio >4 = >70% stenosis
  • Post-stenotic turbulence; spectral broadening
• Pre-intervention planning: Before carotid endarterectomy (CEA) or carotid artery stenting (CAS)
• Post-CEA surveillance: Detect restenosis, intimal hyperplasia, patch complications, pseudoaneurysm
• Carotid body tumor: Hypervascular mass splaying ICA and ECA ("lyre sign" on angiography; similar appearance on Doppler)

Lower Limb Arterial Occlusive Disease

• Assessment of stenosis/occlusion at every level: aorto-iliac, femoro-popliteal, infrapopliteal
• Normal waveform: triphasic (forward systolic, brief reverse diastolic, small forward diastolic)
• With stenosis: increased PSV at stenosis (>2× pre-stenotic = significant); monophasic waveform distally; turbulence
• Ankle-Brachial Index (ABI) - Doppler probe used to measure ankle systolic pressures (normal >0.9; claudication 0.5-0.9; critical ischaemia <0.5)
• Complete occlusion: absent colour fill; collateral vessels visible
• Pre-bypass planning: Identify suitable runoff vessels; assess vein graft
• Post-bypass surveillance: Graft velocity ratio (>3.5 at anastomosis = critical stenosis requiring revision); early detection of failing graft before thrombosis

Abdominal Aortic Aneurysm (AAA)

• Diagnosis and size measurement (transverse diameter)
• Mural thrombus extent
• Involvement of renal arteries and iliac vessels
• Post-EVAR (Endovascular Aneurysm Repair):
  • Type I endoleak: flow at proximal/distal landing zone
  • Type II endoleak: retrograde flow from lumbar/inferior mesenteric artery (colour Doppler ± CEUS)
  • Type III: fabric tear/junctional leak
  • Graft limb stenosis or thrombosis

Popliteal Artery Entrapment Syndrome

• Doppler with provocative manoeuvres (active plantar-flexion, passive dorsiflexion)
• Significant reduction in popliteal artery flow with manoeuvre = positive test

Acute Limb Ischaemia

• Confirm absent flow in affected vessels
• Identify level of occlusion (embolus vs thrombosis)
• Assess collateral flow
• Guide thrombolysis catheter placement

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2. VENOUS DISEASE

Deep Vein Thrombosis (DVT)

1. Non-compressibility of the vein lumen under probe pressure - gold standard criterion (sensitivity 95%, specificity 99% for femoropopliteal DVT)
2. Absent colour fill within the vein lumen (fresh thrombus may appear echogenic or anechoic)
3. Absent or reduced augmentation of venous flow with distal compression
4. Absent phasic variation with respiration (in proximal obstruction)
5. Direct visualisation of thrombus (echogenic material in lumen)

• Acute vs chronic DVT (acute = hypoechoic, soft, compressible walls; chronic = echogenic, calcified, non-compressible, may have partially recanalized lumen)
• Extent of thrombus
• Free-floating thrombus (high embolism risk)
• Iliac vein and IVC involvement

Varicose Veins and Chronic Venous Insufficiency

• Sapheno-femoral junction (SFJ) incompetence: Reflux >0.5 seconds on Valsalva manoeuvre or manual distal compression-release (reflux = blue flow reversing to red in GSV on Doppler)
• Sapheno-popliteal junction (SPJ) incompetence: Reflux at SPJ during calf compression
• Great Saphenous Vein (GSV) mapping: Mark GSV course, measure diameter, identify incompetent segments, tributaries
• Small Saphenous Vein (SSV) mapping: Variable anatomy; SPJ location varies (at or above popliteal crease)
• Perforator incompetence: Outward reflux (from deep to superficial) in perforators >3.5 mm with >500 ms reflux duration - especially Cockett's perforators (medial calf) and Hunterian perforator (medial thigh)
• Deep vein patency assessment: Confirm patent deep system before GSV ablation (patent deep system is prerequisite for treating superficial incompetence)
• Pre-EVLT/RFA mapping: Measure GSV diameter at SFJ and mid-thigh; depth from skin (must be >1 cm from skin for thermal safety)
• Pre-foam sclerotherapy mapping: Identify target vessels and anatomy

Venous Compression Syndromes

• May-Thurner Syndrome (Iliac Vein Compression Syndrome): Left common iliac vein compressed by overlying right common iliac artery against vertebral body; increased velocity at compression site; post-stenotic dilation; increased risk of left-sided DVT
• Nutcracker Syndrome: Left renal vein compression between superior mesenteric artery and aorta; increased velocity at compression; left renal vein dilation medial to compression

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3. RENAL AND TRANSPLANT VASCULAR CONDITIONS

Renal Artery Stenosis

• Screening for renovascular hypertension (fibromuscular dysplasia, atherosclerosis)
• Direct signs: Turbulent flow at stenosis; PSV >180 cm/s at renal artery; renal artery to aortic PSV ratio (RAR) >3.5
• Indirect (intrarenal) signs: Tardus-parvus waveform in intrarenal segmental/arcuate arteries: prolonged systolic acceleration time (AT >0.07 seconds), reduced AT (RI <0.5), rounded "parvus" waveform
• Guides decision for renal artery angioplasty/stenting

Renal Transplant Surveillance (Critically Important)

• Post-transplant routine monitoring: Daily/alternate day Doppler in early post-operative period
• Graft viability: Presence of arterial and venous flow
• Acute rejection: RI increases progressively (>0.8 suspicious; >0.9 = severe rejection); venous flow may be reversed in diastole
• Renal artery stenosis (post-transplant): PSV >250 cm/s at anastomosis; RAR >3; associated hypertension and rising creatinine
• Renal artery thrombosis: Absent arterial flow on colour Doppler - surgical emergency requiring immediate re-exploration
• Renal vein thrombosis: Absent venous flow; reversed diastolic arterial flow; enlarged oedematous graft
• Arteriovenous fistula / Pseudoaneurysm (biopsy complications):
  • AVF: turbulent high-velocity low-resistance arterial flow with arterialized venous signal ("to-and-fro" adjacent flow)
  • Pseudoaneurysm: pulsatile cystic lesion with "yin-yang" swirling colour pattern; "to-and-fro" flow in neck
  • Most small iatrogenic AVFs and pseudoaneurysms resolve spontaneously; large ones require intervention (thrombin injection for pseudoaneurysm)
• Ureteric obstruction (hydronephrosis): Elevated RI in obstructed kidney; absent ureteric jets in bladder

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4. HEPATIC AND PORTAL VASCULAR CONDITIONS

Portal Hypertension

• Portal vein diameter >13 mm (normal <12 mm)
• Portal blood flow velocity <16 cm/s (reduced / sluggish flow)
• Hepatofugal (reversed) portal flow - hallmark of severe portal hypertension (hepatic encephalopathy risk)
• Portosystemic collaterals: Para-umbilical vein recanalization (caput medusae), splenorenal shunt, coronary/left gastric vein dilation
• Splenomegaly: Spleen size and splenic vein dilation
• Ascites detection
• Post-TIPSS monitoring: Shunt patency; velocity within TIPSS stent (normal >60-90 cm/s; <50 cm/s = stenosis/dysfunction); restored hepatopetal flow

Portal Vein Thrombosis

• Absent colour fill in portal vein
• Echogenic intraluminal thrombus
• Cavernous transformation (chronic PVT): serpiginous collateral vessels replacing thrombosed portal vein
• Tumour thrombus (HCC): expansile, arterialised flow within thrombus (distinguishes from bland thrombus)

Budd-Chiari Syndrome

• Absent or reversed hepatic vein flow
• Caudate lobe hypertrophy (drains separately to IVC)
• Intrahepatic collaterals ("spider web" pattern)
• May show IVC compression/thrombosis

Liver Transplant Surveillance

• Hepatic Artery Thrombosis (HAT):
  • Most devastating complication; occurs days to weeks post-transplant
  • Doppler: absent hepatic artery signal = surgical emergency requiring immediate re-exploration / thrombolysis / retransplantation
  • Early HAT: RI <0.5 or absent diastolic flow, diminished systolic velocities (tardus-parvus pattern)
  • Sensitivity of Doppler for HAT: 92-100%
• Hepatic Artery Stenosis (HAS):
  • PSV >200 cm/s at anastomosis + tardus-parvus in intrahepatic vessels
  • Treated by angioplasty or surgical revision
• Portal Vein Thrombosis/Stenosis:
  • Absent/reduced portal flow; PSV <50 cm/s or >100 cm/s (stenosis)
• Hepatic Vein Outflow Obstruction:
  • Monophasic (loss of triphasic waveform), reversed, or absent hepatic vein flow
  • RI elevation in hepatic arteries
• Biliary complications indirectly suggested by hepatic artery problems (bile ducts rely on hepatic artery for supply)

Hepatocellular Carcinoma (HCC)

• Internal tumour vascularity (arterial flow within lesion)
• Portal vein tumour thrombus (arterialised flow within PV = tumour thrombus)
• Helps distinguish HCC from haemangioma (haemangioma has peripheral, slow, venous-type flow)

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5. THYROID AND PARATHYROID CONDITIONS

Thyroid

• Graves' Disease / Thyrotoxicosis: Diffusely increased vascularity throughout gland - "inferno pattern" (brilliant colour throughout on power Doppler) due to massively increased blood flow; thyroid artery PSV >70 cm/s (normal <30 cm/s)
• Hashimoto's Thyroiditis: Variable vascularity; heterogeneous echotexture
• Thyroid Nodule Assessment:
  • Central vascularity within nodule - more suspicious for malignancy
  • Peripheral (rim) vascularity - more suggestive of benign colloid nodule
  • Entirely avascular - colloid cyst
  • Doppler vascularity pattern used in conjunction with TIRADS scoring and FNA decision
• Post-thyroidectomy haematoma: Identify active bleeding vessel for targeted exploration/ligation

Parathyroid

• Parathyroid Adenoma Localization (Pre-operative):
  • Highly vascular, well-defined hypoechoic lesion posterior/inferior to thyroid
  • Characteristic "vascular pedicle sign" - single polar feeding artery entering the adenoma (sensitivity ~80%; specificity >90%)
  • Used alongside sestamibi (Tc-99m MIBI) scan and 4D-CT for pre-operative localization
  • Guides minimally invasive parathyroidectomy (MIP)
  • Doppler-guided FNA with PTH washout for confirmation

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6. SCROTAL CONDITIONS

Testicular Torsion (Surgical Emergency)

• Most critical application in acute scrotum
• Colour Doppler shows absent intratesticular blood flow (sensitivity 86-100%, specificity 97-100%)
• Always compare with contralateral testis (contralateral may show reactive hyperaemia)
• Critical caveat: Presence of some flow does NOT exclude partial torsion or early/intermittent torsion
• If absent flow + clinical suspicion of torsion: immediate surgical exploration WITHOUT waiting for further imaging
• Differential: epididymo-orchitis (markedly increased vascularity), testicular tumour, haematocele

Epididymo-Orchitis

• Markedly increased vascularity of epididymis and testis
• Enlarged, heterogeneous epididymis
• Reactive hydrocele
• Scrotal wall oedema

Varicocele

• Dilated (>3 mm) pampiniform plexus veins in upright position
• Retrograde flow (reflux) during Valsalva manoeuvre lasting >2 seconds
• Graded:
  • Grade I: Doppler demonstrable only (subclinical)
  • Grade II: Palpable on Valsalva
  • Grade III: Visible without Valsalva
• Pre-varicocelectomy/embolization planning; left-sided varicocele in older male → exclude left renal vein obstruction/RCC (thrombus in left renal vein)
• Infertility workup

Testicular Tumour

• Internal vascularity (vascular lesion = tumour; avascular areas = necrosis/haemorrhage)
• Reactive epididymis and lymph node assessment
• Post-orchidectomy surveillance

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7. OBSTETRIC AND GYNAECOLOGICAL CONDITIONS (Surgical Relevance)

Ectopic Pregnancy

• "Ring of fire" sign - peripheral hypervascularity around adnexal mass on colour Doppler
• Absent intrauterine pregnancy
• Combined with serum beta-hCG levels for diagnosis
• Guides management decision (medical methotrexate vs surgical salpingectomy)

Ovarian Torsion

• Absent or markedly reduced ovarian blood flow
• Important: Presence of flow does NOT exclude torsion (venous occlusion occurs before arterial - blood may still enter)
• Enlarged, oedematous ovary with peripheral follicles
• Clinical suspicion still mandates surgical exploration despite normal Doppler

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8. VASCULAR TRAUMA

• Pseudoaneurysm: Pulsatile cystic lesion adjacent to vessel; "yin-yang" swirling colour pattern on colour Doppler; "to-and-fro" waveform in neck; most common after catheterization procedures
  • Treatment: ultrasound-guided thrombin injection (98% success) or manual compression; surgical repair for large/infected/failed percutaneous treatment
• Arteriovenous Fistula (post-traumatic/iatrogenic): High-velocity, turbulent, low-resistance arterial flow; arterialized (pulsatile) venous signal adjacent
• Intimal Flap / Dissection: Echogenic linear intraluminal structure; true and false lumen flow differentiation
• Haematoma: No internal flow (distinguishes from pseudoaneurysm)
• Zone of injury mapping - guides surgical approach

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9. INTRAOPERATIVE DOPPLER

Free Flap Surgery (Microvascular Reconstruction)

• Pre-operative perforator mapping: Handheld pencil Doppler identifies and marks perforator vessel locations on skin for DIEP flap, ALT flap harvest
• Intraoperative anastomosis assessment: Handheld Doppler confirms flow through anastomosis after completion; identifies kinking, thrombus
• Post-operative free flap monitoring: Implantable Doppler probes (Cook-Swartz) on pedicle vessel for continuous monitoring of flap perfusion

Bowel Viability Assessment

• Handheld Doppler or laser Doppler flowmetry to assess mesenteric/mural blood flow before anastomosis
• After intestinal resection in ischaemia cases

Neurosurgery

• Intraoperative transcranial Doppler (TCD) or direct Doppler on exposed vessels
• After cerebral aneurysm clipping: confirm parent vessel patency, exclude inadvertent clip on perforator
• AVM resection: assess residual flow

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10. TUMOUR VASCULARITY ASSESSMENT

Breast

• Benign nodules: Peripheral vascularity; low velocity
• Malignant lesions: Internal vascularity; irregular, randomly distributed vessels; high velocity; low resistance
• Axillary lymph nodes: Cortical thickness >3 mm + absent/eccentric hilum = suspicious for metastasis
• Guides FNA/core biopsy

Soft Tissue Masses

• Lipoma: Avascular (no internal flow)
• Malignant soft tissue tumour: Internal vascularity with irregular neovascularisation
• Ganglion: Avascular cystic structure

Colorectal Cancer

• Tumour vascularity; mesenteric lymph node assessment; portal vein involvement

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11. SPECIFIC SURGICAL CONDITIONS - ADDITIONAL

Subclavian Steal Syndrome

• Stenosis or occlusion of subclavian artery proximal to vertebral artery origin
• Reversed flow in ipsilateral vertebral artery (hallmark finding) - blood "steals" from posterior circulation to supply the arm
• Spectral Doppler shows: initially antegrade flow in vertebral that reverses with arm exercise; in complete steal, permanently reversed vertebral flow

Visceral Artery Aneurysm

• Splenic artery most common (60%)
• Detected incidentally; size, morphology, relationship to vessels
• Turbulent flow within aneurysm sac; neck identification

Mesenteric Ischaemia

• Superior mesenteric artery: PSV >275 cm/s = significant stenosis
• Celiac artery: PSV >200 cm/s = significant stenosis
• In acute mesenteric ischaemia: absent SMA flow or very high-resistance pattern

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Advantages of Colour Doppler Ultrasound

1. Non-invasive - no puncture, no radiation, no contrast required (standard Doppler)
2. Real-time and bedside applicable (portable machines)
3. Combined anatomical + functional information simultaneously
4. Dynamic assessment possible (Valsalva, compression manoeuvres, limb exercise)
5. Serial monitoring - can be repeated without cumulative harm
6. Cost-effective compared to CT angiography or MRA
7. Guides intervention directly (US-guided thrombin injection, foam sclerotherapy)
8. No nephrotoxicity - suitable for renal-impaired patients

Limitations

1. Operator-dependent - significant learning curve; experienced sonographer essential
2. Angle-dependent - optimal at <60° to vessel axis; vessels running perpendicular to beam poorly assessed
3. Limited in obese patients and those with excessive bowel gas or open wounds
4. Calcification causes acoustic shadowing - vessels in calcified segments not assessable
5. Aliasing artefact at high velocities - overcome by adjusting PRF (pulse repetition frequency)
6. Cannot replace CT/MR angiography for complex planning, preoperative mapping of deep vessels
7. Deep vessels (aorta, iliac in obese): limited penetration; B-mode may be adequate for size but Doppler accuracy reduced

Recent Advances

1. Contrast-Enhanced Ultrasound (CEUS)

• Microbubble contrast agents (SonoVue/Lumason - sulfur hexafluoride microbubbles; Definity - perflutren)
• Pure intravascular agents (unlike CT/MRI contrast which extravasate)
• Applications:
  • Liver lesion characterization (HCC vs haemangioma vs metastasis vs FNH)
  • Endoleak detection after EVAR (superior to CT in some studies for Type II endoleak)
  • Renal mass characterization
  • Bowel wall vascularisation in Crohn's disease
  • Peripheral perfusion assessment
• Advantages: No radiation, no nephrotoxicity, no thyrotoxicity risk, real-time

2. 3D/4D Doppler Ultrasound

• Volumetric flow measurement
• Three-dimensional reconstruction of vascular anatomy
• Assessment of tumour vascular architecture

3. Elastography Combined with Doppler

• Shear wave elastography assesses tissue stiffness
• Combined with Doppler for liver fibrosis staging, lymph node assessment

4. High-Frame-Rate / Ultrafast Doppler

• Plane-wave compounding enables very high temporal resolution
• Can image very slow flows; functional brain imaging

5. AI-Assisted Doppler Analysis

• Machine learning algorithms for automated spectral waveform analysis
• Automated plaque characterization and stenosis grading
• Reducing operator variability

6. Intravascular Ultrasound (IVUS) with Doppler

• Catheter-based; assesses vessel wall from inside
• Combined with fractional flow reserve (FFR) for coronary and peripheral interventions

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