GI - Hepatomegaly and Liver cancer Flashcards
Malignant Ddx of hepatomegaly
Primary liver tumour
Hepatocellular carcinoma (HCC, 85%)
Cholangiocarcinoma (CC)
Secondary tumours
Solid organ malignancies: GI, other primaries
Haematological: leukaemia, lymphoma
Benign ddx of hepatomegaly
Infiltrative/replacement of parenchyma
Fat: alcoholic liver disease, NAFLD
Metabolic: Wilson’s disease, haemochromatosis, amyloidosis, other infiltrative diseases
Cysts: simple liver cysts, polycystic liver
Abscess: pyogenic, amoebic
Benign tumours:
Expansion of parenchyma
Hepatitis: infective, ischaemic, metabolic, autoimmune
‘Obstructive’
Vascular: Rt HF, TR, Budd-Chiari syndrome
Biliary: PBC, biliary atresia
Outline brief history taking for hepatomegaly
Pain: usually indicates significant enlargement stretching the liver capsule
Jaundice ± obstructive jaundice
GI symptoms, esp changes in bowel habits
Constitutional symptoms and fever
Systemic screen for any primary
Hx and RFs for chronic liver disease
FHx for malignancy
Outline P/E for hepatomegaly
General: cachexia, pallor, jaundice
Cervical LNs
Peripheral stigmata of chronic liver disease
Hepatomegaly itself: upper and lower border, surface, edge, consistency, tenderness, bruit
Other abd findings: splenomegaly, other masses, ascites
PR exam for rectal masses
Ddx diffuse smooth, firm hepatomegaly
Alcoholic liver disease
Haematological malignancies
Ddx irregular, hard hepatomegaly
HCC
Cholangiocarcinoma
Secondary malignancies
First-line investigations for hepatomegaly
□ Bloods: CBC, L/RFT, clotting profile, Viral hepatitis serology, tumour markers (AFP, CEA, CA19-9)***
□ Imaging: CXR, USG, triphasic CT, dynamic contrast MRI
□ Endoscopy: upper and lower (if suspicious for GI primaries)
□ Biopsy: plan for palliative radio-chemotherapy, defining cancer type for operability
- US-guided FNAC
- Tru-cut core biopsy
Liver anatomy:
Arterial and venous supply
Portal hepatis structure
□ Blood supply: 80% from portal v., 20% from hepatic artery
□ Venous drainage via left, middle and right hepatic veins
□ Porta hepatis structures:
→ CBD: towards the Right
→ Hepatic Artery: towards the Left
→ Portal Vein: towards the Inferior side
→ Divides into left and right branches 2cm from liver
Liver anatomy:
Ligaments and peritoneal reflections
→ Triangular ligament superiorly fixing superior surface of liver onto diaphragm
→ Falciform ligament anteriorly attaching anterior surface of liver onto abd wall
→ Ligamentum teres as remnant of umbilical v. running within falciform ligament to umbilicus
→ Ligamentum venosum as remnant of ductus venosus running along posterior surface of liver from lig. teres to IVC
→ Hepatoduodenal lig (lesser omentum) running from posteroinferior surface of liver to stomach, laterally bound by hilar vessels (f. of Winslow)
List benign liver tumors
Hepatic Haemangioma
Hepatic Adenoma
Focal Nodular Hyperplasia (FNH)
Hepatic Haemangioma /
Demographic
Pathogenesis
S/S
Complications
Demographic: Most common benign liver cancer, 30-50y, M:F ≈ 1:3
Pathogenesis: congenital vascular malformation, enlarge by ectasia (not hyperplastic), well-circumscribed lesion
S/S;
- Asymptomatic, incidental finding
- Vague RUQ discomfort/fullness: due to liver capsule stretch
- Mass effect: nausea, anorexia, early satiety
- Acute abd pain due to intra-tumour thrombosis/bleeding
- cutaneous haemangioma
Complications
- High output HF
- Hypothyroidism: ↑T3 deiodinase activity
- Kasabach-Merritt syndrome
Hepatic haemangioma /
Dx investigations with typical findings
Mx
Dx:
- USG: well-demarcated, homogeneous, hyperechoic mass with high vascularity
- Triphasic CT
Pre-contrast: well-demarcated hypodense lesion
Early phase: characteristic peripheral nodular enhancement
Delayed phase: remains enhancing - MRI: smooth, well-demarcated homogenous mass
***FNAC: contraindicated! (risk of severe haemorrhage)***
Mx:
Observation for asymptomatic esp if small, eg. <1.5cm
Serial imaging for larger asymptomatic tumours >5cm
Surgical resection for symptomatic or complicated lesions
Non-surgical Tx: low dose RT, arterial embolization, IFN-α-2A if large, unresectable
Hepatic Adenoma /
Demographic
Risk factors
Pathogenesis
Demographics: uncommon, usually in young women (M:F = 10:1)
RFs:
→ Strongly a/w oestrogen use (HRT/OCP
→ Anabolic androgen use
→ Others: glycogen storage diseases, genetic mutations, pregnancy
Pathology: benign proliferation of hepatocytes (NOT ‘hepatoma’), 70-80% solitary
Hepatic adenoma /
S/S
□ Asymptomatic in majority
□ Episodic RUQ/epigastric pain due to hepatomegaly, bleeding or tumour necrosis
□ Spontaneous rupture + intra-abd bleed: sudden severe pain + hypotension
□ Abdominal mass or hepatomegaly
□ Malignant transformation: risk ~8-13%,
Hepatic adenoma /
Dx investigations with typical results
Mx
Dx:
□ USG: non-specific well-demarcated hyperechoic SOL of liver
□ Triphasic CT: iso/hypodense (precontrast) → peripheral enhancement (early) → centripetal flow (portal venous) → iso/hypodense (late)
□ Others: MRI, 99mTc sulphur colloid scan, angiography
Mx:
□ Cessation of OCP + interval imaging for asymptomatic small adenomas
□ Surgical resection if symptomatic or >5cm
□ Avoid pregnancy/ undergo RFA before attempting pregnancy
Focal Nodular Hyperplasia of liver /
Demographic
Pathogenesis
S/S
Dx and Mx
HCC *
Demographics
Risk factors
Demographics: M:F = 3.3:1, mostly at age >50y (peak at 60s)
Chronic liver disease-related RF:
- Chronic hepatitis B (both cirrhotic and non-cirrhotic)
- α1-antitrypsin deficiency
- Cirrhosis:
Alcoholic
Metabolic: haemochromatosis, Wilson’s disease, NAFLD
Autoimmune: PBC, AIH, PSC
Viral: chronic hepatitis B, C
Non-alcoholic liver disease-related
- Aflatoxins: mycotoxins found in contaminated corn, soybeans, peanuts
- *- Smoking, alcoholism**
- *- Obesity and DM**
- Prior gallstone disease/cholecystectomy
- Diet
HCC
Differentiate macroscopic vs microscopic subtypes
Biological behavior
Macroscopic types: massive (usu non-cirrhotic), nodular, diffuse (HCV-related)
Microscopic types:
→ Non-fibrolamellar type: vast majority, a/w HBV and cirrhosis
→ Fibrolamellar carcinoma (FLC): very rare (<1%)
Biological behaviour:
→ Very vascular tumour with high propensity for venous invasion (portal and hepatic vv)
→ Rapid tumour growth
HCC
Routes of metastasis
Spread:
→ Transvenous (intrahepatic portal/hepatic vv. and bile ducts)
→ Lymphatic to intra-abdominal LNs (uncommon, 1-8%)
→ Haematogenous to lungs (most common), bones, adrenals (less common)
→ Transcoelomic to peritoneum (rare, but frequently missed on CT)
Reasons for poor prognosis of HCC /
Majority have underlying cirrhosis (~80% for HBV, 100% for HCV)
Field cancerization: early or premalignant lesions present in other parts of liver
Asymptomatic in early stages: usually symptomatic only when tumour >8cm
Early intravenous spread: a/w early mets or portal vein thrombosis
HCC *
Clinical presentation, S/S
Local, constitutional, paraneoplastic, metastatic
□ Asymptomatic (50%): usually by AFP/USG surveillance for Hep B or cirrhosis
□ Local:
→ RUQ/epigastric pain: vague, dull and persistent, capsular distension
→ Local mass effect: early satiety, N/V, palpable mass in upper abdomen
→ Obstructive jaundice
→ Decompensated cirrhosis: causes further deterioration of LFT
→ Tumour rupture (<3%): sudden onset of severe abd pain, generalized peritonitis and shock
□ Constitutional symptoms (80%): LOW, LOA, malaise, fever
□ Paraneoplastic syndrome:
→ HypoGly due to ↑metabolic needs
→ Erythrocytosis due to EPO secretion
→ Fever due to central tumour necrosis (reactive)
→ Others: hyperCa (PTHrP)
□ Metastatic: bone pain, dyspnoea
HCC
Diagnostic investigations and typical findings
Serological (2)
Imaging (5)
Bx (1)
Elevated AFP >400ng/mL
Hepatitis serology: HBsAg, anti-HCV
Imaging:
- USG hepatobiliary system: >1cm, interval growth, hypoechoic mass
- Triphasic CT scan*****: Arterial phase: arterial enhancement, Portal venous phase: washout, Delayed phase: washout ± rim enhancement
- Dynamic contrast MRI: early arterial enhancement with rapid washout ± late rim enhancement
- Hepatic angiogram w/ lipiodol + post-lipiodol CT scan: dense staining due to neovascularization
- Dual tracer PET-CT with 11C-acetate and 18-FDG as tracers in uncertain cases
- *Liver biopsy by FNAC/trucut**
- for unresectable cases due to ↑risk of tumour tract seeding
AFP for HCC diagnosis
Sensitivity and specificity
Function in HCC management
Confounding causes of elevation
400ng/mL (Sens <20%, Spec >95%) → almost diagnostic in high-risk individuals
Function:
Prognostic value: very high AFP predicts ↑tumour load, ↑aggressiveness, ↑risk of metastasis
Post-operative surveillance
- *Causes of ↑AFP:**
- Liver regeneration: HCC, acute/chronic viral hepatitis, cirrhosis
- Others: gonadal tumours (germ cell and non-germ cell), pregnancy, gastric CA
List curative treatment options for HCC (3)
List palliative treatment options for HCC (5)
- *Curative:**
- *- Hepatectomy**
- *- Liver transplant**
- *- Local ablation:** radiofrequency ablation, microwave ablation, percutaneous ethanol ablation, cryoablation, HIFU
- *Palliative:**
- *- Embolization: Trans-arterial chemo-embolization (TACE), Trans-arterial radio-embolization (TARE)**
- Radiotherapy
- *- Targeted therapy (e.g. sorafenib)**
- Immunotherapy
- Supportive care
Indications for Hepatectomy vs liver transplant vs local ablation for HCC
Hepatectomy: Resectable disease, with no vascular or extra-hepatic invasion, good reserve liver function
Liver transplant: Child C disease meeting Milan/UCSF criteria, Unresectable disease meeting transplant criteria
Local ablation: unresectable small and solitary (<5cm) or oligofocal tumours (<3 nodules <3cm)
Indications for embolization vs radiotherapy vs targeted therapy vs immunotherapy for HCC Palliation
Embolization - 1st line for unresectable, large or multifocal HCCs with satisfactory liver fx and no Extrahepatic vascular invasion/metastasis (EVM)
Radiotherapy - after failure of other locoregional techniques if no EVM
Targeted therapy and Immunotherapy- 1st line for patients with EVM
Cholangiocarcinoma - Check JC63
Common primaries of secondary liver cancer
GIT primaries (MOST COMMON): Colon, stomach, pancreas, Biliary tree
Others: Lung, Kidney, Urogenital
Treatment of metastatic liver cancer
- *Hepatic resection:**
- *-** Prolong survival in colorectal metastasis with neoadjuvant chemotherapy
- Palliation for carcinoid or neuroendocrine tumors with TACE/ TARE
Local ablation e.g. RFA
Other metastasis: resection/locoregional therapy usually has NO role
Metastatic liver cancer
First-line investigations
Workup:
Tumour markers:
→ CEA/CA19-9: ↑ in some cases with primary GI malignancy (and CA lung if CEA)
→ AFP: for consideration of HCC
Triphasic CT scan:
→ Hypovascular mets (GI primary: colon, stomach, pancreas)
→ Hypervascular mets (neuroendocrine, RCC, breast, melanoma, thyroid)
Imaging the primary: CXR, CT, MRI, PET-CT
Liver Bx: FNAC/Trucut (usually only if unresectable)
Why is DVT related to GI cancer
Cancer is a pro inflammatory state and pro-coagulation state
Tumour can obstruct lymphatic return and venous return causing stasis
Immobilisation
