Hepatocellular Carcinoma ( HCC) Flashcards

Question

Percutaneous ethanol injection (PEI)

Answer 1

Under ultrasound, 95% ethanol is injected into the tumor. - Indicated for HCC < 2 cm, located near major vessels (where RFA not feasible) - Associated with incomplete necrosis in most HCCs >2 cm and a high local recurrence rate (49%). - Percutaneous acetic acid injection, shows no advantages to PEI. - Largely replaced by RFA. [DOI:10.1053/j.gastro.2004.09.003, DOI:10.1136/gut.2004.045203, DOI:10.1053/j.gastro.2005.04.009, DOI:10.1148/radiol.2281020718]

Answer 2

Uses a device with argon or helium gas to decrease temperature by Thomson effect around the needle and induce tissue freezing and vascular injury. An ice ball can be visualized with US, CT or MRI during ablation and helps to monitor treatment. - ‘‘**cryo-shock**”, a life-threatening condition resulting in multi-organ failure, severe coagulopathy and disseminated intravascular coagulation following cryoablation

Answer 3

Mainly Surgical Resection or Transplant **Surgical Resection** - Surgical resection should be the **treatment of choice** for localized HCC in the **absence of underlying cirrhosis** (Level 2, Strong Recommendation). - In patients with **cirrhosis**, surgical resection should be considered the treatment of choice for patients with **limited tumor burden, well-compensated cirrhosis without clinically significant portal hypertension, and an adequate FLR**(Level 2, Strong Recommendation). - Routine postoperative **surveillance** should be performed to detect recurrence using **contrast-enhanced multiphasic CT or MRI every 3–6months for all patients with HCC following liver resection** (Level 3, Strong Recommendation).

Answer 4

- Single stage vs Multi stage. - **Margin: 1 cm** - Liver resection can be offered to single HCC regardless of its size with a definitive survival advantage over other treatments – especially for tumor >5 cm – surgical feasibility may vary according to the liver volume and function-preservation principles.

Answer 5

1) Anatomic resections - (A-A’) removes entirely the tumor-bearing portal branches bordered by the landmark veins. Caudate lobe can be removed as an isolated resection or as a component of more extensive resections 2) None Anatomic resections - Limited resections of a small portion of liver without respect to the vascular supply, tumor-bearing 3rd-order portal region is not fully removed (B-B’). After non-anatomic resection of HCC some part of tumor-bearing portal region is left, which is at high risk of tumor recurrence

Answer 6

**Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS)** - **1st step** - liver parenchyma is transected along the intended line of resection and the future liver remnant cleaned by partial resections from all tumor tissue in the case of bilobar tumors. - Portal ligation of the larger liver lobe that will be removed. - The patient is then allowed to recover for a period of 1-2 weeks. - **2nd step** - the deportalized liver is removed to render the patient completely tumor-free.

Answer 7

**Intra-operative** - Bleeding - Intermittent Pringle maneuver (15 min clamp then release for 5 min) - Maintaining low CVP (< 5 mmHg) with minimal acceptable U/O (0.5 ml/kg/hr) and advance in instrument (ABC). - CUSA – Cavitron Ultrasonic Surgical Aspirator **Post-operative** - Hypophosphatemia - Common & occur on D2 to D5 post-op, Underlying pathophysiology not fully defined, generally attributed to increased consumption of ATP by regenerating liver and transient renal loss. - Liver failure Predictor of Liver Failure and Death After Hepatectomy **50-50 criteria** [DOI: 10.1097/01.sla.0000189131.90876.9e] - PT <50% and - Serum Bilirubin >50 μmol/L. - On POD 5, - patients who met this criterion had a 59% risk of early postoperative mortality, compared with 1.2% risk of mortality if the criteria were not fulfilled. - Biliary complications - 6 – 12% involve bile leaks leading to intra-abdominal sepsis

Answer 8

**Pre-operative Portal Vein Embolization** (**PO-PVE**): - Aim for redistribution of portal venous blood & hepatotropic factors to achieve substantial hypertrophy of non-embolized lobe of liver i.e. future remnant liver (FRL), resection planned in 4 weeks. - It also aims to reduce post-operative liver failure and prevent post-op portal hypertension. - - **Contraindications** - Overt portal hypertension (absolute) - Relative: tumor invasion of portal vein, occlusion of portal flow, biliary tree obstruction, mild portal hypertension, renal failure and uncorrected coagulopathy. - **Post embolization syndrome (PES):** Nausea, vomiting, fever, abdominal pain, haemobilia, hemoperitoneum, arteriovenous fistula, transient liver failure, subcapsular hemorrhage, portal vein thrombosis etc. **🔹 Why Does PES Happen?** PES occurs as a result of: **1) Tissue Ischemia & Necrosis:** PVE blocks blood flow to the embolized liver segments (usually the right lobe). This causes hepatocyte ischemia and localized necrosis, triggering inflammation. **2) Inflammatory Response & Cytokine Release:** The ischemic tissue releases pro-inflammatory cytokines (TNF-α, IL-6). This leads to systemic inflammatory symptoms like fever and leukocytosis. **3) Toxic Metabolite Release:** Necrotic hepatocytes release intracellular toxins, contributing to nausea, malaise, and pain. **4) Temporary Liver Dysfunction:** The liver needs time to adapt and regenerate (especially the future liver remnant, FLR). This may lead to transient elevation of liver enzymes (ALT, AST, bilirubin). **Pre-operative hepatic artery embolization**: - To reduce vascularity, induce tumor necrosis (reduce tumor volume) & limit spillage and vascular dissemination of viable tumor during resection, especially in primary HCC and neuroendocrine tumor. Both procedures can be achieved via Endovascular methods using (custom balloon occlusion catheters, fibrin glue, ethiodized oil, gelatin sponge, sclerosants, coils) or Surgical.

Answer 9

- Liver transplantation should be the treatment of choice for **transplant-eligible patients with early-stage HCC** occurring in the setting of clinically significant **portal hypertension and/ or decompensated cirrhosis**(Level2,Strong Recommendation). - Liver transplantation should be the treatment of choice for transplant-eligible patients with HCC that recur **within Milan criteria after surgical** resection (Level 3, Strong Recommendation). - The Milan criteria**(one lesion less than 5cm or two to three lesions between 1 and 3cm)** has been well established as the standard for optimal patient selection.

Answer 10

- Patients with **BCLC Stage B** HCC should be treated with **transarterial chemoembolization** (Level 1, Strong Recommendation). - AASLD advises **radioembolization as an alternative therapy** to chemoembolization in patients with BCLC Stage B HCC (Level 3, Strong Recommendation). - Transarterial therapies should be **performed in a selective/segmental fashion** (over lobar treatment) whenever possible given a lower risk of hepatic dysfunction (Level 5, Strong Recommendation). - AASLD advises **against the combination of systemic therapy with transarterial therapies** for BCLC Stage B HCC outside of a clinical trial setting (Level 2, Strong Recommendation) - AASLD advises **systemic therapy** in patients with intermediate HCC who are unsuitable for or refractory to locoregional therapies **due to contraindications, worsening hepatic dysfunction, progression of HCC, or lack of objective response** (Level 3, Strong Recommendation)

Answer 11

- Response evaluation criteria in solid tumors (RECIST) v1.1 is the standard tool to measure response and progression in oncology. - mRECIST criteria has been proposed to adapt RECIST criteria to particularities of HCC, enabling capture of antitumoral response without observed shrinkage after local and systemic therapies. - mRECIST has become the standard tool to assess radiological response after locoregional therapy for patients with early and intermediate stages of HCC, whereas both RECIST 1.1 and mRECIST are recommended for patients with advanced-stage HCC undergoing systemic therapy.

Answer 12

**Trans arterial chemoembolization (TACE)** Rationale for TACE - HCC exhibits intense arterial neo-angiogenic activity during its progression, thus intra-arterial infusion of a cytotoxic agent followed by embolization of tumor-feeding blood vessels will result in a strong cytotoxic and ischemic effect targeted to the tumor since this tends to become entirely fed by arterial inflow, unlike the surrounding parenchyma which receives the majority of inflow through the portal system. **Indications** - Best candidates - patients with uni- or pauci-nodular disease without vascular invasion or metastases, who are asymptomatic and have a Child-Pugh stage of ≤B7. - Also used in early-stage HCC as a **bridge to liver transplantation** or when liver transplantation, hepatic resection, and image-guided ablation are not possible. - Super-selective chemoembolization is recommended to increase treatment efficacy and minimize the ischemic insult to non-tumoral tissue. **Contraindications** - Macrovascular invasion of main portal branches or main portal vein - **Impaired portal vein blood flow (portal vein thrombus, hepatofugal blood flow) an absolute contraindication**. - Patients with biliary-enteric anastomosis or biliary stent are at higher risk of hepatic abscess, other treatments preferred. - **Doxorubicin (anthracycline) may induce cardiotoxicity in a dose-dependent chronic cardiomyopathy.** Left ventricular ejection fraction should be checked by ECHO in patients receiving multiple TACE sessions and the cumulative dose should not exceed 450 mg/m. **🔹 Why Does Post-TACE Syndrome (PTS) Happen?** **1) Tumor Ischemia & Necrosis** TACE blocks the arterial blood supply to the tumor. This leads to tumor necrosis, causing local inflammation. **2) Inflammatory & Cytokine Response** Necrotic tumor cells release pro-inflammatory cytokines (IL-6, TNF-α). This triggers systemic inflammatory symptoms like fever and malaise. **3) Toxic Chemotherapy Effects** Chemotherapeutic agents (e.g., Doxorubicin, Cisplatin) cause local hepatocyte damage. This leads to liver dysfunction and nausea/vomiting. **4) Hypoxia & Tissue Injury** Blocked blood flow causes hypoxia in surrounding liver tissue. Nearby healthy liver cells may suffer collateral damage, increasing AST/ALT levels **🔹 Prevention of Post-TACE Syndrome** 🔸**Optimizing TACE Techniques:** Super-selective embolization (minimizing damage to normal liver). Use of drug-eluting beads (DEB-TACE) (reduces systemic chemo exposure). 🔸**Pre- & Post-TACE Liver Support:** Good hydration & nutrition. Avoid hepatotoxic drugs (e.g., high-dose paracetamol, alcohol). 🔸**Pre-Procedural Medications:** Steroids (optional) to reduce inflammation. Prophylactic antibiotics in high-risk patients (diabetes, cirrhosis) ✅ PTS is common (~50–80% of TACE patients). ✅ It is self-limiting (resolves in ~5–7 days). ✅ Supportive care (fluids, pain control, antiemetics) is the main treatment. ✅ Persistent fever & worsening pain → Consider liver abscess or biloma.

Answer 13

nvolves transcatheter delivery of chemotherapy (Doxorubicin or Epirubicin, Cisplatin or Miriplatin) **emulsioned with Lipiodol**, followed by vascular stagnation achieved with particle embolization. - Better pharmacokinetic effect and long-term survival than injection of Lipiodol/drug emulsion without particles. - Common adverse events - liver enzyme abnormalities, fever, hematological/bone marrow toxicity, pain, and vomiting, related to **postembolization syndrome**.

Answer 14

**Selective Internal RT (SIRT) / Radioembolization** Infusion of radioactive 131-Iodine-labelled Lipiodol or resin or glass microspheres containing yttrium-90 (Y90) or similar agents into the hepatic artery which are preferentially delivered to the tumor-bearing area and selectively emit high-energy, low penetration ß-radiation to the tumor. **Contraindications** - Absolute - Lung shunting: Significant hepatopulmonary shunt >20%. - Relative - Compromised lung function, inadequate liver reserve & kidney function (Cr >2.0 mg/dL) & platelet < 75, portal vein thrombosis **Complications**: Post embolization syndrome. **Why is Lung Shunting a Contraindication for SIRT?** Selective Internal Radiation Therapy (SIRT), also known as radioembolization, uses **Yttrium-90 (Y-90)** microspheres to deliver targeted radiation to liver tumors. However, significant lung shunting can be a major contraindication due to the risk of radiation-induced lung injury. 🔹**What is Lung Shunting?** Lung shunting occurs when Y-90 microspheres bypass the liver and enter the pulmonary circulation via abnormal vascular connections between the liver and lungs. 🔹 **Why is Lung Shunting Dangerous in SIRT?** 1️⃣ Radiation Pneumonitis (RP) Y-90 delivers high-dose radiation to lung tissue. This can cause radiation pneumonitis, leading to cough, dyspnea, hypoxia, and fibrosis. 2️⃣ Pulmonary Fibrosis Chronic exposure to Y-90 radiation causes irreversible lung fibrosis. This can lead to respiratory failure over time. 3️⃣ Dose-Dependent Lung Toxicity Safe lung dose: <30 Gy Severe toxicity risk: >50 Gy If Lung Shunt Fraction (LSF) is too high, Y-90 dose adjustment is not enough to prevent toxicity.

Answer 15

- **Systemic therapy** should be offered to patients with preserved liver function (Child Turcotte-Pugh A or well-selected Child-Tur cotte-Pugh B cirrhosis), ECOG PS 0-1, who have **BCLC Stage C HCC**, or **BCLC Stage B HCC not amenable to or progressing after locoregional therapy** (Level 1, Strong Recommendation). - Patients with advanced HCC who have **Child-Turcotte-Pugh A cirrhosis should be offered atezolizumab plus bevacizumab(avastin) or durvalumab plus tremelimumab as preferred first-line therapy options**(Level 2, Strong Recommendation). - Patients with Child-Turcotte-Pugh A cirrhosis in **whom atezolizumab plus bevacizumab and durvalumab plus tremelimumab are contraindicated should be offered first line sorafenib or lenvatinib** (Level 1, Strong Recommendation).

Answer 16

- **Sorafenib** effective in first line. - Multikinase inhibitor: Inhibitor of Raf kinase, inhibitor of RAF, vascular endothelial growth factor receptor (VEGFR) - SHARP trial (Sorafenib HCC Assessment Randomized Protocol) shows survival benefit in late stage HCC. [DOI:10.1016/j.jhep.2012.06.014] - **Regorafenib** effective in second line in case of radiological progression under sorafenib. - **Lenvatinib** non-inferior to sorafenib in first line, but no effective second line option after Lenvatinib has been explored. * The adverse effect reported with systemic therapies are hand-foot skin reaction, hypertension, fatigue * No role of systemic chemotherapy as trials failed to demonstrate an increase in survival

Answer 17

In HCC on cirrhosis: - Acetaminophen ≤3 g/day to manage pain of mild intensity - NSAIDs should be avoided whenever possible in patients with underlying cirrhosis. - Opioids to manage pain of intermediate or severe intensity (proactively avoid constipation) Bone metastases causing pain or at significant risk of spontaneous secondary fracture benefit from palliative radiotherapy.

Answer 18

🔹**What is Hepatorenal Syndrome (HRS)?** Hepatorenal Syndrome (HRS) is a severe functional kidney failure that occurs in patients with advanced liver disease (cirrhosis, acute liver failure, or severe alcoholic hepatitis). It is caused by extreme renal vasoconstriction due to systemic circulatory dysfunction and splanchnic vasodilation. 🚨 Key Features: No structural kidney damage. Reversible if treated early. Poor prognosis without treatment (often requiring liver transplant). 🔹 **Pathophysiology of HRS** 1️⃣ **Portal Hypertension & Splanchnic Vasodilation** Cirrhosis and portal hypertension cause vasodilation in the splanchnic circulation (gut, spleen, pancreas). This leads to systemic hypotension. 2️⃣ **Activation of Vasoconstrictor Systems** The body compensates by activating RAAS (Renin-Angiotensin-Aldosterone System), Sympathetic Nervous System, and Vasopressin release. These mechanisms constrict renal arteries, reducing kidney perfusion. 3️⃣ **Severe Renal Hypoperfusion** The kidneys experience ischemia and low GFR, leading to functional kidney failure. Unlike acute kidney injury (AKI), there is no structural kidney damage. 🔹 **Management of HRS** 🚨**HRS Type 1 (Emergency Treatment)** 1️⃣ **Vasoconstrictors + Albumin (First-Line Treatment)** Terlipressin (preferred) OR Norepinephrine Albumin (1 g/kg IV on Day 1, then 40g/day) → Expands plasma volume. 2️⃣ **Liver Transplant (Definitive Treatment)** Best long-term option but limited by availability. 3️⃣**Dialysis (Temporary Support)** Used if severe electrolyte imbalances or acidosis. Does not improve survival without liver transplant. **✅ HRS Type 2 (Chronic but Progressive)** - Salt restriction + Diuretics (for ascites control). - Midodrine + Octreotide + Albumin (if hypotensive). - Liver transplant (definitive). 🔹**Prognosis of HRS** 🚨 Untreated HRS-1 → 80–90% mortality within weeks. ✅ Successful liver transplant → Best survival (>70% at 5 years)

Answer 19

🎯 **1. Milan Criteria (Established 1996 by mazzaferro – Gold Standard)** ✅ Eligibility: Single tumor ≤ 5 cm **OR** Up to 3 tumors, each ≤ 3 cm ❌ No macrovascular invasion ❌ No extrahepatic metastasis 📈 Outcome: ~75% 4-year survival ~85% recurrence-free survival 👉 Adopted by UNOS and most transplant centers globally 🏥 **2. UCSF Criteria (University of California, San Francisco – Expanded Criteria)** ✅ Eligibility: Single tumor ≤ 6.5 cm **OR** Up to 3 tumors, Largest ≤ 4.5 cm Total tumor diameter ≤ 8 cm ❌ No macrovascular invasion ❌ No extrahepatic disease 📈 Outcome: Comparable to Milan (~75% 5-year survival) Allows transplant for patients outside Milan but still within safe limits 🧮 Example 1 – Eligible (within UCSF): You have 3 tumors: Tumor 1: 3.0 cm Tumor 2: 2.5 cm Tumor 3: 2.0 cm Total = 3.0 + 2.5 + 2.0 = 7.5 cm ✅ Also, largest tumor ≤ 4.5 cm ✅ And total tumor diameter ≤ 8 cm ✅ → ✔️ This patient meets UCSF criteria 🔹 🧮 **3. Up-to-7 Criterion** – Definition: Sum of: ✅ Number of tumors + ✅ Diameter (in cm) of the largest tumor ➡️ Must be ≤ 7

Hepatocellular Carcinoma ( HCC) Flashcards

(44 cards)