Approach to liver nodules.pptx

1. Approach to liver Mass By: Dr. Rebil Heiru (Year III IM Resident) Moderator: Dr. Fikadu Girma (Internist, Gastroenterologist and Hepatologist) May,2021 ADAMA HOSPITAL MEDICAL COLLEGE

2. Outline • Introduction • General approach • Malignant liver masses • Benign liver masses • Hepatic cysts

3. Introduction • Hepatic mass lesions include tumors, tumor-like lesions, abscesses, cysts, hematomas, and confluent granulomas. • Hepatic tumors can be primary (from hepatocytes, bile duct epithelium, or from mesenchymal tissue) or secondary. • In adults in most parts of the world, hepatic metastases > 10 malignant tumors of the liver • In children, 10 malignant tumors > both metastases and benign tumors of the liver. • Except for cavernous hemangiomas, benign hepatic tumors are rare in all geographic regions and in all age groups.

4. General approach HX • Age • Gender • Travel history • OCP, anabolic steroid use • Previous imaging • Comorbid illness • Pain • Hx of underlying liver dxs • Recent IDA, DM PE • Stigmata’s of CLD • Hepatomegally • Palpable mass • Bruit • Pallor • Jaundice • Peripheral edema

5. lab • CBC • AST, ALT, ALP, Bilirubin • Viral markers • Iron levels • CEA, CA 19-9, AFP • LDH • Urine 24 hr 5 HIAA

6. Malignant Tumors

7. HCC Epidemiology • HCC is the most common primary malignant tumor of the liver (90%)- 7% of all cancers • It is the fifth most common cancer in men and the eighth most common in women • Ranks fourth in annual cancer mortality rates. • Men>women 3.7:1 to 2.4:1 • Old Age, highest among 70-79yrs

8. HCC Epidemiology…. • Liver cancer incidence/mortality is increasing worldwide (WHO 1M deaths in 2030) • Highest increase in incidence in US among all tumor types • Etiological landscape is changing (↑ in NAFLD↓viral hepatitis) • Rare among children

11. Risk Factors

15. DIAGNOSIS • Serum Tumor Markers • AFP • Fucosylated AFP • Des-γ-Carboxy Prothrombin • The roles in the diagnosis of HCC for markers such as glypican-3 (GPC3), Golgi protein 73, hepatocyte growth factor, IGF 1, and transforming growth factor-β1 await further study.

16. Imaging • U/S • CT • MRI • PET • Hepatic angiography • Laparascopy

17. Imaging • Classic HCC …CT or MR imaging is a mass that shows 1. APHE 2. subsequent washout during PVP or more delayed images, and 3. delayed capsular or pseudocapsular enhancement • When present, these 3 major features allow HCC to be treated without the need for biopsy confirmation • Tumor thrombus may show arterial phase enhancement • CT sensitivity 67.5% Specificity 92.5% • MRI sensitivity 80.6% and specificity 84.8%

21. • If these criteria are not present but HCC or other malignancy is considered probable, then a liver biopsy should be considered for diagnosis. Diagnosis of HCC cannot be made by imaging in patients without cirrhosis, even if enhancement and washout are present, and biopsy is required in these cases. • Histological markers gpC3, HSp70, and GS can be assessed to distinguish high-grade dysplasia from HCC on histology if HCC cannot be diagnosed based on routine histology.

23. • Pathology • Gross appearance • Nodular • Massive • Diffusely infiltrating • Microscopic appearance • Well differentiated • Moderately differentiated • Undifferentiated • Progenitor cell HCC

24. • Metastases • Autopsy (40-57%) • Lungs 50%, LNs 20%...adrenal glands • Fibrolamellar HCC • Young • M=F • Doesn’t secrete AFP • Not caused by CHBV/CHCV • Non cirrhotic liver • Amenable to surgical Rx… good prognosis • Mixed type… poor prognosis

25. Staging • TNM (doesn’t account the underlying liver dxs) • Okuda, • Cancer of the Liver Italian Program, • Barcelona Clinic Liver Cancer (BCLC), • Chinese University Prognostic Index, • Japanese Integrated Staging, and • Group d’Etude et Traitement du Carcinome Hépatocellulaire

28.  Definitive dx requires histologic correlation Immunostaining GPC3 Heat shock protein 70 (HSP70) Glutamine synthetase Gene expression profiling GPC3 LYVE1 [encoding lymphatic vessel endothelial hyaluronan receptor-1], BIRC5 [encoding baculoviral inhibitor of apoptosis repeat-containing-5, or survivin

29.  The main clinical prognostic factors in patients with HCC: Number and size of nodules Presence of vascular invasion Extrahepatic spread Liver function (defined by Child-Pugh’s class) General tumour-related health status [ECOG]

30. •Unlike most solid tumours, the co-existence of two life-threatening conditions, such as cancer and cirrhosis complicates prognostic assessments. •HCC has a poor prognosis when diagnosed after the onset of symptoms (0-10% 5-year survival rate).

31. Treatment •There have been significant advances in HCC treatment over the past 10 years, with improvements in both technology and patient selection. •Available therapeutic options can be divided into curative and noncurative interventions.

32. Treatment • Surgical resection • LT • Local ablation • Chemoembolization • Chemotherapy • Alternative techniques and combinations • Cryoablation • Laser ablation • External beam radiation • Y-90 • Sorafenib + TACE

33. Treatment… Treatment of HCC Curative resection OLT Ablation Noncurative TACE TARE SBRT Systemic chemotherapy

35. Treatment

38. Treatment of HCC: liver resection EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Surgery is the mainstay of HCC treatment • Best outcomes of any treatment in well-selected candidates • 5-year survival of 6080% • Liver resection and transplantation is first option with early tumours • Extended to other stages after non-surgical tumour downstaging Recommendations Surgical resection is the treatment of choice in patients with HCC arising on a non-cirrhotic liver Low Strong Indications for resection of HCC in cirrhosis should be based on: • Multi-parametric composite assessment of liver function • Portal hypertension • Extent of hepatectomy and expected volume of future liver remnant • Performance status • Patient co-morbidities High Strong Peri-resection mortality in cirrhotic patients should be <3% High Strong Level of evidence Grade of recommendation

39. Assessment of post-resection risk of hepatic decompensation EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Multi-parametric assessment • Risk of decompensation based on three determinants of liver insufficiency • Portal hypertension • Extent of resection • Liver function • Likelihood of decompensation • High: >30% • Intermediate: <30% • Low: 5%

40. Extent of resection: anatomical vs. non- anatomical Residual region of tumour- bearing 3rd-order portal branch at high risk of tumour recurrence A Anatomical resection (A-A’) removes entirely the tumour-bearing portal branches bordered by the landmark veins, while non-anatomical resection (B-B’) is any other type of resection in which the tumour- bearing 3rd-order portal region is not fully removed B After non-anatomical resection of HCC some part of the tumour-bearing portal region is left, which is at high risk of tumour recurrence

41. Liver resection and tumour parameters EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Indications and choice of surgical technique depend on tumour size and location(s) Recommendations Liver resection is recommended for single HCC of any size • In particular, for tumours >2 cm when hepatic function is preserved and sufficient remnant liver volume is maintained Moderate Strong In properly trained centres, liver resection should be considered via laparoscopic/minimally invasive approaches, especially for tumours in anterolateral and superficial locations Moderate Weak HCC presenting with two or three nodules within Milan criteria may be eligible for liver resection depending on: • Performance status • Co-morbidities • Preservation of liver function and remnant volume Low Weak Level of evidence Grade of recommendation

42. Minimally invasive/laparoscopic resection for HCC EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Laparoscopic-robotic resection for HCC located in superficial- peripheral positions of the liver provides optimal survival outcomes • While minimizing complications and hospital stay Scan detection of liver tumour Laparoscopic treatment of the affected organ through small openings Removal of affected region Minimal signs of invasive surgery and rapid patient recovery

43. Liver resection contraindications and follow- up • A substantial proportion of patients with HCC present with tumour-related portal vein thrombosis • Disease at advanced stage and not amenable to curative treatment • Tumour recurrence complicates 70% of cases at 5 years Recommendations • HCC-related macrovascular invasion is a contraindication for liver resection • Intervention on distal portal invasion – at segmental or sub-segmental level – deserves investigations within prospectively designed protocols Moderate Neoadjuvant or adjuvant therapies are not recommended because they have not been proven to improve the outcome of patients treated with resection High Strong Follow-up* after resection with curative intent is recommended because of high rates of treatable recurrence High Strong Level of evidence Grade of recommendation

44. Treatment of HCC: LT • Together with NAFLD/NASH, HCC is the fastest growing indication for LT • Milan criteria are the benchmark for selecting patients for LT • Basis for comparison with other suggested criteria Recommendations LT is recommended as the first-line option for HCC within Milan criteria but unsuitable for resection High Strong Consensus on expanded criteria for LT in HCC has not been reached Patients outside Milan criteria can be considered for LT after successful downstaging to within Milan criteria, within defined protocols Moderate Weak Tumour vascular invasion and extrahepatic metastases are an absolute contraindication for LT in HCC High Level of evidence Grade of recommendation

46. Local ablation and external radiation • Tumour ablation techniques have improved along with the imaging-guidance tools required to ensure their successful application Recommendations Thermal ablation with radiofrequency is the standard of care for patients with BCLC-0 and A tumours not suitable for surgery* High Strong In patients with very early stage HCC (BCLC-0) radiofrequency ablation in favourable locations can be adopted as first-line therapy even in surgical patients Moderate Strong Microwave ablation showed promising results for local control and survival Low Ethanol injection is an option in some cases where thermal ablation is not technically feasible, especially in tumours <2 cm High Strong External beam radiotherapy is under investigation • So far there is no robust evidence to support this therapeutic approach in the management of HCC Low Weak Level of evidence Grade of recommendation

47. Percutaneous ablation • Thermal injury of adjacent structure • Heat sink effect (near major vessels) • Multibipolar mode is less sensitive to heat sink effect Advantag es Limitatio ns • Well-evaluated treatment (reference) • Multibipolar mode: increases volume and predictability (margin) of ablation zone • No reliable endpoint to set the amount of energy deposition • Higher and faster temperature picks reached than with RFA (less sensitive to heat sink effect than monopolar RFA) • Limited risk of thermal injury to neighbouring critical structures • Unsensitive to heat sink effect • Advantage of multibipolar mode (no touch technique, predictability of margins) • Cryoshock with first device • Limited clinical data available with new devices • Easy monitoring with imaging of ice ball progression • Only preliminary clinical data • General anaesthesia using curare and major analgesic drugs is mandatory Radiofrequency ablation Microwave ablation Cryoablation Irreversible electroporation Monopolar RFA Multibipolar No touch RFA Active energy deposition: few mm Active energy deposition: ~1 cm Ice ball: ~1–3 cm Cell membran e

48. Transarterial therapies EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Benefits of TACE in appropriately selected patients have been robustly demonstrated Recommendations TACE is recommended for patients with BCLC stage B and should be carried out in a selective manner High Strong The use of drug-eluting beads has shown similar benefit to conventional TACE and either of the two can be utilized High Strong TACE should not be used in patients with: • Decompensated liver disease • Advanced liver and/or kidney dysfunction • Macroscopic vascular invasion • Extrahepatic spread High Strong Level of evidence Grade of recommendation

49. First line systemic treatments

50. First-line systemic therapies EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • VEGFR and multi-kinase inhibitors have shown survival benefits in advanced HCC • First line: sorafenib and lenvatinib Recommendations Sorafenib is the standard first-line systemic therapy for HCC, indicated for patients with: • Well-preserved liver function (Child–Pugh A) and with advanced tumours (BCLC-C) • Earlier stage tumours progressing upon, or unsuitable for, loco-regional therapies High Strong Lenvatinib is non-inferior to sorafenib and is also recommended in first-line therapy for patients with: • Well-preserved liver function, good performance status and advanced tumours (BCLC-C) without main portal vein invasion • Tumours progressing with, or unsuitable for, loco-regional therapies High Strong Level of evidence Grade of recommendation

51. Non-inferiority results in advanced HCC EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019

52. Lenvatinib vs Sorafenib

53. Second line systemic therapies

54. Cabozantinib vs placebo (CELESTIAL)

55. Ramuricumab vs Placebo (REACH)

56. Second-line systemic therapies *In patients with high baseline alpha-fetoprotein (> 400 ng/ml) EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • VEGFR and multi-kinase inhibitors have shown survival benefits in advanced HCC • First line: sorafenib and lenvatinib • Second line: regorafenib (and cabozantinib and ramucirumab*) • Another agent that has shown some promise is the checkpoint inhibitor nivolumab Recommendations Regorafenib is recommended as second-line treatment for patients: • Tolerating and progressing on sorafenib • With well-preserved liver function (Child–Pugh class A) • With good performance status High Strong Cabozantinib and ramucirumab* have shown survival benefits vs. placebo in this setting - - Based on uncontrolled but promising data, immune therapy with nivolumab has received FDA approval in second-line treatment, pending Phase 3 data for conventional approval • At present, the data are not mature enough to give a clear recommendation Moderate Weak Level of evidence Grade of recommendation

58. Systemic therapies in development EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Other systemic treatments are in development • Have not yet demonstrated non-inferiority or clinical benefit • Further clinical trials are required Recommendations • Treatments that failed to meet their endpoints in randomized trials are not recommended • Further clinical trials are needed to confirm claims of non-inferiority, or any trends of better outcome identified in subgroup analysis High • Patients at BCLC D stage, who are not LT candidates, should receive palliative support, including management of pain, nutrition and psychological support • In general, they should not be considered for clinical trials Low Strong Level of evidence Grade of recommendation

59. Overview of EASL recommendations for treatment EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • *Other molecular therapies: sunitinib, linifanib, brivanib, tivantinig, erlotinib, everolimus • Weak recommendation: more evidence needed

60. Palliative and best supportive care EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019 • Management of end-stage disease is only symptomatic • No tumour-directed treatment is indicated • Psychological burden of end-stage HCC should not be neglected or underestimated Recommendations 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) Low Weak Bone metastases causing pain, or at significant risk of spontaneous secondary fracture, benefit from palliative radiotherapy Low Level of evidence Grade of recommendation

61. Surveillance

62. Hepatic Metastases  The liver is the most frequent target for metastatic spread of tumors • 40% - 50% of adult patients with extrahepatic primary malignancies. • Double blood supply of the liver and fenestrations in the sinusoidal endothelium

63. • Metastatic disease of the liver is seen much more commonly than the occurrence of primary hepatic malignancies • Metastatic disease of liver is 30X > primary liver malignancy. • Most often identified as multiple masses, but also can present as a solitary or larger confluent mass

64. • Hepatic metastases commonly originate from primary sites in the distribution of the portal venous system, including the pancreas, stomach, and colon. • Outside this distribution, tumors of the lung and breast are the most common origins of hepatic metastases.

65. Clinical features • Usually masked by the primary malignancy • If 10 is asymptomatic… malaise, weight loss, upper abdominal pain and jaundice • Hepatomegaly, irregular borders and umblicated nodules • Friction rub

67. Hypovascular Metastasis • Colon, lung, prostate, gastric, and bladder carcinomas • PVP as hypoenhanced masses relative to the adjacent liver and can also show delayed enhancement Hypervascular metastasis: • NE tumor, RCC, melanoma(ocular), sarcoma, and thyroid ca • U/S ->hypoechoic halo, central calcification Wash out • T2 hyperintense on MR imaging

69. Treatment and Prognosis • The extent of replacement of liver tissue by metastases generally determines the patient’s prognosis. • Approximately 50% of patients surviving 3 months after the onset of symptoms and <10% surviving >1yr • Survival for 5 years can be achieved in up to 60% who undergo resection of a solitary colon cancer metastasis to the liver

70. • Long-term survival has been accomplished most often by resection of hepatic metastases in patients with colorectal cancer • Substantial number of whom have been cured or have obtained up to 20 years of disease-free survival.

71. • If the primary tumor has been removed completely and metastases are confined to the liver, resection of hepatic metastases should be considered • Liver transplantation, with or without chemotherapy, has been limited to a few patients • RFA is a valid therapy for colorectal metastases in patients who are unable to tolerate or refuse surgical resection.

72. Intrahepatic Cholangiocarcinoma • Cholangiocarcinoma (CCA) is classified according to its anatomic location as: • Intrahepatic (iCCA; ~30%) • Perihilar (pCCA; ~50%) and • Distal (dCCA: ~20%) • The latter two are also known as extrahepatic cholangiocarcinomas (eCCA)

73. • ICCA represents approximately 10% to 20% of all primary liver cancers and 20% of cholangiocarcinoma • The M:F ratio is 1.5:1 • Asymptomatic until the tumor is advanced • The clinical features are then similar to those of HCC • 165% increase between the late 1970s and the late 1990s

74. Etiology and Risk Factors • The strongest association is with Opisthorchis viverrine liver fluke acquired by ingestion of raw or uncooked fish • Clonorchis sinensis (weak association), thorotrast (thorium dioxide) • Congenital and acquired abnormalities of the biliary tract (biliary atresia, choledochal cysts, hepatholithiasis)→ bile stasis, chronic inflammation, and infection • PSC, cirrhosis, smoking, alcohol, DM

75. DIAGNOSIS • CA 19-9 is the most frequently used serum tumor marker for cholangiocarcinoma but has significant limitations • CA 19-9 levels are also elevated in pancreatic, colorectal, gastric, and gynecologic cancers and in acute bacterial cholangitis • In patients with unexplained biliary obstruction without PSC, the sensitivity of CA 19-9 is 53%, and the negative predictive value is 72% to 92%, for a cutoff value of 100 U/mL. • Often only the serum ALP level is elevated.

76. Imaging • progressive enhancement in arterial, portal venous, and delayed phases, thereby helping to distinguish it from HCC, which usually has washout in the later 2 phases. • Other associated findings may include hepatic capsular retraction, vascular encasement that may lead to lobar atrophy, and dilatation of peripheral bile ducts. • MRCP: site of obstruction and extent of biliary tree involvement • 5 yr survival <5%

79. Hepatic haemangiomas: epidemiology • Most common primary liver tumours • Prevalence on imaging series: ~5% • Prevalence on autopsy series: up to 20% • Most common in women aged 30–50 years • Female to male ratio ranges from 1.2–6:1 • Can occur in all age groups

80. Hepatic haemangiomas: clinical characteristics • Rarely of clinical significance • Often solitary and small (<4 cm), although can reach 20 cm in diameter • Most patients are asymptomatic even with large haemangiomas • Larger tumours (>10 cm) may be symptomatic – associated with pain and features of KMS (inflammatory reaction syndrome and coagulopathy)

81. Hepatic haemangiomas • Classic appearance on US… US is sufficient for dx! Homogenous hyperechoic mass <3cm Acoustic enhancement Sharp margins Lack of halo sign • MRI 90% • Needle biopsy 96% • A hyperechoic mass in a healthy liver  suspect hemangioma

82. Hemangioma A, Hemangioma. Ultrasonography demonstrates a large circumscribed uniformly hyperechoic mass in the right hepatic lobe B, Ultrasonography demonstrates atypical hypoechoic appearance of a large hemangioma (in the setting of an echogenic liver due to hepatic steatosis).

83. Hepatic haemangiomas: imaging EASL CPG benign liver tumours. J Hepatol 2016;65:386–98 T2 T1 CE Typical haemangioma adjacent to FNH MRI CEUS CE CE Strongly hyperintense Hypointense Lesion shows peripheral and discontinuous enhancement followed by complete fill-in on delayed-phase imaging

84. Hepatic haemangiomas: key diagnostic recommendations Recommendations Contrast enhanced imaging (CEUS, CT or MRI) is required in oncology patients and patients with underlying liver disease II-2 1 Diagnosis by contrast-enhanced imaging is based on a typical vascular profile, characterized by peripheral and globular enhancement on arterial phase followed by a central enhancement on delayed phases MRI provides additional findings: e.g lesion signal on T1-, T2- weighted sequences; diffusion imaging II-2 1 Grade of evidence Grade of recommendation

85. Hepatic Hemangiomas Atypical hemangiomas • Rapidly filling • strong hyper intensity on T2-weighted images • enhancement concomitant with that of arterial structures and • persistent enhancement on delayed phase imaging • Giant hemangiomas • may show central heterogeneity related to thrombosis or fibrosis • Other atypical haemangiomas are very uncommon and include those that have very slow filling and calcified or hyalinized haemangiomas (also called sclerosing haemangiomas).

86. Hepatic haemangiomas… • Haemangiomas are mostly asymptomatic incidental discoveries • May change in size during long-term follow-up • No relationship between size and complications • Little relationship between symptoms and characteristics • Benefit of surgery debatable

87. Hepatic haemangiomas: key management recommendations Recommendations Due to its benign course, imaging follow-up is not required for typical haemangioma II-2 1 Pregnancy and OCPs are not contraindicated III 2 Conservative management is appropriate for typical cases II-2 1 Refer to benign liver tumour MDT in the presence of KMS, growing lesions or lesions that are symptomatic by compression III 1 Grade of evidence Grade of recommendation

88. FNH: epidemiology • Clinically relevant prevalence: 0.03% • autopsy series: 0.4–3% • Up to 90% of patients are female • Average age at presentation: 35–50 years

89. FNH: clinical characteristics • Most cases are solitary and <5 cm; multiple FNH in 20–30% of cases • Hyperplastic hepatocellular lesions resulting from arterial malformation • Size is stable over time in most cases • Most cases are asymptomatic and complications are extremely rare

90. FNH: imaging • Usually associates several findings 1. Lesion homogeneity, excluding the central scar 2. Slight difference from adjacent liver tissue on pre-contrast US, CT and MRI 3. Strong, homogeneous enhancement on arterial phase CEUS, CT or MRI with a central vascular supply; becomes isointense to liver tissue on portal venous and delayed phases 4. Central scar best seen on MRI 5. Lack of capsule with often lobulated contours

95. FNH: key diagnostic recommendations • MRI sensitivity • Lesion >3 cm – very good • Lesion <3 cm – second imaging modality advised, such as CEUS • Refer to a specialist centre if in doubt with two imaging modalities Recommendations CEUS, CT, MRI: nearly 100% specificity with a combination of typical imaging features II-2 1 MRI has the highest diagnostic performance overall Highest diagnostic accuracy by CEUS is achieved in FNH <3 cm II-2 1 Grade of evidence Grade of recommendation

96. FNH: key management recommendations • In the absence of symptoms a conservative management approach is recommended • No indication for discontinuing OCPs • Follow-up during pregnancy is not necessary Recommendations For a typical FNH lesion, follow-up is not necessary unless there is underlying vascular liver disease III 2 Treatment is not recommended II-3 2 If imaging is atypical, or the patient is symptomatic, refer to a benign liver tumour MDT III 1 Grade of evidence Grade of recommendation

97. FNH: management algorithm Suspected FNH Contrast-enhanced imaging (preferably MRI)* Diagnosis FNH certain Diagnosis FNH doubtful Discharge, no follow-up needed Confirmed FNH Biopsy CEUS <3 cm >3 cm Diagnosis uncertain Map-like pattern of GS is specific to FNH GS immunohistochemical staining is useful in difficult cases

98. HCA: epidemiology/clinical characteristics • Epidemiology • Reported prevalence: 0.001–0.004% • ~10x less common than FNH • Most common in women (10:1 female to male), especially aged 35–40 years • Potential role of sex hormones • 30–40-fold increase in incidence with long-term OCP use • Incidence among males is associated with androgenic steroids

99. HCA: epidemiology/clinical characteristics • Recent increase in prevalence associated with rising obesity and metabolic syndrome • Significant risk of haemorrhage and malignant transformation • Especially with lesions ≥5 cm HCAs need to be followed more closely than other benign tumours!

100. HCA: molecular classification • Molecular subtype is highly associated with risk of transformation to HCC β-HCAs exhibit the highest risk of malignancy; men are at a higher risk of malignancy

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104. HCA: key diagnostic recommendations • Imaging features reflect the tumour molecular subtype • Imaging should be fat sensitive and use contrast agents to look for dilated vascular spaces • EASL CPG benign liver tumours. J Hepatol 2016;65:386–98 Recommendations MRI is superior to all other imaging modalities Due to its intrinsic properties to detect fat and vascular spaces it offers the opportunity to subtype HCA up to 80% II-2 1 MRI has >90% specificity for positive identification of HNF-1α or inflammatory HCA Identification of β-catenin-activated HCA and distinction from unclassified HCA or HCC is not possible with any current imaging technique II-2 1 Grade of evidence Grade of recommendation

105. HCA: key management recommendations • HCAs have the potential for haemorrhage or malignant transformation • Management should involve a benign liver tumour MDT • EASL CPG benign liver tumours. J Hepatol 2016;65:386–98 Recommendations Base treatment decisions on sex, size and pattern of progression III 2 Discontinuation of OCPs and weight loss should be advised II-2 1 Resection irrespective of size is recommended in men and in all cases of proven β-catenin mutation II-3 2 Observe women for 6 months after lifestyle change. • Resection is indicated with lesions ≥5 cm and those continuing to grow • Reassess lesions <5 cm at 1 year with annual imaging thereafter II-3 II-3 III 2 2 2 Bleeding HCAs with haemodynamic instability should be embolized and a residual viable lesion on follow-up imaging is an indication for resection III 2 Grade of evidence Grade of recommendation

107. HCA and Pregnancy • Requires close follow up (6-12wks U/S) • Follow size •  in size and associated  risk of rupture…involve obstetrician • HCA <5cm, no evidence of growth or not exophytic mass…no evidence for C/S… vaginal delivery can be pursued • Surgery is preferrable than IR • If HCA located peripherally, small and before 24 wks • EASL CPG benign liver tumours. J Hepatol 2016;65:386–98

108. Hepatic Cysts •Hepatic cysts are abnormal fluid-filled spaces in the hepatic parenchyma and biliary tree. 3 main types: Fibrocystic diseases of the liver Cystadenomas and cystadenocarcinomas Hydatid cysts

109. •Fibrocystic diseases of the liver •originate from abnormal persistence or defects in the progressive remodeling of the ductal plate during development, resulting in dilated fluid filled spaces, including •hepatic and choledochal cysts, •portal fibrosis, and ductal plate malformations

110. •Fibrocystic disorders of the liver include Simple hepatic cysts PCLD Fibrocystic disease associated with autosomal recessive polycystic kidney disease Von myenburg complexes Carolis disease

111. Simple Cysts • Simple hepatic cysts are thought to be congenital in origin and have a frequency of about 2.5% of the population. • Usually smaller than 5 cm in diameter • If >3 considered part of PCLD • Asymptomatic and discovered incidentally during upper abdominal imaging

112. •They occur more often in women than in men, •Prevalence increases with age. •When symptomatic, they can produce complications including intracystic bleeding, infection, rupture, or compression of adjacent organs. •RX: percutaneous drainage or sclerosing (doxy)

113. Polycystic Liver Disease • PCLD is a rare condition in which multiple cysts form in the hepatic parenchyma • PCLD usually presents in association with ADPKD • Cysts range in diameter from a few millimeters to 10 cm or more. • They contain clear, colorless, or straw-colored fluid

114. • The cysts usually are asymptomatic and discovered incidentally during upper abdominal imaging. • Symptoms occur in patients with more numerous and larger cysts (10% to 15% of patients, usually women), generally with markedly enlarged livers.

115. • Protuberant abdomen • Inability to bend over, and shortness of breath • Severe pain: rupture or infection of a cyst, bleeding into a cyst, or torsion of a pedunculated cyst • Jaundice is evident in approximately 5% of patients • Ascites: is the result of portal hypertension

120. Mgt Open surgical cyst fenestration (deroofing or marsupialization) leaves the cysts open to drain into the peritoneal cavity successful in up to 90 % of cases

121. ECHINOCOCCAL CYST • Echinococcal (hydatid) cysts of the liver are caused by the larval form of Echinococcus granulosus • Usually acquired from infected dogs. • These are fluid-filled structures limited by a parasite-derived membrane, which contains germinal epithelium.

122. Treatment • Treatment of hydatid disease usually involves anthelminthic therapy combined with either surgical resection of the cyst or percutaneous aspiration • Albendazole is highly effective

123. References • Sleisenger and Fordtran's Gastrointestinal and Liver disease, 11th edition. • UpToDate • EASL-CPG-on-Management-of-benign-liver-tumours • EASL-CPG-Management-of-hepatocellular-carcinoma • AASLD guideline for the management of HCC • Radeopedia.org

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