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Disclosures Liver Lesions: How to Evaluate? · 2020. 2. 10. · • Bright on T2-weighted images is...
Transcript of Disclosures Liver Lesions: How to Evaluate? · 2020. 2. 10. · • Bright on T2-weighted images is...
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Liver Lesions: How to Evaluate?
Laura Kulik MD
Professor of Medicine, Surgery and Interventional Radiology
Northwestern University Finberg School of Medicine
Disclosures
• Consulting: BMS, Bayer, BTG, Eisai
Malignant Lesions
• Hepatocellular Carcinoma (HCC)
• Intrahepatic Cholangiocarcinoma (ICCA)
• Metastatic lesions
• Hepatic Angiosarcoma
• Hepatic Epithelioid Hemangioendothelioma
(HEHE)
Cirrhosis
Unrelated to Cirrhosis
Burden of Hepatocellular Carcinoma • Increased incidence
• Peak incidence of HCV induced HCC in 2020
• In US rising faster than all other cancer except lung cancer
• Main cause of death in patients with cirrhosis
– 1/3 of cirrhotic pts. develop HCC over their lifetime
• HCC is the indication for OLT in 15-50% of centers
• DM is an independent risk factor for HCC– Males with BMI > 40 have a 5x increased mortality
• Novel therapies are needed to treat HCC at various stages
– 5-yr cause specific HCC survival: 3% 1975-1977 vs. 18%1998-2007
– Attributed to diagnosis and treatment at earlier stage
• 5-yr. OS: Localized 31% vs. 3% in metastatic
Parkin DM et al. Int J Cancer 1999;80:827-41. World Health Organization; Sangiovanni A et al. Hepatology. 2006;43(6):1303-10;
El-Serag HB et al. N Engl J Med 1999;340:745-50; Calle EE. NEJM 2003;348:1625-38.Altekruse SF et al. Hepatology 2012;55:476-82
www.cancer.org/cancer ; www.wcrf.org/cancer_statistics/world_cancer_statistics.php.
Risk of HCC• Inflammation leading to scar tissue
• Prospective study identified risk for HCC:
– Platelet < 75,000
– > 55 y/o
– + HCV
– PT > 75% baseline
5 year risk of HCC:
HCV cirrhosis 17% West; 30% East
Hemochromatosis 21%
HBV cirrhosis 10% West; 15% East
ETOH cirrhosis 8 -12%
Biliary cirrhosis 4%
Liver stiffness α with risk of HCC
El Serag et al Hepatology 2014 Singh S et al Clin Gastroenterol Hepatol 2013 2013 ;11(12):1573-84.
Velazquez RF et al. Hepatology 2003;37:520-7.
Diagnosis of HCCIn Cirrhosis
Arterial Enhancement Venous Washout
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Alteration in Blood Supply in HCC
Andreana L. et al World J Hepatol. 2009 October 31; 1(1): 48-61.
Small HCC may be Hypovascular:• 38% of 1-2 cm Bx proven
HCC did not meet radiographic criteria with lack of arterial enhancement
Bolondi L et al Hepatology 2005;42(1):27-34
Diagnosis of HCC
< 1 cm > 1 cm
*4 phase CT/contrast enhanced MRIarterial hypervascuarity
AND venous or delayed phase washout
YES
Low likelihood of HCCUS q 3 months
No growth up to 2 yrs.Resume q 6 month US
HCC
NO
Characteristic on other contrast
enhanced study
NOBiopsyIf neg, cont. to follow q 3-6 mo, consider repeat BX
“Because performance of the study is so crucial to non-invasive diagnosis of HCC, it is
recommended that these studies be performed in expert centers”.
Bruix J et al. Hepatology 2011;53: 1020-22.
LI-RADS: Liver Imaging Reporting and Data System
Increased contrast enhancement on LATE arterial images
AND
Washout on portal venous phase
AND/OR
Pseudocapsule enhancement
OR
Increased contrast enhancement on LATE arterial images
AND
Growth of ≥ 50% on serial CT or MRI obtained ≤ 6 months apart
IL1 BENIGNL2 PROBABLY BENIGNL3 INTERMEDIATEL4 PROBABLE HCCL5 DEFINITIVE HCC
Mitchell DG. et al. Hepatology 2015;61:1056-65.
5A = ≥ 1 cm & < 2 cm5B = ≥ 2 cm & ≤ 5 cm
Ancillary Imaging Features
Mosaic Architecture
Purysko AS et al. Radiographics 2012;32:1977-95.
*Discrete ring along the lesion, margin that is thicker or of greater conspicuity than the ring along the margin of regenerative nodules✚Includes nodule in nodule
Arterial Venous
Is a Liver Biopsy Needed?
• Risk of needle track seeding– Reported rates vary: 3 – 9%
• Variation based on– Diameter of needle– # of passes– Amount of normal liver parenchyma transversed– FNA reported less than tru cut needle
• Meta- Analysis of 8 studies, all published prior to 2007– Overall incidence 2.7% (95% CI 0.018 – 0.040)
• Median time to seeding 17 months– N= 26 confirmed needle tract seeding, none impacted OS
• All treated with resection or ablation; none had OLT
• Risk of false negative continue imaging to monitor
Chhieng DC et al. World J Surg Oncol 2004;2:5. Silva MA et al. Gut 2008;57:1592‐96.
Milan Criteria
• No evidence of VI/mets
– Based on pre-transplant imaging
– 4 year survival : 74%
– Recurrence rate: <10%
– Studies with > 1000 Validated in several patients
• 5 yr survival: >70%• Recurrence: < 15%
– International registry: 5 yr OS 902 pts s/p OLT
• 1983- 1990: 23.5%• 1991-1996: 44.4%• 1997 – 2005: 67.8%
Mazzoferro et al N Engl J Med 1996;334(11):693-9. Onaca N. et al. Liver Transpl. 2009 Jun;15(6):574-80.
3 lesions, none > 3 cm
1 lesion < 5 cm
S. Cook ‘97
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Listing for Liver Transplant
HCC MELD Upgrade:
OLD NEW as of 10/08/15
Initial Score 22 Calculated MELD Score
Extension 1 25 Calculated MELD score
Extension 2 28 28
Extension 3 29 30
Extension 4 31 31
Extension 5 33 33
Extension 6+ 35 Cap of 34
6 mo. Waiting until HCC MELD upgrade applies
Native MELD-Na: 6-40
Limited Resource
End stage Liver disease HCC patients
Waiting list for liver transplant: 15,000-16,000
Liver transplants in 2016: 7841
Post Transplant Outcomes
DAAs Reduce Incident HCC
Kanwal et al. Gastroenterology 2017Kanwal et al. Gastroenterology 2017
Intrahepatic Cholangiocarcinoma• Poor outcomes
– 5-yr. OS < 5%– Increase in Incidence worldwide
• age-adjusted 0.32 per 100,000 to 0.85 per 100,000 over 30 yrs.
• Risk factor: Chronic biliary stasis/inflammation– PSC (present at younger age)– Intrahepatic stones– Liver flukes– HCV/HBV– Cirrhosis– Chemical exposure: thorium dioxide, dioxin, asbestos, and radon. – Congenital abnormalities of bile ducts (Caroli’s, choledochal cysts)– DM– ETOH/smoking
• Distinction between iCCA and HCC needed– Poor prognosis w/ ICCA w/ high recurrence rates
• Can distinguish from HCC on imaging
• No MELD upgrade due to reduced OS c/w HCC in OLT
16Rimola et al Hepatology 2009;50:791-798. Rana A et al. Curr Opin Gastroenterol.2012 May;28(3):258-65.
Hepatic Abscess• Most pyogenic: portal or biliary origin
• More common in right lobe, majority solitary
• Risk factors: DM, cirrhosis, immunocompromised, advanced age, PPI
• Imaging characteristics variable depending on stage of disease
• Can mimic a solid mass– Rim- like enhancement with central
non-enhancing area– Can have no non-enhancing areas– -Transient enhancement on arterial – PVT or HV thrombosis
• Clinical signs of infection are key: fever, chills, RUQ pain
• -50% + Blood culture
Mavilla MG et al. J of Clin Transplational Hepatol. 2016;4:158-68.
Benign Lesions in Cirrhosis
*Arterial phase nonhyperenhancing atypical nodules may be categorized as LR-2 at the discretion of the radiologist.
“Teaching Point: Note that hepatocellular adenoma and focal nodular hyperplasia, both of which are benign and are usually hyperenhancing during the arte- rial phase, are purposely omitted from the pro- vided list of differential diagnoses for LR-1 and LR-2, since these conditions rarely occur in cirrhotic livers”
Purysko AS. Radiographics 2012;:1977-95.
L1 BENIGNL2 PROBABLY BENIGNL3 INTERMEDIATEL4 PROBABLE HCCL5 DEFINITIVE HCC
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Benign Lesions in Cirrhosis
Confluent Fibrosis Perfusional Variants
Ronot M et al. European J of Rdiol. 2017;93:157-68.
Fatty Infiltration and Sparing• Typical areas of focal fatty sparing are
around the gallbladder & hepatic hilum
– Direct splanchnic venous supply results in a local decrease in lipid rich PV flow
• Focal fatty deposit or sparring in atypical sites can appear nodular
• Distinguishing features of fatty pseudotumor vs. mass containing fat
– No mass effect on vessels and structures
– Geographic configuration as opposed to round/oval shape
– Contrast enhancement similar to normal liver
Kim TK et al. Clinical and Molecular Hepatology 2015;21:326-43.
US Non Contrast CT
Arterial Phase CT T1 Out of Phase
Fatty Infiltration
Kim TK et al. Clinical and Molecular Hepatology 2015;21:326-43.
CT Venous T1 MRI Out of Phase
T1 Venous T1 In Phase T1 Out of Phase
Lesions in Cirrhotic Liver
Metastatic lesions• Rare in cirrhosis
– Alterations in portal flow– 1° neoplasms can spread to a
cirrhotic liver, particularity colorectal adenocarcinoma
Hypervascular Metastatic Dz• Melanoma• Renal Cell
• Choriocarcinoma• Thyroid
• Carcinoid• Pancreas
• Breast
Hepatic Angiosarcoma• Rare tumor; 3rd most common liver
tumor
• Single mass with satellite lesions of infiltrative mass with atypical proliferation of endothelial cells in sinusoids
• High mortality: 2° rupture/ liver failure
– 2 year OS 3%
• Risk factors: vinyl chloride, arsenic, cyclophosphamide, anabolic steroids, OCP
• Therapy: resection + chemotherapy
– OLT contraindicated; poor outcomes
MillianM et al. Int J Surg Case Rep. 2016; 28:165‐68.
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Hepatic Epithelioid Hemangioendothelioma(HEHE)
• Rare tumor: vascular origin
• Non specific sx: RUQ pain, wt loss, BCS, abnormal liver function
• Generally low to intermediate grade– More favorable prognosis than other hepatic malignancies
• Commonly middle age female, median age 41
• Stains: + for 1 of the following endothelial markers:– Factor VIII-related Ag, CD34, CD31– Negative for epithelial markers: cytokeratin and CEA: – MUST distinguish from adenocarcinoma or sarcoma
• Course: prolonged survival to rapidly progressive course
• Treatment:– Resection– OLT: >10 nodules or >4 involved hepatic segments– Anti VEGF therapy
Hepatic Epithelioid Hemangioendothelioma
Peripheral coalescing masses with capsular retraction
Multiple peripheral masses w/ capsular Retraction & more confluent lesions Centrally w/calcification.
Peripheral confluent mass with capsular retraction is the hallmark feature
Histological Classification
Benign Tumors
Epithelial Non‐epithelial Tumor‐like lesions
• Liver cell adenoma• Bile duct adenoma• Bile duct cystadenoma• Biliary papillomatosis
• Hemangioma• Infantile
hemangioendothelioma• Lymphangioma• Angiomyolipoma• Pseudolipoma• Fibroma• Leiomyoma
• Cysts• Fibropolycystic disease• Focal nodular hyperplasia• Nodular regenerative
hyperplasia• Mesenchymal hamartoma• Biliary hamatoma (von• Meyenburg complex)• Inflammatory pseudotumor
Key Points in History
• Constitutional symptoms: anorexia, weight loss
• Prior history of malignancy
• Risk factors for chronic liver disease
• History of foreign travel
• Medications: steroids, OCP
Resection in a Suspected Benign Lesion
• Has there been growth in the lesion?
• Is the lesion atypical or is the diagnosis
in question?
– enhancement pattern
• Is it causing symptoms?
• Is the lesion in a location amendable for resection?
• MRI is preferred imaging modality
– No radiation
– Provides more detail of tissue
• Mutidisciplinary team: hepatologist, hepatobiliary
surgeon, interventional radiologist and pathologist
2016
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Hemangioma
• Most common benign liver lesion; 1-20% population
• Classic appearance: peripheral nodular enhancement with gradual central fill-in
• Bright on T2-weighted images is helpful for confident diagnosis of hemangiomas.
• Can mimic HCC; especially when small and lack centripetal enhancement “filling” in
– Larger lesions may show an avascular zone
– MUST distinguish from malignancy
• Predominant prevalence in woman• Female to male 3:1
• Size generally remains stable• Hormonal influence has been documented to increase size• Single or multiple: most solitary• Size varies from millimeters to 20 cm: most < 5 cm
– > 10 cm giant hemangioma
Hemangioma
Kim TK et al. Clinical and Molecular Hepatology 2015;21:326-43.
Sclerosing Hemangioma: fibrous replacement
T1 Arterial Portal
Hepatobiliary T2
T1 Early Arterial
Late Arterial T2
Typical Hemangioma
Management
• Biopsy not contraindicated if can not make Dx with imaging
– Must have normal parenchyma between the capsule and margin of hemangioma
– Biopsy 96% accurate
• Often asymptomatic; may increase in size over time
• Follow up is not required for typical hemangioma
• NO correlation with size and complication
• Pregnancy & OCP NOT contraindicated with stable, asymptomatic hemangioma
• Symptomatic or giant hemangioma uncommon; refer to multidisciplinary team
Hemangioma vs. ICCA
• Not seen with similar frequency in cirrhosis
– often shrink & become sclerosed in cirrhosis– generally not seen in advanced cirrhosis
– therefore follow up on lesions read as hemangioma
• Atypical hemangioma may represent an intrahepatic cholangiocarcinoma
Clinical Manifestations: Hemangioma• Cardiac failure
• Hypothyroidism – 2° to high levels of enzyme activity
• Kasabach Meritt syndrome: consumptive coagulopathy, more common in > 5 cm– Breaches in EC integrity exposure of sub-endothelial collegen &
tissue factors• platelet aggregation (low platelets) and activation of coagulation
cascade– Reports of development of KMS w/ pregnancy in > 5 cm lesions
• Steroid resistant polymylagia rheumatica
• Hemobilia
• Rupture: large, peripherally located
• Innumerable hemaniomas– Associated with Osler Weber Rendu
Rare manifestations
Focal Nodular Hyperplasia (FNH)• 2ND most common benign hepatic lesion; in autopsy series prevalence 0.4 – 3%
• Contains bile ducts and Kuffer cells; distinguishing from adenoma
• Features:– More frequent in right lobe– 90% female– 80 - 95% solitary– Usually < 5 cm, only 3% > 10 cm
• generally stable in size but can see slow growth
• MRI is nearly 100% specific:– CEUS is more accurate than MRI in FNH <3 cm
• Congenital vascular anomaly:
• Associated with Osler Weber Rendu and hemangiomas
• Hallmark is central scar : Feeding artery- “corkscrew artery”– 15% no central scar present; generally in lesions < 3 cm– 20 – 30% multiple: more seen in pts. w/ vascular liver diseases, i.e. Budd-Chiari
syndrome, obliterative portal venopathy and congenital disorders
Livderatlas.org
Central scar
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Imaging Characteristic: FNH
Pre contrast 25s post contrast 40s post contrast
60s post contrast Delayed phase 10 min post contrast
FNH
• No evidence is pre-malignant lesion– Need to differentiate from fibrolamellar cancer
(calcified central scar seen in 55%)
• Management: conservative regardless of size if patient asymptomatic
– poor correlation between FNH & symptoms, so even with symptoms, treatment is rarely indicated.
– Resection rarely indicated: • pedunculated, expanding, exophytic
lesions
• Pregnancy & OCPs not shown to play a role in development or progression
• When to refer:– Symptomatic patients
• hepatic artery embolization or resection– Pedunculated, expanding, exophytic lesions
*
*unless there is underlying vascular liver disease
Hepatic Adenoma (HCA)
• True incidence not clear:
– 10x < common than FNH
– Estimated prevalence 0.007 – 0.012% population
– Increased incidence in estrogen & androgen use
• Most common in females 35-40 years old: 10:1 F:M
– Usually solitary
• Size: mm to 30 cm: increase with OCP/pregnancy
• Complications:
– Hemorrhage: ≥ 5 cm, exophytic lesions higher risk
• risk factors: inflammatory subtype, pregnancy, OCP in last 6 months, increasing size
• Treatment: selective embolization
• Emergent resection: 5-10% mortality vs.. delayed resection < risk, blood loss, complications
– Degeneration to HCC
Plates of hepatocytes 2-3 cells thick, no bile ducts
HCA
• Estrogen: dose dependent
• Obesity, steatosis, & metabolic syndrome, often multiple (incidence RISING)
• Anabolic androgenic steroids
• Imbalance of hormones: Klinefelter’s, PCOS
• Genetic syndromes:
• Familial adenomatous polyposis (associated with β-catenin)
• Glycogen storage disease: seen in 75% of pts. GSD 1a
– Guidelines: annual US age 0-10, biannual > 10
– Adenoma size/# decreases with optimal metabolic control of GSD
• Maturity onset DM
• Abnormalities of hepatic vasculature & intra hepatic shunt
Subtype Classification of Adenomas
EASL J of Hepatol 2016
Almost exclusively in females
Expression of serum amyloid A &CRP
MRI can identify HNF‐1 and inflammatory subtype with > 90% specificity
EASL Guidelines: Adenoma
Klompenhouwer AJ et al. BJS 2017;104:1695‐03.
Non surgical candidates: Embolization or ablation depending on size
Bx proven β-catenin(irrespective of size)
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EASL Guidelines: Adenoma
Non surgical candidates: Embolization or ablation depending on size
EASL J Hep 2016
HCA:Resection after 6 Months?
• Retrospective study: 194 pts. (194 female) with HCA > 5 cm
Surveillance N= 86
Treatment N = 108
‐Higher BMI (P=0.029)-Smaller baseline HCA (P<0.001)-Centrally located (P<0.001)-Multiple lesions (P=0.001)
‐87% Resection-8.3% TAE-4.6% RFA
- Time-to-event analysis:- -HCA measured at 4 time points: Time of DX, 6 mo., 12 mo., last available scan- n=118 n=108 n=79 n=68
Klompenhouwer AJ et al. BJS 2017;104:1695‐03.
Regression with Time
Regression to ≤ 5 cm, by baseline diameter Regression to ≤ 5 cm, by HCA subtype
58.5% showed regression to < 5 cm after a median of 104 wks.
• 6-month cut-off for assessment of regression of HCA > 5 cm is too early• In females with typical, non-β-catenin HCA could be prolonged to 12 mo. Irrespective of baseline size.
Pregnancy with HCA
• Not discouraged in lesions < 5 cm
• In pregnancy follow with US q 6-12 wks.
– In lesions < 5 cm, not exophytic or growing, no data to support C- section over vaginal delivery
– For growing lesions embolization can be considered
– Prior to 24 wks., surgery may be preferred, especially if peripheral lesion to avoid radiation & IV contrast
Hepatobiliary Agents in MRI
• 2 different hepatobiliary agents:
– gadobenate dimeglumine (Gd-BOPTA)
– gadoxetic acid (Gd-EOB)
• Benefits:
– Can help distinguish FNH vs. Adenoma
– May be used to help suggest diagnosis of small HCC w/o washout
– Helpful detecting metastatic disease
• Concerns:
– Approved at lower dose, so may have less robust arterial phase
– Reported to induce transient hypoxemia
– Need long enough delayed phase to capture biliary excretion
Korean J Radiol. 2011 Jul-Aug; 12(4): 403–415.
Facilitates uptake of hepatobiliary agent
FNH & Adenoma
T2 ADC T1
Arterial Phase Venous Phase Hepatobilary Phase
Albiin N. et al Current Medical Imaging Review 2012;8:107-16.
FNHadenoma
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Simple Hepatic Cyst
• No communication with biliary tree
• 1% of autopsy
• More common – right lobe– in female; large cysts almost exclusively in female
> 50
• Generally no septations– Hemorrhage can cause appearance of septa
• No treatment for asymptomatic cysts– Laproscopic unroofing symptomatic cysts
• Monitor large cysts > 4 cm for growth for stability
• Symptoms or increase in size raises concern for cystadenoma/cystadenocarcinoma
Regev et al. J Am Coll Surg 2001; 193:36
Cystadenoma/Cystadenocarcinoma
• Cystadenoma– More common in females– Present with abdominal
fullness/anorexia– Malignant transformation in
15%– Treatment: enuclueation
• Cystadenmacarcinoma– Generally in elderly– Treatment : formal resection– Better prognosis than CCA
Regev et al. J Am Coll Surg 2001; 193:36.Normal CEA < 3 ng/ml Normal CA19-9 < 33 U/LKoffron A et al Surgery 2004; 136(4):926-36.
Conclusion• The presence of cirrhosis or chronic liver disease is important when
a liver lesion is identified
– increased risk of HCC
• Surveillance for HCC has improved outcomes due to identification of early HCC and curative options
– Liver biopsy is not needed to make a diagnosis of HCC
• Distinguishing HCC from other malignant lesions is crucial
• Most benign liver lesions can be managed conservatively
• Key radiographic features can help distinguish the various benign lesions