1. "Cirrosi epatica e tumori del fegato:
dalla resezione al trapianto"
Alessandro Anselmo MD, Ph.D, FEBST
UOC Chirurgia dei Trapianti
Fondazione Policlinico Tor Vergata

2. • Introduction
• Epidemiology
• Pathophysiology
• Clinical features
• Management
• Prevention

3. Introduction
• Commonest primary malignant tumor of the liver
• 6th
most common cancer in the world
• Third leading cause of cancer related death
• More than 600,000 people die from HCC each year

4. Epidemiology
• Men are more susceptible than women
(male-to-female ratio 3.7 : 1.0)
• Incidence increases with advancing age in all populations
• Cirrhosis is a primary risk factor
• Hepatitis and excessive alcohol are leading causes

5. • Hepatitis B virus - most frequent underlying cause world
wide
• 85% of HCC cases- Eastern and Southeastern Asian and
Sub Saharan Africa (endemic HBV infection)

6. Global Incidence

7. Journal of Hepatology 2012 vol. 56 j 908–943

8. Age-Specific Incidence
Liver cancer program ,American Liver Foundation, Dec,2008

9. Liver cancer program ,American Liver Foundation,
Dec,2008

10. Risk factors
• Chronic hepatitis B or C virus infection.
• Cirrhosis (any etiology)
• Nonalcoholic steatohepatitis.
• Diabetes (metabolic syndrome - likely risk process)
• Europe, North America, and Japan- established cirrhosis

11. Surveillence (EASL,2012)

12. Origin of HCC
• Cirrhotic liver(All causes)
• Noncirrhotic liver
Hepatitis B
Fibrolamellar variant
Metabolic diseases (eg, glycogenosis,
porphyria)
Hepatitis C

13. Incidence related to etiology of cirrhosis
High incidence (>15%)
HBV related
HCV related
Alcoholic
Hemochromatosis
Intermediate incidence (5-15%)
NAFLD
Low incidence (<5%)
Primary biliary cirrhosis
Wilsons disease
Autoimmune hepatitis

14. Pathogenesis
A stepwise process
• Sequential genetic mutations
• Oncogene activation
• Tumor suppressor gene inactivation

15. Key mechanisms in development of HCC Liver cirrhosis
following tissue damage
- Mutations occurring in 1 or more oncogenic or tumor
suppressor genes
-Abnormalities in cellular signaling pathways
Raf/MEK/ERK –PI3K/AKT/mTOR/β-catenin –
Angiogenic signaling

20. Clinical features

21. Clinical features
Small tumour:
• Often asymptomatic
• No physical signs
• Signs related to the chronic liver disease and/or
underlying cirrhosis
Advanced disease:
• Palpable mass in the upper abdomen,
• Hard, irregular liver surface
• Tenderness in the upper right abdominal quadrant
• Splenomegaly, ascites
• Hepatic arterial bruit (heard over the tumor)
WGO practice

22. Suspicion of HCC in patients with previously compensated
cirrhosis:
• Rapid deterioration of liver function
• New-onset (or refractory) ascites
• Acute intra-abdominal bleeding
• Increased jaundice
• Weight loss and fever
• New-onset encephalopathy
• Variceal bleeding

23. Laboratory findings
• Usually nonspecific
• Signs of cirrhosis:
Thrombocytopenia — Hypoalbuminemia —
Hyperbilirubinemia — Coagulopathy
• Electrolyte disturbances
• Liver enzymes- abnormal( but nonspecific)
• Elevated alpha fetoprotein (AFP; requires definitions of
levels and appropriate setting)
• Elevated alkaline phosphatase (ALP)

24. Diagnosis

25. EASL practice guidelines,2012

26. Tumor markers
Marker Sensitivit
y(%)
Specificit
y(%)
Cut off Remarks
AFP Widely
available
a)High
incidence
regions
80-90 90 >10ng/ml
b)Low
incidence
regions
25-65 79-95 16-
200ng/ml
DCP 28-89 87-95 10-
125mAU/
ml
AFP-L3 71 63 >10% Supports
AFP if 10-
200

27. Novel markers
• Glypican 3,
• Golgi protein 73,
• Hepatocyte growth factor,
• Insulin growth factor 1,
• Transforming growth factor-β1
• Clear cutoff values and comparisons with other markers
have not been established

28. Imaging
Ultrasonography
• Detects most hepatocellular carcinomas
• May not distinguish from other solid lesions
• Low sensitivity(48%) & high specificity(97%)

29. Imaging
CT-scan
• Multiphase( dynamic) helical computed
tomography(CT) - imaging technique of choice
• Diagnostic pattern :
- enhancement in the arterial phase
- loss of central nodule enhancement
(washout) in portal venous phase
- capsular enhancement in the portal
venous and delayed phases

31. CT-scan
• Sensitivity and specificity by CT
67.5% and 92.5%
• Lesion is larger than 2 cm in diameter- 100% specificity
• Lesions of 1 to 2 cm - a second type of dynamic imaging
(magnetic resonance imaging [MRI] or contrast
ultrasonography)

32. MRI
• Findings on multiphase contrast enhancement are similar
to those of CT
• Signal intensity on T1-weighted images is low
• Sensitivity and specificity - 80.6% and 84.8%

33. MRI

34. Morpholgy (Robbins Pathologic basis of disease)

35. Treatment (WGO practice guidelines,2009)

36. Treatment recommendations(EASL,2012)

38. “Una ferita al fegato è
fuori dalle nostre cure,
anzi, per evitare che la
gente ci possa ritenere
responsabili della morte
dei parenti, è bene
declinare ogni invito a
intervenire
chirurgicamente.”
Ruggero di Frugardo, chirurgo
salernitano XIII sec.

39. Anatomy, Diagnosis and
preoperatory Planning

40. QuickTime™ e un
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sono necessari per visualizzare quest'immagine.

41. Clampaggi vascolariClampaggi vascolari
a) manovra dia) manovra di
PringlePringle
b) clampaggiob) clampaggio
selettivoselettivo
c) clampaggioc) clampaggio
soprailaresoprailare
d) clampaggiod) clampaggio
intraepaticointraepatico
e) esclusionee) esclusione
vascolarevascolare
totaletotale

42. DIGITOCLASIADIGITOCLASIA

43. KELLYCLASIAKELLYCLASIA

44. COAGULAZIONECOAGULAZIONE
MONOPOLAREMONOPOLARE

45.  GENERATORE
 MANIPOLO CON SET
DI ASSEMBLAGGIO
 ASPIRATORE
CUSA: CAVITATIONAL ULTRASONIC
SURGICAL ASPIRATION

46. COAGULATORE AD ARGON
Rappresenta uno dei
principali ausili nella
chirurgia del fegato per
minimizzare le perdite
ematiche e biliari post
operatorie

47. Radiofrequenza della trancia di sezione
SCOPO ONCOLOGICO
SCOPO EMOSTATICO (pre e post resezione)

48. EMOSTATICI

49. Resezioni x HCC: Quando?Resezioni x HCC: Quando?
In assenza di cirrosi sono suscettibili di terapia
resettiva con intento radicale:
HCC in stadio I
HCC in stadio II
HCC in stadio IIIa (N0)
In assenza di cirrosi sono suscettibili di terapia
resettiva con intento non radicale:
HCC in stadio IIIb (N1)
Non sono resecabili:
HCC in stadio IV

50. Resezioni x HCC: Quando?Resezioni x HCC: Quando?
In presenza di cirrosi oltre allo stadio della neoplasia deve essere
considerato la gravità della epatopatia secondo la classificazione
di Child-Pough
Child A
Child B
Child C
1 2 3
Encephalopathy - Minimal Marked
Ascites - Slight Moderate
Bilirubin <35 35-50 >50
Albumin >35 28-35 <28
INR <1.4 1.4-2.0 >2.0• A – 5-6 points
B – 7-9 points
C – 10-15 points

51. Resezione e TrapiantoResezione e Trapianto
In presenza di cirrosi sono suscettibili di terapia
resettiva
Child A
Child B
In presenza di cirrosi sono suscettibili di
trapianto di fegato
HCC unico ∅ < 5 cm Child C
HCC mutiplo monolobare ∅ max < 5 cm
Child C

52. Sopravvivenza post-resezioneSopravvivenza post-resezione
In assenza di cirrosi il follow-up dopo resezione con
intento curativo
Surv. a 1 anno 71% libero da malattia
Surv. a 3 aa. 50% “
Surv. a 5 aa. 43% “
Surv. a 10 aa. 19% “
In presenza di cirrosi il follow-up dopo resezione con
intento curativo
Surv. a 3 aa. 29% libero da malattia
Surv. a 5 aa. 20% “

53. Sopravvivenza post-trapiantoSopravvivenza post-trapianto
Il follow-up dopo OLTx per HCC surv
attuariale a 5 aa:
Stadio I 75%
Stadio II 68%
Stadio III 52,1%
Stadio IV 11%

54. Resezione Epatica:Resezione Epatica:
TerminologiaTerminologia
- Resezione atipica
- Resezione limitata: 1-3 segmenti
(mono- bi- tri- segmentectomia)
- Resezione maggiore: >3 segmenti
(emiepatectomia dx/sx ± allargata)
- Resezione estrema: >5 segmenti
o ricostruzione vascolare
- Epatectomia totale (→ Trapianto
epatico)

55. Epatectomia
destra

56. Epatectomia
destra

57. Epatectomia
sinistra

58. Epatectomia
sinistra

59. Epatectomia
sinistra

60. Epatectomia
sinistra

61. Lobectomia
sinistra

62. Lobectomia
sinistra

63. Lobectomia
sinistra

64. Segmentectomie

65. 2D “conventional” Laparoscopy
Advantages
• Less surgical trauma
• Less postop. pain
• Shorter postop. ileus and prompt return to oral intake
• Shorter hospital stay
• Faster return to normal activities and work

66. “Hand assisted” Laparoscopy
In hand-assisted laparoscopic surgery (HALS), the
surgeon inserts a hand into the abdomen while
pneumoperitoneum is maintained and uses the hand to
assist the laparoscopic instruments directly.

67. QuickTime™ e un
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70. Laparoscopy
• 3D HD technology restores the surgeon’s natural 3-D vision with
depth perception making the endoscopic surgical field-of-view appear
open.
• This results in optimized hand eye coordination, helping to increase
surgical speed and accuracy, offering clinical and economic benefits to
hospitals and patients globally.
• This is obtained with the use of helmets or polarized lenses glasses

71. Laparoscopy

72. Laparoscopy

73. Laparoscopy

74. Laparoscopy

75. Hand Assisted Laparoscopy

76. Hand Assisted Laparoscopy
Left Nephrectomy for big Epithelioid Angiomyolipoma

77. Hand Assisted Laparoscopy
Left Bisegmentectomy for big Hemangioma of the liver

78. Hand Assisted Laparoscopy
Left Bisegmentectomy for big Hemangioma of the liver

79. Hand Assisted Laparoscopy
Left Bisegmentectomy for big Hemangioma of the liver

80. Hand Assisted Laparoscopy
Left Bisegmentectomy for big Hemangioma of the liver

81. Hand Assisted Laparoscopy
Left Bisegmentectomy for big Hemangioma of the liver

82. Hand Assisted Laparoscopy
Left Bisegmentectomy for big Hemangioma of the liver

83. • Better image quality
• Depth of field
• Tactile feedback • Better ergonomy
• Better precision
• Reduction of postop. complications
• Less stress for the surgeon
• Costs reduction
• Faster postop. recovery
QuickTime™ e un
decompressore H.264
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Laparoscopy
Advantages

85. Robotic Surgery

87. Trapianto di FegatoTrapianto di Fegato

88. Thank you for your attention!