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Management of hepatocellular carcinoma: a case report

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Giovanni Brandi Institute of Hematology end Medical Oncology L e A Ser gnoli Bologna University Management of hepatocellular carcinoma: a case report – PowerPoint PPT presentation

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Title: Management of hepatocellular carcinoma: a case report


1
Management of hepatocellular carcinoma a case
report
  • Giovanni Brandi

Institute of Hematology end Medical Oncology L e
A Seràgnoli Bologna University
2
The patient
  • Male, 61 year-old
  • Smoker
  • Alcohol abuse

In 1999 first ascitic failure
Diagnosis of chronic C hepatitis
3
The patient
In 2000 refractory ascitis
Right atrium
Hepatic veins
Transjugular Intrahepatic Portosystemic
Shunt (TIPSS)
TIPSS
Portal Vein
4
March 2002
Abdomen ultrasound scan nodular lesion in the
VI hepatic segment.
CT scan negative
?
5
June 2004
Abdomen ultrasound scan multiple hepatic
nodular formations.
CEUS HCC nodule in the VI hepatic segment.

CT scan negative
?
6
August 2004
MRI HCC nodule in the VII hepatic segment.

December 2004
CT scan HCC nodule in the VIII hepatic segment
7
April 2005
Abdomen ultrasound scan multiple nodular
lesion, the largest in the VI hepatic segment.

May 2005
CT scan Nodular HCC between V and VI hepatic
segment, a second lesion in the II segment and a
third in the VII segment
8
?FP always within the normal range
  • July 2005 chemoembolization of the
  • largest nodule (3,4 cm).
  • CEUS complete response in
  • the lesion treated 2 residual
  • lesions in the remaining
  • parenchyma. Multiple
    rigenerative
  • nodules.

9
15 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
Which is the best treatment for this patient?
Select between
Liver transplant
Surgical resection
Termoablation
Yttrium
10
Treatment options Barcellona criteria
11
Liver trasplant indications
Milanos criteria
  • Solitary nodule with less than 5 cm of diameter
    or
  • Less than 3 nodules with each less than 3 cm of
    diameter and
  • No gross vascular invasion and
  • No ilums nodes involvement

Mazzaferro V. et al. NEJM 1996
12
Predictors of Long-Term Survival After
LiverTransplantation for Hepatocellular
Carcinoma.
Survival by grade
Zavaglia et al. Am. J. G. 2005
13
Predictors of Long-Term Survival After
LiverTransplantation for Hepatocellular
Carcinoma.
Zavaglia et al. Am. J. G. 2005
14
Beyond Milanos criteria ?
Mazzaferro V. et al. Lancet 2009
  • From june 2006 to april 2007, 1556 patients
    transplanted, 1112 exceeding Milanos criteria
  • Median size of largest nodule 40 mm
  • Median numbers of nodule 4
  • 41 of microvascular invasion()
  • 5-years OS 53 vs 73 in patient meet criteria

worst prognostic factor
15
The patient
  • A first nodule of 2 cm
  • A second nodule of 1 cm
  • No invasion of main hepatic vessels

16
Liver Transplant
February 2006
Anastomosis between celiac tripode of the graft
and accessory left hepatic artery of the receiver
17
Pathologist exam of the explanted liver
  • Solitary HCC nodule, almost necrotic (the one
    treated by chemoembolization)
  • Multiple rigenerative nodules
  • Diffuse, microscopic vascular invasion
  • HCC G2-G3 by Edmodson degrees

18
Immunosoppression and other therapies
Immunosoppression protocol
  • Norvasc
  • Lansox
  • Tiklid
  • Bactrim forte
  • Deursil
  • Zyloric
  • Eskim
  • Torvast
  • Aranesp
  • Daclizumab
  • (Zenapax)
  • Tacrolimus

19
Adverse event within the immunosoppression/tacroli
mus
  • Infections
  • Decrease of renal function
  • CNS impairment (headache, trembling,
    depression..)
  • Cytopenia
  • Hirsutism
  • Diabetes mellitus
  • Increase incidence of lymphoma
  • ..

20
Follow-up
  • Progressive increase of creatinine
  • Emerging albuminuria

Dose reduction of Tacrolimus then switch to
Sirolimus
21
Nephrologic evaluation
October 2006
  • Ecodoppler no thrombosis or stenosis in the main
    renal vessels
  • Renal biopsy

Nephropaty with mesangial deposition of IgA
22
  • Abdomen ultrasound scan

Suspect for hepatic lesion
23
CT December 2006
Pet-CT January 2007
Only the largest was seen on FDG-TC-PET.
Multiple microscopic hepatic lesions. One
macroscopic nodule.
24
  • Colonoscopy was performed in order to exclude a
    large intestine primitive cancer

Negative
Hepatic biopsy
Recurrence of HCC
25
Survival for recurrence HCC after OLT
Survival from transplant
P lt 0.0001
Roayaie et al. Liver Trasplantation 2004
26
Survival for recurrence HCC after OLT
Survival from time of recurrence
Time from transplant to recurrence of
hepatocellular carcinoma (P 0.0015)
Roayaie et al. Liver Trasplantation 2004
27
Survival for recurrence HCC after OLT
Survival from time of recurrence
Presence of bone metastases (P 0.002)
Roayaie et al. Liver Trasplantation 2004
28
15 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
Which is the best treatment for this patient,
now?
Select between
Chemotherapy
Surgical resection
Experimental treatment
Termoablation
29
Treatment options Barcellona criteria
July 2008
30
Phase I/II trial of continuous hepatic arterial
infusion (HAI) of Irinotecan in patients with
hepatocellular carcinoma (HCC).
  • Efficacy of irinotecan on HCC cell lines
  • Low efficacy of intravenous irinotecan in HCC (
    Boige V et al 2006)
  • HCC nodules are supplied only by arterial flow
  • Possibility to deliver a higher amount of drug
    into tumoral vasculature
  • Higher conversion of CPT-11 in SN-38 during HAI
    vs IV administration ( Van Riel JHM, 2002)
  • Lower systemic toxicity in HAI vs IV CHT
    administration
  • Irinotecan is a phase specific drug prolonged
    infusion increase fractional cell kill, produces
    lower peak-plasma drug concentration avoiding
    carboxylestease saturation and theoretically
    increasing glucoronation of SN-38 with reduced
    systemic toxicity (Gerrits CJ 1997)

31
Eligibility criteria
  • INCLUSION
  • Pts with HCC on Child-Pugh A/B cirrhosis not
    eligible for curative treatment according to
    Barcelona consensus criteria
  • Absent or incomplete portal vein thrombosis or
    present in only one branch
  • Pts untreated with systemic CHT
  • or submitted to previous TAE, RF
  • with at least 1 measurable active lesion
  • leuko/neutro gt3000/1300
  • plateletsgt 75000 Hbgt 10
  • Bilir up to 3.0 Pt gt50
  • EXCLUSION (main)
  • HCC without cirrhosis
  • Child-Pugh C
  • Complete portal vein thrombosis
  • Metastatic disease
  • History of differents neoplasias..
  • Recent AMI pregnancy.
  • DLT
  • One G4 haematological and/or
  • Two G3 non-haematological toxicities (exepting
    nausea, vomiting, alopecia)
  • Liver function impairment (Child C)

32
  • June 2007 First infusion of CPT-11 (20mg/m²).
  • July 2007 second infusion
  • August 2007 third infusion then
  • Hospitalization for worsening of chronic kidney
    failure

33
Hepatic arteriography
Disease progression
34
  • November 2007 we try to restart with HAI-therapy
    but..

Arteritis (CHT-induced)
Treatment interruption
35
15 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
OKand now?
Select between
Systemic chemotherapy
Antiangiogenic therapy
Experimental treatment
Yttrium
36
A phase II trial of metronomic capecitabine in HCC
Inclusion criteria
Exclusion criteria
  • Diagnosis of HCC by histology or Barcellonas
    criteria
  • Child-pugh cirrhosis A (or B)
  • Unfit for surgery or local treatment
  • Life expectancy gt 3 months
  • Bilirubin serum level lt 3 mg/dl
  • Child-pugh cirrhosis C
  • Chronic heart failure
  • Chronic kidney failure
  • No bone marrow impairment
  • Hypersensitivity at 5-FU

37
  • In december 2007 the patients starts with Xeloda
    1000 mg/daily (500mg500mg) without interruption
  • In march 2009 he completed the XIVth cicle of
    therapy
  • This is the CT of revaluation

38
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39
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