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Management of hepatocellular carcinoma: a case report

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Management of hepatocellular carcinoma: a case report

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    1. Management of hepatocellular carcinoma: a case report Giovanni Brandi

    2. The patient Male, 61 year-old Smoker Alcohol abuse

    3. The patient

    8. 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”.

    10. Treatment options: Barcellona criteria

    11. Liver trasplant: indications 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 ilum’s nodes involvement

    12. Predictors of Long-Term Survival After Liver Transplantation for Hepatocellular Carcinoma.

    13. Predictors of Long-Term Survival After Liver Transplantation for Hepatocellular Carcinoma.

    14. Beyond Milano’s criteria ? From june 2006 to april 2007, 1556 patients transplanted, 1112 exceeding Milano’s 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

    15. The patient A first nodule of 2 cm A second nodule of 1 cm No invasion of main hepatic vessels

    16. Liver Transplant

    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 Daclizumab (Zenapax®) + Tacrolimus Norvasc Lansox Tiklid Bactrim forte Deursil Zyloric Eskim Torvast Aranesp

    19. Adverse event within the immunosoppression/tacrolimus 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

    21. Nephrologic evaluation Ecodoppler: no thrombosis or stenosis in the main renal vessels Renal biopsy

    22. Abdomen ultrasound scan

    23. CT: December 2006

    24. Colonoscopy was performed in order to exclude a large intestine primitive cancer

    25. Survival for recurrence HCC after OLT

    26. Survival for recurrence HCC after OLT

    27. Survival for recurrence HCC after OLT

    29. Treatment options: Barcellona criteria

    30. 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 >3000/1300 platelets> 75000 ; Hb> 10 Bilir up to 3.0; Pt >50% 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

    34. November 2007: we try to restart with HAI-therapy but..

    36. A phase II trial of metronomic capecitabine in HCC Diagnosis of HCC by histology or Barcellona’s criteria Child-pugh cirrhosis A (or B) Unfit for surgery or local treatment Life expectancy > 3 months Bilirubin serum level < 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 (500mg+500mg) without interruption In march 2009 he completed the XIVth cicle of therapy… This is the CT of revaluation…

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