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CASOCLINICO:Manejodelpacientecon
Hepatocarcinoma enestadioprecoz
Dra.ChristiePerelló M.GastroenterologíayHepatología
HospitalUniversitarioPuertadeHierro
INTRODUCCION
• ElCarcinomaHepatocelular(CHC),tumorhepático
primariomasfrecuente.
• Esel6tocáncermasfrecuenteanivelmundial.
• 2dacausademuerteasociadaacáncer.
• AumentodelaincidenciaenEEUUyEuropa
• Principalcausademuerteenlospacientescirróticos.
Relacióntamaño/CHC/Histología
0
10
20
30
40
50
60
70
80
90
100
<3.0 3.1-5.0 5.1-6.5 >6.5
Diámetro tumoral (cms)
%
Pobre Moderado Bienp<0.005
Pawlik TM, et al. Liver Transplant 2005; 11: 1086-92
Relacióntamaño/invasiónvascular
p<0.005
0
10
20
30
40
50
60
70
80
90
100
<3.0 3.1-5.0 5.1-6.5 >6.5
Diámetro tumoral (cms)
%
Invasión microvascular
Invasión vascular macroscópica
Pawlik TM, et al. Liver Transplant 2005; 11: 1086-92
PERFILPACIENTE
Característicasdeltumor
(tamaño,extrah.)
Funciónhepática(Child-Pugh,
MELD)
HipertensiónPortal(GPVH)
Heterogeneidaddelasituaciónclínica
Morfologíatumoral
Child-Pugh/MELD
score
Recuentoplaquetario
Varicesesofágicas
Gradientedepresiónvenosahepática
Nivelesdealfa-fetoproteína
Característicashistopatológicas
Localizacióndeltumor
HeterogeneidadclinicaCaso Edad Diámetro PST AFP Child-
PughMELD Bilirrubina Plaquetas Varices Local.
1 56 18mm 0 4.6 A-5 7 0.9 169000 No II
2 74 17mm 0 10.3 A-5 6 1.0 152000 No III
3 77 17mm 0 3.1 A-6 7 0.8 171000 No IV
4 76 19 mm 0 9.4 A-6 8 1.1 67000 Sí IV
5 51 15mm 0 556.2 A-6 10 1.9 187000 No II
6 49 15mm 1 89.1 B-8 12 2.3 51000 Sí VIII
7 72 12 mm 2 466.3 B-9 10 2.4 44000 Sí IV
Eltratamientoantitumoralideal…
• Elevadaeficaciaantitumoral
• Adecuadoperfildeseguridad
• Mínimainvasividad
• Preservelafuncióndelórganoenfermo
• Posibilidaddeaplicacionesrepetidas
• Perfilfármaco-económicofavorable
Sistemaestadiaje BCLC
Bruix J, et al. Gastroenterology 2016; 379: 1245-55
nodule and among separate nodules.98,99 This poses a majorchallenge to the use of molecular analyses of biopsy speci-mens to determine prognosis or select treatment (see Pinyolet al100 and Borel et al101 for reviews on this subject).
TreatmentThe end point of treatment is to increase survival.
Treatments should not be offered because they are techni-cally possible.102 Treatment indications have been refined,and if patients are not candidates for first-line therapy asper stage, they can be given the treatment for a moreadvanced-stage tumor (treatment stage migration; seeFigure 3).82
BCLC Stage 0Surgery is no longer the only first-line treatment.
Resection, transplantation, and ablation provide excellentresults for single lesions !2 cm (T1 stage) in patients withpreserved liver function.82,102–104 Rates of 5-year survivalrange from 60% to 80%.105,106
Although there has been no robust trial to compare theefficacy of surgery versus ablation,107 case-control andmodeling studies have shown ablation to be noninferior andmore cost-effective for patients with very early-stageHCCs.108,109 There are no data to guide decision makingfor small tumors when patients may be candidates for alloptions. Some have reserved liver transplantation for pa-tients with recurrence of cancer after treatment.110 Others
Figure 2. Staging and treatment according to the BCLC system. The first step in evaluation of patients combines prognosis(upper section) with selection of treatment (lower section). Prognoses are made based on clinical and tumor parameters. As inall recommendations, the treatment should be selected based on a detailed evaluation of characteristics such as the patient’sage and comorbidities. As mentioned in the text, the Child–Pugh classification is not sensitive enough to accurately identifypatients with advanced liver failure who would deserve consideration for liver transplantation. Some patients corresponding toChild–Pugh class B, and even Child–Pugh class A, could have poor outcomes because of events such as spontaneousbacterial peritonitis, recurrent variceal bleeding, refractory ascites, hepatorenal syndrome, recurrent encephalopathy, or severemalnutrition, which are not registered in the Child–Pugh classification. Patients with end-stage cirrhosis due to heavilyimpaired liver function (Child–Pugh class C or earlier stages with predictors of poor outcome, or high Model for End-StageLiver Disease [MELD] scores) should be considered for liver transplantation. In these patients, HCC may become a contra-indication if it exceeds the enlistment criteria. Modified with permission from Forner et al81 and Reig et al.82
April 2016 Diagnosis, Staging, and Treatment of HCC 839
REVIEW
SAN
DPE
RSPE
CTIVES
Casoclínico
• Varónde71años.Año2011• Sinantecedentespersonalesdeinterés
• InfeccióncrónicaVHC(2008),genotipo1b,Fibroscan de21Kpa (F4)no
respondedoraPEG+RBV,condatosdeHTP(gastroscopia:varices
esofágicaspequeñas),sinepisodiospreviosdedescompensaciónclínica.
• Child-Pugh A5 (Bil 0.3,alb 4.6,INR1.0)MELD7
Casoclínico
• Enprogramadevigilancia:ECO(Mayo2011):Detectaunnódulode2cmenelsegmentoIVb.CEUS:ComportamientodinámicodeCHC.
• AFP:3.1ng/ml
Mayo2011
- “Wash in”- “Wash out”
Casoclínico
Casoclínico
• Cuáltratamientoseríaelmasindicado?
– Ablativo
– Quirúrgico
– Trasplantehepático
EstadioBCLC
Bruix J, et al. Gastroenterology 2016; 379: 1245-55
nodule and among separate nodules.98,99 This poses a majorchallenge to the use of molecular analyses of biopsy speci-mens to determine prognosis or select treatment (see Pinyolet al100 and Borel et al101 for reviews on this subject).
TreatmentThe end point of treatment is to increase survival.
Treatments should not be offered because they are techni-cally possible.102 Treatment indications have been refined,and if patients are not candidates for first-line therapy asper stage, they can be given the treatment for a moreadvanced-stage tumor (treatment stage migration; seeFigure 3).82
BCLC Stage 0Surgery is no longer the only first-line treatment.
Resection, transplantation, and ablation provide excellentresults for single lesions !2 cm (T1 stage) in patients withpreserved liver function.82,102–104 Rates of 5-year survivalrange from 60% to 80%.105,106
Although there has been no robust trial to compare theefficacy of surgery versus ablation,107 case-control andmodeling studies have shown ablation to be noninferior andmore cost-effective for patients with very early-stageHCCs.108,109 There are no data to guide decision makingfor small tumors when patients may be candidates for alloptions. Some have reserved liver transplantation for pa-tients with recurrence of cancer after treatment.110 Others
Figure 2. Staging and treatment according to the BCLC system. The first step in evaluation of patients combines prognosis(upper section) with selection of treatment (lower section). Prognoses are made based on clinical and tumor parameters. As inall recommendations, the treatment should be selected based on a detailed evaluation of characteristics such as the patient’sage and comorbidities. As mentioned in the text, the Child–Pugh classification is not sensitive enough to accurately identifypatients with advanced liver failure who would deserve consideration for liver transplantation. Some patients corresponding toChild–Pugh class B, and even Child–Pugh class A, could have poor outcomes because of events such as spontaneousbacterial peritonitis, recurrent variceal bleeding, refractory ascites, hepatorenal syndrome, recurrent encephalopathy, or severemalnutrition, which are not registered in the Child–Pugh classification. Patients with end-stage cirrhosis due to heavilyimpaired liver function (Child–Pugh class C or earlier stages with predictors of poor outcome, or high Model for End-StageLiver Disease [MELD] scores) should be considered for liver transplantation. In these patients, HCC may become a contra-indication if it exceeds the enlistment criteria. Modified with permission from Forner et al81 and Reig et al.82
April 2016 Diagnosis, Staging, and Treatment of HCC 839
REVIEW
SAN
DPE
RSPE
CTIVES
Ablacióntumoral
Imagen modificada, cortesía de Tyco Healthcare y Radionics, Burlington, Massachussets, EE.UU.
EficaciaRFAdependedeldiámetrotumoral
0
10
20
30
40
50
60
70
80
90
100
<30 mm 31-50 mm 51-70 mm 71-80 mm
Diámetro tumoral
% r
espu
esta
com
plet
a
Livraghi T, et al. Radiology 1999; 210: 655-61; Livraghi T, et al. Radiology 2000; 214: 761-8 ; Rossi S,et al. AJR Am J Roentegenol 1998; 170: 1015-22; Shirato K, et al. J Ultrasound Med 2002; 21: 67-76
Beneficiosupervivencia
Lin SM, et al. Gastroenterology 2004; 127: 1714-23; Lin SM, et al. Gut 2005; 54: 1151-6; Shiina S, etal. Gastroenterology 2005; 129: 122-30; Brunello F, et al. Scand J Gastroenterol 2008 ;43: 727-35
0
10
20
30
40
50
60
70
80
90
100
Lin, 2004 Lin, 2005 Shiina, 2005 Brunello, 2008
Supe
rviv
enci
a (%
)
año 1 años 2 años 3
Perfildeseguridad
Peng ZW, et al. Radiology 2012; 262: 1022-33
0
10
20
30
40
50
60
70
80
90
100
Menores Fiebre Dolor Mayores Ascitis Otras Muerte
Even
tos
adve
rsos
(n)
(n=71)Radiofrecuencia
(n=74)Resección
Laradiofrecuenciaescomparableconlaresección
Peng ZW, et al. Radiology 2012; 262: 1022-33
Radiology: Volume 262: Number 3—March 2012 n radiology.rsna.org 1029
VASCULAR AND INTERVENTIONAL RADIOLOGY: Radiofrequency Ablation versus Hepatic Resection Peng et al
survival (P = .111 and P = .163, respectively).
In the surgical resection group, there were no differences between patients with central HCC or periph-eral HCC in terms of overall and recur-rence-free survival (P = .869, P = .088, respectively).
Mortality and MorbidityOne death was considered to be related to treatment, and this occurred in a pa-tient in the surgical resection group with central HCC (Table 4). This patient died of a rupture of esophagogastric varices 3 days after treatment, resulting in an in-hospital mortality rate of 1.4% (one of 74 patients) for the surgical resec-tion group. The corresponding figure for the RF ablation group was 0% (zero of 71 patients). Major complications occurred significantly more often in the surgical resection group (38 of 74 patients) than in the RF ablation group (14 of 71 patients) (P = .009) (Table 5).There was no evidence of tumor-track seeding after percutaneous RF ablation. Pain and fever were the most commonly seen minor complications after treat-ment. Posttreatment fever of more than
RF ablation and 93.6%, 79.0%, and 68.4% with surgical resection; there were no significant differences be-tween these two groups (P = .217). The corresponding recurrence-free survival rates were 75.4%, 65.4%, and 60.0% with RF ablation and 79.4%, 61.6%, and 54.0% with surgical resec-tion. There were no significant differ-ences between these two groups (P = .775).
For patients with HBV viral loads of more than 103 copies per milliliter, the 1-, 3-, and 5-year overall survival rates were 96.3%, 88.9%, and 65.5% with RF ablation and 87.0%, 68.6%, and 56.2% with surgical resection; there were no significant differences between these two groups (P = .095). The corresponding recurrence-free survival rates were 77.9%, 59.2%, and 54.9% with RF ablation and 72.3%, 54.0%, and 49.0% with surgical resection. There were no significant differences between these two groups (P = .219).
In the RF ablation group, there were no differences between patients with central HCC or peripheral HCC in terms of overall and recurrence-free
92.0%, 71.6%, and 61.5% with surgical resection. The survival curve for the RF ablation group was better than that for the surgical resection group (Fig 3a, P = .020). The corresponding recurrence-free survival rates were 86.5%, 74.0%, and 67.0% with RF ablation and 68.0%, 40.0%, and 40.0% with surgi-cal resection. The survival curve for the RF ablation group was better than that for the surgical resection group (Fig 3b, P = .033).
For patients with peripheral HCC, the 1-, 3-, and 5-year overall survival rates were 97.3%, 83.3%, and 65.1% with RF ablation and 87.8%, 68.4%, and 62.9% with surgical resection; there were no significant differences between these two groups (P = .464). The corresponding recurrence-free survival rates were 68.7%, 59.2%, and 54.9% with RF ablation and 82.9%, 66.6%, and 52.9% with surgical resec-tion. There were no significant differ-ences between these two groups (P = .351).
For patients with HBV viral loads of 103 copies per milliliter or less, the 1-, 3-, and 5-year overall survival rates were 98.7%, 86.9%, and 72.2% with
Figure 2
Figure 2: (a) Overall and (b) recurrence-free survival for percutaneous RF ablation (PRFA) and surgical resection (SR) groups.
p=0.048 p=0.548
Radiofrecuencia enBCLC-0:Pros
• Altatasadeaplicabilidad
• Elevadaeficaciaantitumoral
• Adecuadoperfildeseguridadypocoinvasiva
• Noimplicapérdidademasahepáticafuncionante
• Posibilidaddeaplicaciónrepetida
• Relacióncoste-eficaciafavorable
RadiofrecuenciaenBCLC-0:Contra
• Respuesta terapéutica menos predecible.
• Mayor tasa de recurrencia, a expensas derecurrencia local.
• Localizaciones de difícil aplicación (subcapsular,estructuras viscerales, vías, biliares, vasossanguíneos).
• No proporciona características histopatológicas deltumor.
Casoclínico#2
• Mujerde61años.Año2016• HTA,Dislipidemia entratamientoconLosartán 50mg,Simvastatina 10mg
• HepatitiscrónicaNASH,Fibroscan de12Kpa (F3),nodescompensaciones
clínicas.
• Analítica:(Bil 0.9,alb 4,INR1.1)ALT100AST85,Plaq 175
• RevisiónanualconEcografía:Demorfologíanormal,ecogenicidad
alterada.Nódulohepáticode2.5cmsegmentoVII
• AFP16ng/mL
• Biopsia:CHCbiendiferenciado
Casoclínico#2
Biopsia:CHCbiendiferenciado
Cateterismodevenassuprahepáticas:
GPVH:5 mmhg
AusenciadeHipertensiónportalsinusoidal
Casoclínico#2
EstadioBCLC
Bruix J, et al. Gastroenterology 2016; 379: 1245-55
nodule and among separate nodules.98,99 This poses a majorchallenge to the use of molecular analyses of biopsy speci-mens to determine prognosis or select treatment (see Pinyolet al100 and Borel et al101 for reviews on this subject).
TreatmentThe end point of treatment is to increase survival.
Treatments should not be offered because they are techni-cally possible.102 Treatment indications have been refined,and if patients are not candidates for first-line therapy asper stage, they can be given the treatment for a moreadvanced-stage tumor (treatment stage migration; seeFigure 3).82
BCLC Stage 0Surgery is no longer the only first-line treatment.
Resection, transplantation, and ablation provide excellentresults for single lesions !2 cm (T1 stage) in patients withpreserved liver function.82,102–104 Rates of 5-year survivalrange from 60% to 80%.105,106
Although there has been no robust trial to compare theefficacy of surgery versus ablation,107 case-control andmodeling studies have shown ablation to be noninferior andmore cost-effective for patients with very early-stageHCCs.108,109 There are no data to guide decision makingfor small tumors when patients may be candidates for alloptions. Some have reserved liver transplantation for pa-tients with recurrence of cancer after treatment.110 Others
Figure 2. Staging and treatment according to the BCLC system. The first step in evaluation of patients combines prognosis(upper section) with selection of treatment (lower section). Prognoses are made based on clinical and tumor parameters. As inall recommendations, the treatment should be selected based on a detailed evaluation of characteristics such as the patient’sage and comorbidities. As mentioned in the text, the Child–Pugh classification is not sensitive enough to accurately identifypatients with advanced liver failure who would deserve consideration for liver transplantation. Some patients corresponding toChild–Pugh class B, and even Child–Pugh class A, could have poor outcomes because of events such as spontaneousbacterial peritonitis, recurrent variceal bleeding, refractory ascites, hepatorenal syndrome, recurrent encephalopathy, or severemalnutrition, which are not registered in the Child–Pugh classification. Patients with end-stage cirrhosis due to heavilyimpaired liver function (Child–Pugh class C or earlier stages with predictors of poor outcome, or high Model for End-StageLiver Disease [MELD] scores) should be considered for liver transplantation. In these patients, HCC may become a contra-indication if it exceeds the enlistment criteria. Modified with permission from Forner et al81 and Reig et al.82
April 2016 Diagnosis, Staging, and Treatment of HCC 839
REVIEW
SAN
DPE
RSPE
CTIVES
Resecciónhepática
FotosarchivoDr.Turrión
AP:CHCbiendiferenciadosininvasiónmicrovascular niperineural.Márgenesderesecciónlibresdeenfermedadtumoral.
VolumetríaHepática
Hipertensiónportalenlaresección:Elfactorclave
Llovet JM, et al. Hepatology 1999; 30: 1434-40
Ausencia de hipertensión portal o GPVH <10 mmHg
Presencia de hipertensión portal y bilirrubina <1 mg/dL
Presencia de hipertensión portal y bilirrubina >1 mg/dL
Hipertensiónportalenlaresección:Elfactorclave
Berzigotti A, et al. Hepatology 2015; 61: 526-36
the finding of varices is sufficient to confirm the pres-ence of CSPH.27 On the other hand, in patients whohave no varices, platelet count and spleen size are notaccurate enough to rule out CSPH, which is presentin up to 40% of cases.22,28-30 In addition, one studycomparing HVPG to standard noninvasive surrogatecriteria of CSPH (platelet count <100,000/mL andsplenomegaly) in patients undergoing surgery for
HCC showed that surrogate criteria of CSPH werenot able to predict postoperative prognosis, whereasCSPH measured by HVPG confirmed its value. Thesedata, together with the results of the present meta-analysis, strongly suggest that CSPH cannot be confi-dently excluded relying upon the standard noninvasivesurrogate markers, and that the measurement ofHVPG should be used instead, until new more-
Fig. 2. Impact of CSPH on postoperative outcomes of patients with HCC and compensated cirrhosis in all the included studies. (A) Three-yearmortality. (B) Five-year mortality. (C) Clinical decompensation.
HEPATOLOGY, Vol. 61, No. 2, 2015 BERZIGOTTI, REIG, ET AL. 533
the finding of varices is sufficient to confirm the pres-ence of CSPH.27 On the other hand, in patients whohave no varices, platelet count and spleen size are notaccurate enough to rule out CSPH, which is presentin up to 40% of cases.22,28-30 In addition, one studycomparing HVPG to standard noninvasive surrogatecriteria of CSPH (platelet count <100,000/mL andsplenomegaly) in patients undergoing surgery for
HCC showed that surrogate criteria of CSPH werenot able to predict postoperative prognosis, whereasCSPH measured by HVPG confirmed its value. Thesedata, together with the results of the present meta-analysis, strongly suggest that CSPH cannot be confi-dently excluded relying upon the standard noninvasivesurrogate markers, and that the measurement ofHVPG should be used instead, until new more-
Fig. 2. Impact of CSPH on postoperative outcomes of patients with HCC and compensated cirrhosis in all the included studies. (A) Three-yearmortality. (B) Five-year mortality. (C) Clinical decompensation.
HEPATOLOGY, Vol. 61, No. 2, 2015 BERZIGOTTI, REIG, ET AL. 533
the finding of varices is sufficient to confirm the pres-ence of CSPH.27 On the other hand, in patients whohave no varices, platelet count and spleen size are notaccurate enough to rule out CSPH, which is presentin up to 40% of cases.22,28-30 In addition, one studycomparing HVPG to standard noninvasive surrogatecriteria of CSPH (platelet count <100,000/mL andsplenomegaly) in patients undergoing surgery for
HCC showed that surrogate criteria of CSPH werenot able to predict postoperative prognosis, whereasCSPH measured by HVPG confirmed its value. Thesedata, together with the results of the present meta-analysis, strongly suggest that CSPH cannot be confi-dently excluded relying upon the standard noninvasivesurrogate markers, and that the measurement ofHVPG should be used instead, until new more-
Fig. 2. Impact of CSPH on postoperative outcomes of patients with HCC and compensated cirrhosis in all the included studies. (A) Three-yearmortality. (B) Five-year mortality. (C) Clinical decompensation.
HEPATOLOGY, Vol. 61, No. 2, 2015 BERZIGOTTI, REIG, ET AL. 533
3-yearmortality 5-yearmortality
Laresecciónhepáticaescomparableconeltrasplante
Tumor recurrence was observed in 71.6 % (68 of 95) in
the LR group versus 16 % (19 of 119) in the LT group(p \ 0.001). Site of recurrence differed between groups.
One-, 5-, and 10-year cumulative risk of recurrence was 19,
67, and 83 % in the LR group versus 4, 18, and 20 % in theLT group (p \ 0.001) (Fig. 2). Overall mortality was
higher in patients of the LR group 70.5 % (67 of 95) versus
51.3 % (61 of 119), in the LT group (p = 0.004). Differ-ences were also observed in the causes of death.
Survival
No statistical differences were observed in long-term
survival between the LR and LT groups (Fig. 3a). Astratified survival analysis was made between groups. In
the first stratum, 1- and 4-year survival was 85 and 60 % in
the LR group versus 82 and 62 % in the LT group
(p = 0.3) (Fig. 3b). In the second stratum, 10-year survival
was 33 % in the LR group versus 49 % in the LT group
(p = 0.002) (Fig. 3c).
Characteristics and Patient Outcome of LR (Very Earlyand Early HCC) and LT Groups
No differences in preoperative tumor characteristics,
pathologic findings, tumor recurrence, and mortality werefound between the LR groups (very early and early HCC).
It should be noted that according to the ITT principle, a
higher number of patients were included on the waiting listfor salvage transplantation in the very early HCC group
27.3 % (6 of 22) compared to the early HCC group 15.1 %
(11 of 73) (p = 0.2), although this was not statisticallysignificant (Table 2).
Actuarial patient survival at 1, 5, and 10 years was 95,
55, and 50 % in the very early HCC group versus 82, 50,and 29 % in the early HCC group (Fig. 4). One-, 5-, and
10-year disease-free survival was 82, 27, and 27 % in the
very early HCC group versus 81, 35, and 13 % in the earlyHCC group (p = 0.9). After salvage transplantation was
applied (very early HCC group n = 5 and early HCC group
n = 10), no recurrence was observed in the very earlyHCC group versus 40 % in the early HCC group (p = 0.2).
The cumulative risk of recurrence after salvage transplan-
tation at 1, 3, and 10 years was 0, 0, and 0 % in the veryearly HCC group versus 20, 30, and 40 % in the early HCC
group (p = 0.1). Actuarial 1-, 3- and 5-year patient sur-
vival after salvage transplantation was 80, 60, and 60 % inthe very early HCC group versus 80, 70, and 46 % in the
early HCC group (p = 0.8).
Patients in the LT group had larger tumors at pathologicstudy than those in the very early HCC group. Moreover,
the tumor recurrence rate was higher in the very early HCC
group compared to that in the LT group. On the other hand,no differences were observed in 1-, 5-, and 10-year
TABLE 1 continued
Characteristic LR group (n = 95) LT group (n = 119) p
Salvage transplantation 17/49 (34.7 %) –
Gemcitabine ? oxaliplatin 1/49 (2.1 %) 2/5 (40 %)
Radiotherapy – 2/5 (40 %)
Mortality
Overall mortality 67/95 (70.5 %) 61/119 (51.3 %) 0.004
Cause of mortality \0.001
HCC recurrence 48/95 (71.6 %) 16/61 (26.2 %)
HCV recurrence – 15/61 (24.6 %)
LT complications – 27/61 (44.3 %)
Other 19/95 (28.4 %) 3/61 (4.9 %)
LR liver resection, LT liver transplantation, HCV hepatitis C virus, HBV hepatitis B virus, TACE transarterial chemoembolization, RFAradiofrequency ablation, AFP a-fetoprotein, ICU intensive care unit, HCC hepatocellular carcinoma
100
80
60
40
20
LR group (n = 95)LT group (n = 119)
100Years
Cumulative riskof recurrence P < 0.001
864 92 7531
FIG. 2 Cumulative risk of tumor recurrence in the LR and LTgroups
1198 G. Sapisochin et al.
centers in North America, waiting list periods are long, and
LR would probably be more justifiable than at our center,where time on the waiting list was shorter.40 Moreover,
compared to our study analyzing single nodules, both of the
above-mentioned studies included patients with multifocaltumors. Including only patients with single nodules may
make HCC progression on the waiting list less probable,
with a lower dropout rate.Concerning patient survival, many studies reported dif-
ferent 5-year survivals in patients who underwent LR and
those who underwent LT. Those studies included heteroge-neous HCC because patients with uni- and multinodular
tumors were included.16–22 In a previous study conducted at
our department, 5-year survival between groups was similar.41
Although a different cohort of patients was analyzed in
the present study, no differences were observed in 5-year
actuarial survival between patients in the LR and LTgroups. After 5 years of follow-up, both curves separated
dramatically, thereby indicating clear differences in sur-
vival. When actuarial survival was analyzed by strata,patients in the LT group had significantly better long-term
actuarial survival. The poor outcome in the LR group was
expected as a result of the high recurrence rate.However, no differences were observed when a sub-
group of patients with very early HCC was compared to
those of the LT group despite a significantly higher inci-dence of tumor recurrence. Therefore, the poor 10-year
actuarial survival achieved in the LR group was due to
cirrhotic patients with HCC[2 cm. This is one of the mostimportant features of our study.
On the other hand, salvage transplantation in the
setting of tumor recurrence after LR for HCC has beenwidely accepted as a good approach, with excellent post-
transplantation survival rates despite its low appli-
cability.7,27,31–33 In fact, in a recent study conducted in ourdepartment, patients with late recurrence ([12 months)
after LR who underwent salvage transplantation yielded
comparable results to those primarily transplanted.27 Whenthe low applicability of salvage transplantation in patients
with HCC recurrence was analyzed in the present studypopulation (only 22 %), patients with very early HCC were
found to have a higher chance of being transplanted;
however, perhaps owing to the small number of patients,this finding did not reach statistical significance. Moreover,
once the patients had been transplanted, those in the very
early HCC group had a much better outcome, and noneexperienced posttransplantation HCC recurrence; however,
given the small number of patients analyzed, these results
should be considered with caution.In summary, the present study is, to our knowledge, the
first to compare the 10-year outcome of cirrhotic patients
with single HCC B5 cm who underwent LR or LTaccording to ITT analysis. Regarding our results in the
setting of short waiting list time and low dropout, LT
achieved the best long-term outcome in terms of survivaland recurrence. However, when a subgroup of patients with
very early HCC was analyzed, similar 10-year survival was
found compared with the LT group, although the recur-rence rate remained very high.
Thus, we can conclude that for very early HCC in com-
pensated cirrhotic patients, LR is the treatment of choice whentechnically feasible. On the other hand, given the best 10-year
outcome achieved with LT in the early HCC group, we would
recommend transplantation for these patients. It should betaken into account that this study was conducted in the setting
of a short waiting list time, and the applicability of this
approach by other groups should be evaluated by each centeraccording to waiting list and donor potentiality.
ACKNOWLEDGMENT We thank Carlos Margarit, MD, PhD,director of the Liver Transplant Unit until 2005. We thank ChristineO’Hara for valuable English-language revision. We also thank EstherDelgado.
CONFLICT OF INTEREST The authors have no conflicts ofinterest to disclose.
REFERENCES
1. Bruix J, Sherman M; American Association for the Study ofLiver Diseases. Management of hepatocellular carcinoma: anupdate. Hepatology. 2011;53:1020–2.
100
80
60
40
20
100
Years
Actuarial survival
864 92 7531
LT group (n = 122)LR group 2 cm (n = 22)LR group 2 cm (n = 73)
P = 0.90 P = 0.02P = 0.20
FIG. 4 Actuarial patient survival between the B2 cm and[2 cm LRgroups and LT group according to the ITT principle
Liver Resection/Transplantation HCC 1201
p=0.90
Sapisochin G, et al. Ann Surg Oncol 2013; 20: 1194-202
ResecciónenBCLC-0/A:Pros
• Alta eficacia antitumoral.
• Respuesta terapéutica basada en criteriospatológicos.
• Permite conocer las características histopatológicasdel tumor.
• Posibilidad de re-estadiaje intra y postoperatorio.
ResecciónenBCLC-0/A:Contra
• Menor aplicabilidad (HTPCS, función hepatocelular,localización, resecciones amplias).
• Mas invasiva y conlleva a una pérdida de masahepática funcionante.
• Tasa de recurrencia elevada
• Mayores complicaciones y riesgo de disfunciónhepática postoperatoria.
• Mayores costes directos.
Casoclínico#3
• Varónde65años.
• DiagnosticadoenFeb/16:Cirrosisenólica trasun1erepisodiodeHDApor
varicesesofágicasenprofilaxissecundariaconBB+ligadurayascitisenel
contextodelaHDAquecontrolacondiuréticos.Fibroscan 32Kpa (F4).No
otrasdescompensaciones.
• Seismesesantesdeldiagnostico,teniaunaingestadealcoholdiaria(4-5
copasdewhisky).
• Child- Pugh B8:(Bil 2.7,alb 3, INR1.4)MELD15.AFP:22ng/mL
• CHC1,8cmensegmentoVII-VIIIconcriteriosdeHepatocarcinoma
Casoclínico#3
EstadioBCLC
Bruix J, et al. Gastroenterology 2016; 379: 1245-55
nodule and among separate nodules.98,99 This poses a majorchallenge to the use of molecular analyses of biopsy speci-mens to determine prognosis or select treatment (see Pinyolet al100 and Borel et al101 for reviews on this subject).
TreatmentThe end point of treatment is to increase survival.
Treatments should not be offered because they are techni-cally possible.102 Treatment indications have been refined,and if patients are not candidates for first-line therapy asper stage, they can be given the treatment for a moreadvanced-stage tumor (treatment stage migration; seeFigure 3).82
BCLC Stage 0Surgery is no longer the only first-line treatment.
Resection, transplantation, and ablation provide excellentresults for single lesions !2 cm (T1 stage) in patients withpreserved liver function.82,102–104 Rates of 5-year survivalrange from 60% to 80%.105,106
Although there has been no robust trial to compare theefficacy of surgery versus ablation,107 case-control andmodeling studies have shown ablation to be noninferior andmore cost-effective for patients with very early-stageHCCs.108,109 There are no data to guide decision makingfor small tumors when patients may be candidates for alloptions. Some have reserved liver transplantation for pa-tients with recurrence of cancer after treatment.110 Others
Figure 2. Staging and treatment according to the BCLC system. The first step in evaluation of patients combines prognosis(upper section) with selection of treatment (lower section). Prognoses are made based on clinical and tumor parameters. As inall recommendations, the treatment should be selected based on a detailed evaluation of characteristics such as the patient’sage and comorbidities. As mentioned in the text, the Child–Pugh classification is not sensitive enough to accurately identifypatients with advanced liver failure who would deserve consideration for liver transplantation. Some patients corresponding toChild–Pugh class B, and even Child–Pugh class A, could have poor outcomes because of events such as spontaneousbacterial peritonitis, recurrent variceal bleeding, refractory ascites, hepatorenal syndrome, recurrent encephalopathy, or severemalnutrition, which are not registered in the Child–Pugh classification. Patients with end-stage cirrhosis due to heavilyimpaired liver function (Child–Pugh class C or earlier stages with predictors of poor outcome, or high Model for End-StageLiver Disease [MELD] scores) should be considered for liver transplantation. In these patients, HCC may become a contra-indication if it exceeds the enlistment criteria. Modified with permission from Forner et al81 and Reig et al.82
April 2016 Diagnosis, Staging, and Treatment of HCC 839
REVIEW
SAN
DPE
RSPE
CTIVES
Trasplantehepático:CriteriosdeMilán
Mazzaferro V, et al. N Engl Med J 1996; 334: 693-9
Single <5 cm3 nodules, <3 cms
No macrovascular invasion
Factorespronósticosderecidiva
Morfológicos Histológicos Epidemiológicos Bioquímicos
Diámetrotumoral
Númerodenódulos
Invasiónvascularmacroscópica
Pathological tumorstage (pT)
Distribuciónbilobular
Gradodediferenciación
Cápsulatumoral
Invasiónmicrovascular
Nódulossatélites
Sexo
Etiología
InfecciónporVHC
AFP
RegistroEspañoldeTrasplantehepático:
Registro Español de Trasplante Hepático (ONT-SETH). Memoria de Resultados 2015
RETH
MEMORIA DE RESULTADOS 2015
57
RETH
SUPERVIVENCIA DEL PACIENTE SEGÚN LA INDICACIÓN DE TRASPLANTE
RECEPTORES ADULTOS. 1991-2015
Supervivencia 1 mes 3 meses 1 año 3 años 5 años 10 años 15 años 20 años
Colestasis sin carcinoma (948) 94.1% 92% 89.3% 85.8% 84.3% 76.8% 66.4% 58.3% Metabólicas sin carcinoma (414) 95.4% 93% 87.8% 82.5% 77.7% 70.1% 62.5% 50.6% Fallo agudo/subagudo (735) 82.9% 78.9% 76.6% 73.9% 71.8% 66.6% 60% 54.1% Cirrosis sin carcinoma (9962) 95% 91.4% 85.9% 79.3% 74.2% 62.3% 51% 40.2% Hepatocarcinoma (5271) 96.6% 94.2% 87.3% 75.8% 67.8% 53.6% 41.1% 31.5% GLOBAL Wilcoxon Test p< 0.01
Todas comparaciones p< 0.05
RETH
MEMORIA DE RESULTADOS 2015
59
RETH SUPERVIVENCIA DEL PACIENTE SEGÚN LA PATOLOGÍA DE BASE
ADULTOS. TX ELECTIVOS. 1991-2015
Supervivencia 1 mes 3 meses 1 año 3 años 5 años 10 años 15 años 20 años
Cirrosis alcohólica aislada* (4464) 95.9% 92.3% 88.2% 83% 78.8% 65.9% 53.4% 42.8% Hepatocarcinoma (5151) 96.6% 94.2% 87.3% 75.6% 67.6% 53.5% 41% 31.3% Cirrosis Viral aislada* (3317) 94.3% 90.7% 82.8% 74.9% 69% 58.5% 47.9% 37.5% *Sin 2º diagnóstico y AcVHC negativo
GLOBAL Wilcoxon Test p< 0.01
Todas comparaciones p< 0.05 excepto Hepatocarcinoma vs Cirrosis viral aislada
RETH
MEMORIA DE RESULTADOS 2015
59
RETH SUPERVIVENCIA DEL PACIENTE SEGÚN LA PATOLOGÍA DE BASE
ADULTOS. TX ELECTIVOS. 1991-2015
Supervivencia 1 mes 3 meses 1 año 3 años 5 años 10 años 15 años 20 años
Cirrosis alcohólica aislada* (4464) 95.9% 92.3% 88.2% 83% 78.8% 65.9% 53.4% 42.8% Hepatocarcinoma (5151) 96.6% 94.2% 87.3% 75.6% 67.6% 53.5% 41% 31.3% Cirrosis Viral aislada* (3317) 94.3% 90.7% 82.8% 74.9% 69% 58.5% 47.9% 37.5% *Sin 2º diagnóstico y AcVHC negativo
GLOBAL Wilcoxon Test p< 0.01
Todas comparaciones p< 0.05 excepto Hepatocarcinoma vs Cirrosis viral aislada
TrasplanteenBCLC-0/A:Pros
• Alta eficacia antitumoral
• Beneficio significativo en supervivencia con baja tasade recurrencia.
• Respuesta terapéutica basada en criteriospatológicos.
• Permiten evaluar las características histopatológicasdel tumor (confirmación, estadiaje).
TrasplanteenBCLC-0/A:Contra
• Desproporción entre receptores en lista y donantes
• Existe la posibilidad de exclusión por progresión ypeores resultados por intención de tratamiento.
• La ausencia de prioridad en lista hasta progresión
• El impacto de morbimortalidad asociada altrasplante (complicaciones quirúrgicas, infecciones,neoplasias de novo, eventos cardiovasculares,disfunción renal).
• Elevados costes directos.
Trasplantehepático
Resecciónhepática
Ablaciónpercutánea
Supervivencia +++ +++ +++
Eficaciaoncológica +++ +++ ++
Tasaderecurrencia + ++ ++
Eliminacióndeenfermedadpre-
neoplásica
Sí No No
Pérdidademasahepática No Sí No
Aplicabilidad ++ + +++
Costes +++ ++ +
Invasividad +++ +++ +
Evaluaciónderespuesta +++ +++ +
CONCLUSIONES• ElHepatocarcinoma enestadioprecozsueleser
asintomático.
• Esesencialrealizarpruebasdecribadoconecografíacada6mesesenpacientesconcirrosis
• Eldiagnosticoytratamientoprecoztieneunimpactopositivoenlasupervivenciaglobalyenlasupervivencialibrederecurrencia.
• ElCHCprecozsepuedepresentarensituacionesclínicasmuyheterogéneasporloqueesimprescindibleindividualizareltratamiento
UnidadHepatologíaHUPH