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CENTER OF GENERAL SURGERY AND LIVER TRANSPLANTATION – FUNDENI CLINICAL INSTITUTE – BUCHARESTCENTER OF GENERAL SURGERY AND LIVER TRANSPLANTATION – FUNDENI CLINICAL INSTITUTE – BUCHAREST

IInternational nternational AAssociation of ssociation of SSurgeons and urgeons and GGastroenterologistsastroenterologists

Romanian Society of SurgeryRomanian Society of Surgery RomtransplantRomtransplant

The V-th Symposium andThe V-th Symposium and PPostostgraduate Course ofgraduate Course of IASG IASG

- honoring Th. E. Starzl - - honoring Th. E. Starzl - Bucharest 9-11 April 2003Bucharest 9-11 April 2003

MULTIMODAL TREATMENT MULTIMODAL TREATMENT OF HEPATOCELLULAR OF HEPATOCELLULAR

CARCINOMACARCINOMA

MULTIMODAL TREATMENT MULTIMODAL TREATMENT OF HEPATOCELLULAR OF HEPATOCELLULAR

CARCINOMACARCINOMA

Center of General Surgery and Center of General Surgery and Liver TransplantationLiver Transplantation

Fundeni Clinical InstituteFundeni Clinical InstituteBucharestBucharest

IRINEL POPESCUIRINEL POPESCU


In the Western and Asian experience 70% In the Western and Asian experience 70% of hepatocellular carcinoma (HCC) occurs in of hepatocellular carcinoma (HCC) occurs in patients with cirrhosis, as the most severe patients with cirrhosis, as the most severe complication of this disease (especially complication of this disease (especially macronodular – regenerative)macronodular – regenerative)

There are series in which the proportion is There are series in which the proportion is inversed on behalf of HCC occurring in inversed on behalf of HCC occurring in normal liversnormal livers

The treatment is not standardizedThe treatment is not standardized HCC is one of the most treatment-resistant HCC is one of the most treatment-resistant

tumorstumors For the majority of the patients the chances For the majority of the patients the chances

of cure are still limitedof cure are still limited


AVAILABLE THERAPEUTICAL AVAILABLE THERAPEUTICAL METHODSMETHODS

surgical resectionsurgical resection transplantationtransplantation TAE – transarterial embolizationTAE – transarterial embolization systemic chemotherapysystemic chemotherapy chemoembolizationchemoembolization immunochemotherapyimmunochemotherapy various forms of in situ ablationvarious forms of in situ ablation

PEIT – percutaneous ethanol injection therapyPEIT – percutaneous ethanol injection therapy crcryyoosurgerysurgery radiofrequencyradiofrequency microwavesmicrowaves laserlaser

various methods of radiotherapyvarious methods of radiotherapy


1. SURGICAL RESECTION1. SURGICAL RESECTION 1. SURGICAL RESECTION1. SURGICAL RESECTION the preferred method of treatment in the preferred method of treatment in non-non-

cirrhotic patientscirrhotic patients Surgery for hepatocellular carcinoma has Surgery for hepatocellular carcinoma has

improved dramatically during the last two improved dramatically during the last two decadesdecades11

development of intraoperative ultrasound-development of intraoperative ultrasound-guided operative procedures such as guided operative procedures such as Makuuchi's segmentectomyMakuuchi's segmentectomy

establishment of the precise criteria for establishment of the precise criteria for indications of various hepatectomy proceduresindications of various hepatectomy procedures

use of preoperative portal vein embolizationuse of preoperative portal vein embolization

1 Makuuchi M et al. – Oncology 2002, 62 Suppl 1, 74


RESECTIONRESECTIONIN NON-CIRRHOTIC PATIENTSIN NON-CIRRHOTIC PATIENTS

Anatomical resections are indicatedAnatomical resections are indicated In selected patients with large tumors In selected patients with large tumors ((more thanmore than

5-10 cm5-10 cm diameter diameter)) resection may also be resection may also be performed ab initioperformed ab initio1,21,2 or following or following emboliza embolization tion // ligaturligature of ae of a portal portal venous branch (this allows venous branch (this allows hhyypertrofpertrofy of the y of the contralateral contralateral lobe and lobe and preveprevents nts postoperative liver failure)postoperative liver failure)3,43,4

Yamamoto et al.Yamamoto et al.55: the use of a : the use of a remnant tumor remnant tumor indexindex in palliative reduction surgery for advanced in palliative reduction surgery for advanced hepatocellular carcinomahepatocellular carcinoma

1 Usatoff V et al. – Hepatogastroenterology 2001, 48, 461 Usatoff V et al. – Hepatogastroenterology 2001, 48, 462 Hanazaki K et al. – Hepatogastroenterology 2002, 49, 5182 Hanazaki K et al. – Hepatogastroenterology 2002, 49, 5183 Makuuchi M – Hepatogastroenterology 2002, 49, 363 Makuuchi M – Hepatogastroenterology 2002, 49, 36

4 Popescu I et al. – Chirurgia 2002, 97, 4594 Popescu I et al. – Chirurgia 2002, 97, 4595 Yamamoto K et al. – Arch Surg 1994, 132, 1205 Yamamoto K et al. – Arch Surg 1994, 132, 120


Postoperative mortalityPostoperative mortality

around 2-3% in Western studiesaround 2-3% in Western studies1,21,2

approaching 0% in Asian seriesapproaching 0% in Asian series33

1 1 BismuthBismuth H et al. - H et al. - World J SurgWorld J Surg 19951995, 19, 35, 19, 352 Belghiti J et al. – Hepato-Gastroenterology 2002, 49, 41 2 Belghiti J et al. – Hepato-Gastroenterology 2002, 49, 41 3 Makuuchi M - 3 Makuuchi M - HepatogastroenterologyHepatogastroenterology 2002, 49, 36


DebulkingDebulkingIn selected cases (i.e. non-cirrhotic In selected cases (i.e. non-cirrhotic

patients with large tumors and patients with large tumors and bilateral metastases)bilateral metastases)

1 1 Lau Lau WY – WY – J R Coll Surg Edinb 20022002, 47, 389, 47, 389 2 2 ShimamuraShimamura Y et al. - Y et al. - Hepatogastroenterology 1993 1993, 40, 10, 40, 10

resection of the tumor resection of the tumor („debulking”) („debulking”) and and association of other treatment methods association of other treatment methods

for the remaining for the remaining nodunodulesles1,21,2


Postoperative mortalityPostoperative mortality in in chronic liver disease (CLD) chronic liver disease (CLD)

patientspatients – mortality of 4-7% – mortality of 4-7%

Belghiti J et al. – Hepato-Gastroenterology 2002, 49, 41 Belghiti J et al. – Hepato-Gastroenterology 2002, 49, 41

RESECTION IN CIRRHOTIC RESECTION IN CIRRHOTIC PATIENTSPATIENTS


Preoperative assessment of Preoperative assessment of surgical surgical risriskk

evaluation of evaluation of liver functionliver function volumvolume and quality of the remaining parenchymae and quality of the remaining parenchyma age of the patientage of the patient biologicbiological statusal status

resection is recommended in resection is recommended in Child AChild A cirrhotic cirrhotic patients, but: patients, but: even in these patients the risk of postoperative liver even in these patients the risk of postoperative liver

failure still existsfailure still exists the relatively frequent recurrences don’t seem to justify the relatively frequent recurrences don’t seem to justify

the resectionthe resection


Assessing the risk for resection Assessing the risk for resection in CLD patientsin CLD patients

prediction scores for postoperative prediction scores for postoperative mortality according to Child-Pugh mortality according to Child-Pugh classificationclassification

indocindocyyaninanine-green test at 15 minutes e-green test at 15 minutes (ICG-15’)(ICG-15’)1,21,2

mandatory histological mandatory histological examexamination of ination of the remaining parenchyma before the remaining parenchyma before taking a surgical decisiontaking a surgical decision33

1 Makuuchi M – Hepatogastroenterology 2002, 49, 362 Hemming AW et al. – Am.J.Surg. 1992, 163, 5153 Takenaka K et al. – World J Surg. 1990, 14, 123


Type of resection for HCC in Type of resection for HCC in cirrhotic patientscirrhotic patients

major hepatectomies and wedge major hepatectomies and wedge resections were abandonedresections were abandoned

anatomical segmental resections are anatomical segmental resections are preferred:preferred: conserve liver parenchyma (thus preventing conserve liver parenchyma (thus preventing

postoperative liver failure)postoperative liver failure) similar results as major resectionssimilar results as major resections1,21,2; this ; this

conservative approach was not accompanied conservative approach was not accompanied by an increase in positive resection marginsby an increase in positive resection margins33

1 1 BillingsleyBillingsley KG et al. – J Am Coll Surg KG et al. – J Am Coll Surg 1998 1998, 187, 471, 187, 4712 2 RegimbeauRegimbeau JM et al - Surgery JM et al - Surgery 2002 2002, 131, 311, 131, 3113 3 FanFan ST et al. – Ann Surg ST et al. – Ann Surg 1999 1999, 229, 322, 229, 322


Recurrence of HCC after Recurrence of HCC after surgical resectionsurgical resection

66% at 5 years66% at 5 years11

factors influencing recurrencefactors influencing recurrence22:: tumor sizetumor size multiple tumorsmultiple tumors vascular invasionvascular invasion high preoperative AFP levelshigh preoperative AFP levels histological Edmonson classificationhistological Edmonson classification33

resection marginresection margin44

perioperative blood transfusionperioperative blood transfusion55

delineation: the type of recurrencedelineation: the type of recurrence multicentric metachronous hepatocarcinogenesis (less than 3 multicentric metachronous hepatocarcinogenesis (less than 3

nodules – surgically respectable)nodules – surgically respectable) multinodular recurrences by metastatic dissemination through multinodular recurrences by metastatic dissemination through

portal system, with no possibility of surgical treatment and portal system, with no possibility of surgical treatment and with a dismal prognoiswith a dismal prognois66

correlated

1Sherman M - The Gastroenterologist, 1995, 3, 551Sherman M - The Gastroenterologist, 1995, 3, 552 Fong Y et al. – Ann Surg 1999, 229, 7902 Fong Y et al. – Ann Surg 1999, 229, 7903 Liver Cancer Study Group of Japan – 19943 Liver Cancer Study Group of Japan – 1994

4 Lee CS et al. – Br J Surg 1996, 93, 3304 Lee CS et al. – Br J Surg 1996, 93, 3305 Yamamoto J, Makuuchi M et al. Surgery 1994, 115, 3035 Yamamoto J, Makuuchi M et al. Surgery 1994, 115, 3036 Adachi E et al. - Surgery 2002, 131, S1486 Adachi E et al. - Surgery 2002, 131, S148


Repeat resections for recurrent Repeat resections for recurrent HCCHCC

may be successfully performed in selected casesmay be successfully performed in selected cases1-41-4

more difficult than the primary resection due, first more difficult than the primary resection due, first of all, to the modified vascular anatomyof all, to the modified vascular anatomy

intraoperative US permits localization of intraoperative US permits localization of intrahepatic recurrencesintrahepatic recurrences

alternative in cirrhotic patients: destruction by alternative in cirrhotic patients: destruction by interstitial ablationinterstitial ablation

aggressive treatment of recurrent HCC may aggressive treatment of recurrent HCC may prolong survivalprolong survival

1 Popescu I et al - Chirurgia (Buc ) 1998, 93, 871 Popescu I et al - Chirurgia (Buc ) 1998, 93, 872 Hu R-H et al. - Surgery 1996, 120, 232 Hu R-H et al. - Surgery 1996, 120, 23

3 Poon RT et al. - J Am Coll Surg 2002, 195, 3113 Poon RT et al. - J Am Coll Surg 2002, 195, 3114 4 Lo CM et al. - Br J Surg 1994, 81, 1019Lo CM et al. - Br J Surg 1994, 81, 1019


Five year survival following Five year survival following resection of HCCresection of HCC

steady increase during the last 4 decadessteady increase during the last 4 decades 3% 3% in the in the ’60’60 12%12% in the in the ’70 ’70 4040-50-50% % after the ’80, followingafter the ’80, following increased increased

limited resection for small HCClimited resection for small HCC resection for early detected recurrencesresection for early detected recurrences cytoreductive or sequential resections in tumors prior cytoreductive or sequential resections in tumors prior

considered non-resectableconsidered non-resectable11

limiting resection to patients with Child A cirrhosis (5 limiting resection to patients with Child A cirrhosis (5 year survival in Child B – only 10%)year survival in Child B – only 10%)22

1 Tang ZY et al. - Sem Surg Oncol 1993, 9, 2932 Shirabe K et al. – Cancer 1998, 83, 2312


2. LIVER TRANSPLANTATION2. LIVER TRANSPLANTATION 2. LIVER TRANSPLANTATION2. LIVER TRANSPLANTATION

still under debatestill under debate LTx from cadaver donors is practically LTx from cadaver donors is practically

prohibited by the organ shortageprohibited by the organ shortage solutions: DOMINO LTx / LIVING DONOR LTxsolutions: DOMINO LTx / LIVING DONOR LTx

risk of a high rate of recurrence risk of a high rate of recurrence (immunosuppression)(immunosuppression)


H BismuthH Bismuth11:: liver transplantationliver transplantation offers a disease-free offers a disease-free

survival that is better than after liver survival that is better than after liver resection, and similar to the survival of resection, and similar to the survival of liver transplantation for benign liver liver transplantation for benign liver diseasedisease

patients with contraindications to patients with contraindications to transplantation, patients in whom a long transplantation, patients in whom a long waiting- time before transplantation is waiting- time before transplantation is anticipated, and patients in countries with anticipated, and patients in countries with limited access to transplantation can be limited access to transplantation can be treated with a palliative intent (because of treated with a palliative intent (because of de novo tumors) by de novo tumors) by liver resectionliver resection

1 Bismuth H – Zentralbl Chir 2000, 125, 647


Selection criteriaSelection criteria the selection criteria differ between the selection criteria differ between

various centers but the mostly used are various centers but the mostly used are the Milan Criteriathe Milan Criteria

LTx is indicated in a LTx is indicated in a subgroup of patients subgroup of patients with compensated cirrhosis and HCCwith compensated cirrhosis and HCC small tumors (up to 3.0 cm, or 5 cm if solitary)small tumors (up to 3.0 cm, or 5 cm if solitary) no more than 3 nodulesno more than 3 nodules absence of portal vein tumor thrombusabsence of portal vein tumor thrombus

in some cases with tumors greater than 5 in some cases with tumors greater than 5 cmcm,, transplantation was possible following transplantation was possible following reduction of the tumor size after reduction of the tumor size after chemoembolizachemoembolizationtion1-41-4

1 Schwartz ME et al. – J Am Coll Surg 1995, 180, 5962 Van Thiel DH et al. – J Surg Oncol 1993, 3, 78

3 Olthoff KM et al. – Arch Surg 1990, 125,12614 Moreno Gonzalez E et al. – Am J Surg 1992, 163, 395


in the opinion of some centers with in the opinion of some centers with experienceexperience LTx is indicated also LTx is indicated also in in non-cirrhotic patientsnon-cirrhotic patients non-resectable bilobar tumorsnon-resectable bilobar tumors limited recurrences following resection limited recurrences following resection

(there is a slow progression of this (there is a slow progression of this subtype of HCC)subtype of HCC)

DurandDurand F & Belghiti J - Hepatogastroenterology F & Belghiti J - Hepatogastroenterology 2002 2002, 49, 47, 49, 47


PreTx tumor biopsyPreTx tumor biopsy: strongly indicated : strongly indicated by some authors for the selection of the by some authors for the selection of the patientspatients

high high gradinggradingsize >size > 4 cm 4 cm

predictorpredictors of vascular invasions of vascular invasion – – important important element element affecting the survivalaffecting the survival

Esnaola NF et al. – J Gastrointest Surg 2002, 6, 224


Survival following Tx for Survival following Tx for cirrhotic patients with HCCcirrhotic patients with HCC

at at 3 3 yearsyears it nears survival of non-HCC it nears survival of non-HCC patients transplanted for cirrhosispatients transplanted for cirrhosis (70- (70-80%)80%)11

atat 5 5 years - years - 44%44% iin practicn practice:e: good prognosis especially for good prognosis especially for

those patients with incidentally discovered those patients with incidentally discovered tumors at the time of transplantation (in tumors at the time of transplantation (in which the indication for LTx was which the indication for LTx was determined by the determined by the evoluevolution of cirrhosis, tion of cirrhosis, not by the tumor)not by the tumor)

1 1 DurandDurand F & Belghiti J - F & Belghiti J - Hepatogastroenterology, 2002Hepatogastroenterology, 2002, 49, 47, 49, 47


3. A3. ARTERIAL RTERIAL EEMBOLIZAMBOLIZATIONTION3. A3. ARTERIAL RTERIAL EEMBOLIZAMBOLIZATIONTION

recommended because of the well-recommended because of the well-known arterial hypervascularization known arterial hypervascularization of the HCCof the HCC

its efficiency is still under debate its efficiency is still under debate

Berger DH – J Surg Oncol 1995, 60, 116Berger DH – J Surg Oncol 1995, 60, 116


4. CHEMOTHERAPY4. CHEMOTHERAPY4. CHEMOTHERAPY4. CHEMOTHERAPY

Efficient-considered drugs: Efficient-considered drugs: adriamycin, cysplatinum, mytomycin Cadriamycin, cysplatinum, mytomycin C

a) SYSTEMICa) SYSTEMIC


b. b. LOCO-REGIONALLOCO-REGIONAL premise: locally administered cytostatic drugs are premise: locally administered cytostatic drugs are

more efficient than systemic administrationmore efficient than systemic administration11

repeatedly delivered by selective catheterization repeatedly delivered by selective catheterization through the femoral artery or through a catheter in through the femoral artery or through a catheter in the gastroduodenal artery (connected to a simple the gastroduodenal artery (connected to a simple reservoir or a pump)reservoir or a pump)

same cytostatic drugs as in systemic chemotherapy same cytostatic drugs as in systemic chemotherapy indications:indications:

non-resectable HCCnon-resectable HCC postresection recurrencespostresection recurrences HCC with indication for transplantationHCC with indication for transplantation22

1 1 ClavienClavien PA et al. – Surgery PA et al. – Surgery 20022002, 131, 433, 131, 4332 2 PoonPoon RT – Ann Surg RT – Ann Surg 2002 2002, 235, 466, 235, 466


c) c) CHCHEEMOEMBOLIZMOEMBOLIZATION ATION (TACE, TAOCE)(TACE, TAOCE)

combination of combination of embolizaembolization + tion + chcheemotmothheraperapy +y + Lipiodol Lipiodol // Lipiodol Lipiodol

&& Urografin Urografin (elective fixation in liver tumors, (elective fixation in liver tumors, “carriers” for the cytostatic drugs)“carriers” for the cytostatic drugs)

some authors contest the carrier role of some authors contest the carrier role of Lipiodol Lipiodol andand Urografin Urografin: these drugs don’t link : these drugs don’t link covalent bonds with the cytostatic drugscovalent bonds with the cytostatic drugs, , but but rather they form an emulsionrather they form an emulsion11

CLD – contraindication for chemoembolization CLD – contraindication for chemoembolization (it may decompensate the disease)(it may decompensate the disease) evaluation of the quality of the liver parenchyma evaluation of the quality of the liver parenchyma

before starting the treatmentbefore starting the treatment

1 1 ShermanSherman M M - - The GastroenterologistThe Gastroenterologist 19951995, 3, 55, 3, 55


despite the fact that theoretically the loco-despite the fact that theoretically the loco-regional methods of chemotherapy seem regional methods of chemotherapy seem attractiveattractive, , there isn’t yet an unanimous positive there isn’t yet an unanimous positive opinion over their role in the treatment of HCCopinion over their role in the treatment of HCC

the excellent results published by some authors the excellent results published by some authors could not be reproduced by otherscould not be reproduced by others

one-year survival followingone-year survival following ch cheemoembolizamoembolization is tion is reported between reported between 30-60%, 30-60%, higher than after higher than after systemic systemic chcheemotmothheraperapyy

none of the various methods of chemotherapy none of the various methods of chemotherapy (neoadjuvant or adjuvant), administered through (neoadjuvant or adjuvant), administered through different methods, significantly improve global or different methods, significantly improve global or „disease-free” survival„disease-free” survival11

1 Schwartz JD et al. - Lancet Oncol 2002, 3, 5931 Schwartz JD et al. - Lancet Oncol 2002, 3, 593


c) IMMUNOc) IMMUNOCHCHEEMOMOTHERAPYTHERAPY IIn n the last two decades: promising results the last two decades: promising results

offered byoffered by i immmunochmunocheemotmothheraperapyy1 1

Lymphokine-activated killer (LAK) cells andLymphokine-activated killer (LAK) cells and recombinant interleukin 2 (rIrecombinant interleukin 2 (rILL-2)-2) are infused are infused via a catheter in the splenic / gastroduodenal via a catheter in the splenic / gastroduodenal artery, together with aartery, together with a c cyytostatic tostatic drug drug (Doxorubicin) (Doxorubicin) in in emulsiemulsion of on of Lipiodol-Lipiodol-Urografin (substanUrografin (substancceess preferentially retained preferentially retained inin h hyypervascularizepervascularized liver tumorsd liver tumors) )

1 Okuno K et al. Cancer 1986, 58, 10011 Okuno K et al. Cancer 1986, 58, 10012 Lygidakis NJ et al. Hepatogastroenterology 2001, 48, 16852 Lygidakis NJ et al. Hepatogastroenterology 2001, 48, 16853 Kountouras J et al. Hepatogastroenterology 2002, 49, 11093 Kountouras J et al. Hepatogastroenterology 2002, 49, 1109


5. METHODS OF LOCAL 5. METHODS OF LOCAL ABLATIVE THERAPYABLATIVE THERAPY

5. METHODS OF LOCAL 5. METHODS OF LOCAL ABLATIVE THERAPYABLATIVE THERAPY


a) Percutaneous ethanol a) Percutaneous ethanol injection therapyinjection therapy

depending on liver function, percutaneous depending on liver function, percutaneous ethanol injection therapy (PEIT) can be ethanol injection therapy (PEIT) can be effective for small HCC effective for small HCC

advantage of repeated applicationsadvantage of repeated applications indicated in the case of small tumors indicated in the case of small tumors ((less less

thanthan 3 cm 3 cm diameter diameter) ) and of recurrencesand of recurrences11

the complete resolution of the tumors was the complete resolution of the tumors was noted in some studiesnoted in some studies2,32,3

recurrence raterecurrence rate 60% 60% 5-year survival rate 5-year survival rate 60%60%44

1 1 PoonPoon RT – Ann Surg RT – Ann Surg 2002 2002, 235, 466, 235, 4662 2 LeeLee MJ et al. – MJ et al. – AmAm JJ Roentgenol 1995Roentgenol 1995, 82, 122, 82, 122

3 3 LivraghiLivraghi T – T – World JWorld J Surg 1995Surg 1995, 164, 215, 164, 2154 4 ShiinaShiina S – S – AmAm JJ Roentgenol 1990Roentgenol 1990, 154, 947, 154, 947


Other forms of treatment currently are being Other forms of treatment currently are being under evaluationunder evaluation hyperthermic destructionhyperthermic destruction

microwavemicrowave radio-frequencyradio-frequency laserlaser

cryo-therapycryo-therapy they offer advantages similar to PEIT, they offer advantages similar to PEIT,

some of them without the need for some of them without the need for multiple sessionsmultiple sessions

all these forms of chemical or physical all these forms of chemical or physical ablation therapies may be associated with ablation therapies may be associated with different forms of chemotherapy, with different forms of chemotherapy, with increased efficiencyincreased efficiency11

1 1 LivraghiLivraghi T et al. – T et al. – Hepatogastroenterology Hepatogastroenterology 20022002, 49, 62, 49, 62


b) b) CrCryoablationyoablation

destruction by freezing at very low destruction by freezing at very low temperatures of non-resectable temperatures of non-resectable lesions:lesions: local invasionlocal invasion multiplicitymultiplicity

some preliminary results were some preliminary results were promisingpromising

limited by a significant morbiditylimited by a significant morbidity1,21,2

1 1 QueQue FG et al. – FG et al. – BrBr JJ Surg 1994Surg 1994, 81, 255, 81, 2552 2 HemmingHemming AW – AW – Br J SurgBr J Surg 1994 1994, 81, 1553, 81, 1553


c) Rc) Radiofreadiofrequency ablationquency ablation encouragingencouraging resultsresults11

the best results are achieved when performed the best results are achieved when performed intraoperativelyintraoperatively22, with, with direct control on the liver and iop USdirect control on the liver and iop US Pringle maneuver (diminishes the amount of heat Pringle maneuver (diminishes the amount of heat

“stolen” by the high blood stream through the tumor)“stolen” by the high blood stream through the tumor) RF may also be applied percutaneouslyRF may also be applied percutaneously

less side effectsless side effects less effective less effective

promising strategy for the treatment of larger promising strategy for the treatment of larger tumors: association of RF tumor destruction and tumors: association of RF tumor destruction and transarterial embolizationtransarterial embolization33

1 1 CurleyCurley SA et al. – Minerva Chir SA et al. – Minerva Chir 20022002, 57, 165, 57, 1652 2 MahviMahvi DM et al. – Ann Surg DM et al. – Ann Surg 1999 1999, 230, 9, 230, 93 3 PoonPoon RT – Ann Surg RT – Ann Surg 2002 2002, 235, 466, 235, 466


Other forms of therapyOther forms of therapy

irradiation with I-131 lipiodolirradiation with I-131 lipiodol irradiation with yttrium marked glass irradiation with yttrium marked glass

pelletspellets irradiation with I-131 tagged irradiation with I-131 tagged

antiferritin antibodiesantiferritin antibodies11

1 1 SitzmanSitzman JV et al. – Dig Surg JV et al. – Dig Surg 1995 1995, 12, 73, 12, 73


6. MINIMALLY INVASIVE 6. MINIMALLY INVASIVE SURGERYSURGERY

6. MINIMALLY INVASIVE 6. MINIMALLY INVASIVE SURGERYSURGERY

becomes more often used inbecomes more often used in pretherapeutic assessment (preresection, preTx)pretherapeutic assessment (preresection, preTx) treatment of CHCtreatment of CHC

laparoscopic US allowslaparoscopic US allows detection of lesions that have not been identified detection of lesions that have not been identified

preoperativelypreoperatively tumor biopsytumor biopsy guidance for interstitial ablative therapies guidance for interstitial ablative therapies

resection of small HCCs, located in resection of small HCCs, located in laparoscopic accessible liver segments, is also laparoscopic accessible liver segments, is also feasible feasible

1 Tait IS et al. – Br J Surg 2002, 89, 16132 Teramoto K et al. – Surg Endosc 2002, 16, 13633 Montorsi M et al. – Hepatogastroenterology 2002, 49, 56


Further progressFurther progressFurther progressFurther progress

wider use of screening to detect a wider use of screening to detect a larger proportion of treatable lesionslarger proportion of treatable lesions

strategies to prevent carcinogenesis strategies to prevent carcinogenesis in the cirrhotic liverin the cirrhotic liver

gene therapy to alter the tumor gene therapy to alter the tumor biologybiology


CENTER OF GENERAL SURGERY AND CENTER OF GENERAL SURGERY AND LIVER TRANSPLANTATIONLIVER TRANSPLANTATION

- Fundeni Clinical Institute –- Fundeni Clinical Institute –BucharestBucharest

January 1, 1995 – March 15, 2003January 1, 1995 – March 15, 2003556 liver resections556 liver resections

88 PATIENTS WITH HCC88 PATIENTS WITH HCCwith normal liverwith normal liver 52 cases (60%)52 cases (60%)with cirrhosiswith cirrhosis 36 cases (40%)36 cases (40%)


RESECTIONS IN NON-CIRRHOTIC RESECTIONS IN NON-CIRRHOTIC PATIENTSPATIENTS52 PATIENTS52 PATIENTS

Right hepatectomyRight hepatectomy 1717 Extended right hepatectomyExtended right hepatectomy 77

One case following ligation of the right portal branchOne case following ligation of the right portal branch Right lateral sectoriectomyRight lateral sectoriectomy 33 Left hepatectomyLeft hepatectomy 55 Extended left hepatectomyExtended left hepatectomy 22 Left lateral sectoriectomyLeft lateral sectoriectomy 33 Segmentectomy VIIISegmentectomy VIII 11 Non – anatomical resectionNon – anatomical resection 1414


January 2001

December 2000

Two-staged resection for HCC


1/2/2001 – Ligation of RPB

16 days following ligation


Volumetric assessment 2/02/2001 segm I-III 493 cm3, segm IV-VIII 1885 cm3 5/04/2001 segm I-III 515 cm3, segm IV-VIII 1055 cm3

8 weeks following ligation


Extended right hepatectomy specimen (+ segment IV), 8 weeks following ligature of the

right portal branch


1 Year postoperatively(april 2002)

Still alive, free of disease, in March 2003 (normal US)


AAssociated surgical procedures ssociated surgical procedures

resection of the diaphragmresection of the diaphragm 66 partialpartial resection of the inferior vena cava / resection of the inferior vena cava /

cavorrhaphycavorrhaphy 22 resection of thrombus from the portal veinresection of thrombus from the portal vein

11


DEBULKINGDEBULKING


ABDOMINAL CTABDOMINAL CTABDOMINAL CTABDOMINAL CT

a large, multinodular, dense, a large, multinodular, dense, slightly iodophyllic, imprecisely slightly iodophyllic, imprecisely delimited liver tumor localized delimited liver tumor localized in segments V+VIin segments V+VI

other disseminated other disseminated micronodular lesions in both micronodular lesions in both liver lobes – metastases ?liver lobes – metastases ?


SURGERYSURGERYSURGERYSURGERY

September 1999: September 1999: V+VI BISEGMENTECTOMYV+VI BISEGMENTECTOMYSeptember 1999: September 1999: V+VI BISEGMENTECTOMYV+VI BISEGMENTECTOMY

CITOREDUCTION CITOREDUCTION OF THEOF THE

PRIMITIVE TUMORPRIMITIVE TUMORMultiple disseminated tumors in the remaining RL and

in the LL, of different dimensions


Liver angiographyLiver angiographyLiver angiographyLiver angiography

Multiple hypervascularised zones

Permeability of the portal vein


TRANSARTERIAL OILY TRANSARTERIAL OILY CHEMOEMBOLIZATION (TAOCE)CHEMOEMBOLIZATION (TAOCE)

TRANSARTERIAL OILY TRANSARTERIAL OILY CHEMOEMBOLIZATION (TAOCE)CHEMOEMBOLIZATION (TAOCE)

doxorubicindoxorubicin 50 mg 50 mg dissolved in dissolved in

urografinurografin 5 ml 5 ml mixed with mixed with

lipiodollipiodol 5 ml 5 ml

November 1999: November 1999: November 1999: November 1999:

Injected in both liver Injected in both liver lobes through a catheter lobes through a catheter in the common hepatic in the common hepatic

artery artery (Seldinger technique)(Seldinger technique)


US-guided biopsy: HCC, G2

PERCUTANEOUS ETHANOL INJECTION


CT at 24 hours – complete tumoral

necrosis

CT at 1 month

CT at 8 months (June 2002)


July 2002July 2002

αFP – 350 IUCT – suspected

recurrence


September 2002September 2002Non-anatomical resection of 2nd recurrent tumor


Currently: alive and well, with no Currently: alive and well, with no signs of recurrence at signs of recurrence at 443 3 monthsmonths after the initial operationafter the initial operation


resection of hepatic recurrenceresection of hepatic recurrence 33 resection of extrahepatic recurrenceresection of extrahepatic recurrence 11

RESECTION OF RECURRENCESRESECTION OF RECURRENCES


II, m, 23February 1996: right hepatectomy February 1996: right hepatectomy + phrenectomy + phrenectomy + lymphadenectomy + lymphadenectomy

April 1997: atypical hepatectomyApril 1997: atypical hepatectomy

RE-RESECTION FOR RECURRENT HCC


MORBIDITY AND MORTALITY IN MORBIDITY AND MORTALITY IN PATIENTS WITH HCC ON NORMAL LIVERPATIENTS WITH HCC ON NORMAL LIVER

PostoperativePostoperative complicationscomplications DeathsDeaths

hepato – renal failurehepato – renal failure 11 11 biliary fistulabiliary fistula 33 pleuresypleuresy 22 hemoperitoneumhemoperitoneum 33 22 subphrenic abscesssubphrenic abscess 11 deep venous thrombophlebitisdeep venous thrombophlebitis 11 pulmonary abscess pulmonary abscess 11 11 subphrenic hematoma subphrenic hematoma 11 bronchopneumoniabronchopneumonia 11 11 acute heart failureacute heart failure 11 11 subhepatic abscesssubhepatic abscess 22 partial necrosis of parenchyma partial necrosis of parenchyma 11

40%40% 11%11%All deaths – before 1999


RESECTIONS IN CIRRHOTIC RESECTIONS IN CIRRHOTIC PATIENTSPATIENTS

36 patients36 patients

Left lateral sectoriectomyLeft lateral sectoriectomy 88 Left hepatectomyLeft hepatectomy 22 Right hepatectomyRight hepatectomy 44 Extended right hepatectomyExtended right hepatectomy 11 Right lateral sectoriectomyRight lateral sectoriectomy 22 Non – anatomical resectionsNon – anatomical resections 1919


MORBIDITY AND MORTALITY IN MORBIDITY AND MORTALITY IN PATIENTS WITH HCC ON CIRRHOSISPATIENTS WITH HCC ON CIRRHOSIS

PostoperativePostoperative complicationscomplications DeathsDeaths

choleperitoneumcholeperitoneum 11 11 haemoperitoneumhaemoperitoneum 33 22 bilateral pleuresy bilateral pleuresy 11 liver failureliver failure 1(4)1(4) 1(4)1(4) interhepatodiaphragmaticinterhepatodiaphragmatic hematoma and necrosishematoma and necrosis of the transection edgeof the transection edge 11 11

19%19% 14%14%All deaths – before 1999


Survival of patients with HCCSurvival of patients with HCC

30 months survival: > 60%30 months survival: > 60% 24 months survival: 30%24 months survival: 30%

HCC without cirrhosisHCC without cirrhosis HCC and HCC and cirrhosiscirrhosis

Time survival (months) Time survival (months)

Patie

nts s

till a

live

(%)

Patie

nts s

till a

live

(%)


LIVER TRANSPLANTATIONLIVER TRANSPLANTATION

2 CASES2 CASES 1 – recipient of a domino LTx from a 1 – recipient of a domino LTx from a

familial hypercholestoremia patientfamilial hypercholestoremia patient alive and well at 18 monthsalive and well at 18 months

1 – HCC on VHC cirrhosis - recipient of the 1 – HCC on VHC cirrhosis - recipient of the right side of a split LTxright side of a split LTx alive at 5 months; recurrent VHC hepatitisalive at 5 months; recurrent VHC hepatitis

both patients were submitted to both patients were submitted to chemoembolisation prior to LTxchemoembolisation prior to LTx


RESECTED SPECIMEN IN PATIENT 1

RESECTED SPECIMEN IN PATIENT 2


LOCAL INTERSTITIAL LOCAL INTERSTITIAL THERAPIESTHERAPIES

June 1, 2001 – March 15, 2003June 1, 2001 – March 15, 2003

13 PATIENTS13 PATIENTS

IMIM 1010 PMPM 99 IRFIRF 44 PRFPRF 2 2

IM – intraoperative MWIM – intraoperative MWPM – percutaneous MWPM – percutaneous MWIRF – intraoperative RFIRF – intraoperative RFPRF – percutaneousPRF – percutaneous RF


CONCLUSIONSCONCLUSIONS

Treatment of HCC is at present time Treatment of HCC is at present time multimodalmultimodal

In non-cirrhotic patients resection is the In non-cirrhotic patients resection is the preferred treatmentpreferred treatment

In cirrhotic patients liver transplantation In cirrhotic patients liver transplantation seems to be the best treatment optionseems to be the best treatment option

If LTx is unavailable, other alternative If LTx is unavailable, other alternative tumor ablative treatments (MW, RF, PEIT) tumor ablative treatments (MW, RF, PEIT) should be usedshould be used

ENDEND

document22

Health & Medicine

palliative reduction

hepatocellular carcinoma

treatmentresistant hcc

standardizedthe treatment

selected patients

severe patients

preferred method of

behalf of hcc