2. 2
ΗΠΑΤΟΚΥΤΤΑΡΙΚΟΣ ΚΑΡΚΙΝΟΣ
Το 2010 κατεγράφησαν 21370 περιστατικά ΗΚΚ στις ΗΠΑ
>75% αύξηση από το 1993
Το 2010 υπήρξαν 18410 θάνατοι από ΗΚΚ στις ΗΠΑ
- 5η
Αιτία θανάτου από καρκίνο στους άνδρες
1ετής επιβίωση μεταξύ 22% – 32%
5ετής επιβίωση μόνον 8% - 13%
Daniel Cherqui, et al. Surg Oncol Clin N Am 2008
3. 3
Natural history of HCC (n=102)
0
20
40
60
80
100
0 12 24 36 48 60 72
Probability(%)
months
Patients at risk 102 57 40 21 8
Median survival: 17m
Number of deaths: 79 patients
54%
40%
28%
Llovet JM, et al. Cancer 2003; 362: 1907-17.
Hepatocellular CancerHepatocellular Cancer
7%
4. 4
ΗΠΑΤΟΚΥΤΤΑΡΙΚΟΣ ΚΑΡΚΙΝΟΣ
Χειρουργική αντιμετώπιση: Η Μόνη Αποτελεσματική Θεραπεία
< 30% συνήθως λόγω πολυεστιακής ή μεταστατικής νόσου
Στο 90% συνυπάρχει χρόνια ηπατοπάθεια - κίρρωση
Σε ΗΚΚ χωρίς κίρρωση → Χειρουργική εκτομή
Σε ΗΚΚ με κίρρωση → Μεταμόσχευση ήπατος
Freeman RB Jr. Liver Transplantation 2006
Yao FY, et al. Liver Transplantation 2002
6. 6
ΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΧΩΡΙΣΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΧΩΡΙΣ
ΧΡΟΝΙΑ ΗΠΑΤΟΠΑΘΕΙΑΧΡΟΝΙΑ ΗΠΑΤΟΠΑΘΕΙΑ
10% του συνόλου των ΗΚΚ
Ιστολογικώς «υγιές» ήπαρ
Ινοπεταλιώδες ΗΚΚ:
Νεαρές γυναίκες 20 – 40 ετών
Αριστερός λοβός
Φυσιολογική alpha-fetoprotein
Πρώιμη λεμφαδενική διασπορά
Έλλειψη screening
Καθυστερημένη διάγνωση
Ευμεγέθεις > 10 εκ – Συμπτωματικοί όγκοι
CT – MRI scan
Lau WY, et al. Hepatobiliary Pancreat Dis Int 2008
Poon RT, et al. Arch Surg 2004
7. 7
ΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΧΩΡΙΣΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΧΩΡΙΣ
ΧΡΟΝΙΑ ΗΠΑΤΟΠΑΘΕΙΑΧΡΟΝΙΑ ΗΠΑΤΟΠΑΘΕΙΑ
Θεραπεία εκλογής: Ηπατεκτομή
5ετής επιβίωση 50%
Ο ρόλος της μεταμόσχευσης είναι περιορισμένος λόγω:
1. Του προχωρημένου σταδίου κατά τη διάγνωση
2. Του αυξημένου κινδύνου υποτροπής
Αντενδείξεις:
Απόλυτη: Εξωηπατική Νόσος
Σχετικές: Πολλαπλές βλάβες και στους 2 λοβούς
Διήθηση του χοληδόχου πόρου
Θρόμβωση PV – IVC
Belghiti J, et al. HPB 2005
El-Serag HB, et al. Hepatology 2004
13. 13
Resection for HCCResection for HCC
Survival (%)
Author N 1-year 5-year
Takayama ’98 52 92 54
Fong ’99 (<5 cm) 100 83 42
Llovet ’99 (<5 cm) 35 85 51
Arii ’00
<3 cm 767 96 54
3–5 cm 587 95 38
Zhou ’01 1000 62
Poon ’02 161 79 44
Ikai ’04
<3 cm(10%) 2320 83 66
3–5 cm 5956 70 53
5–10 cm 1946 53 37
>10 cm 819 44 32
Data from Llovet JM et al. Semin Liver Dis. 2005;25:181-200.
14. 14
Study n 1 yr 3 yrs 5 yrs
Sasaki, 1987 101 30 64 70
Belghiti, 1991 47 42 81 100
Capussotti, 1994 33 32 64 88
Yamamoto, 1996 229 20 70 83
Fuster, 1996 48 22 47 -
Chiappa,2000 51 45 96 -
Grazi, 2001 264 - 36 56
Poon,2002 135* 24 48 60
% recurrence after
Recurrence after liver resection forRecurrence after liver resection for
hepatocellular carcinoma in cirrhotichepatocellular carcinoma in cirrhotic
patientspatients
Data from Llovet JM et al. Semin Liver Dis. 2005;25:181-200.
15. 15
ΥΠΟΤΡΟΠΗ ΜΕΤΑ ΕΚΤΟΜΗ ΗΚΚΥΠΟΤΡΟΠΗ ΜΕΤΑ ΕΚΤΟΜΗ ΗΚΚ
Υποτροπή:
- 78%-96% στην 5ετία
- Ενδοηπατικές μεταστάσεις
α. Μέγεθος > 5 εκ
β. Child Grade B - C
γ. Χαμηλή διαφοροποίηση
δ. Μη-ανατομική εκτομή
ε. Δορυφόρες εστίες
στ. Διηθητικός χαρακτήρας
ζ. Μεταγγίσεις αίματος
Αντιμετώπιση της υποτροπής:
Re-resection?
Percutaneous RF Ablation?
TACE?
Salvage Transplantation? Belghiti J, et al. HPB 2005
16. 16
Barcelona Clinic Liver Cancer (BCLC) stagingBarcelona Clinic Liver Cancer (BCLC) staging
classification and treatment scheduleclassification and treatment schedule
Llovet, J. M. et al. J. Natl. Cancer Inst. 2008 100:698-711
19. 19
0 20 40 60 80 100
100
90
80
70
60
50
40
30
20
10
Time (months)
SurvivalfromListing(%)
2790 2092 1618 1311 1199
346 169 140 55 55
Patients at Risk
P<.0001
Within Milan
Exceed Milan
Data from Pelletier SJ et al. Liver Transpl. 2009;15:859-868.
Overall Survival in Transplant for HCC
20. 20
ΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΣΕ ΧΡΟΝΙΑΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΣΕ ΧΡΟΝΙΑ
ΗΠΑΤΟΠΑΘΕΙΑ - ΚΙΡΡΩΣΗΗΠΑΤΟΠΑΘΕΙΑ - ΚΙΡΡΩΣΗ
Δεν υπάρχουν RCTs για Resection vs Transplantation
α. Η μεταμόσχευση αφαιρεί τον όγκο και την προνεοπλασματική
υποκείμενη ηπατοπάθεια
β. Θεραπεία εκλογής για μικρούς όγκους χωρίς αγγειακή
διήθηση
γ. Περιορισμένα Κριτήρια Επιλογής
δ. Έλλειψη Μοσχευμάτων
ε. 25% Drop-out από τη λίστα
στ. Αναμονή > 6-10 μήνες → κανένα όφελος στην επιβίωση
ε. Υψηλό κόστος - Δεν είναι πάντοτε διαθέσιμη
Yao FY, et. Liver Transpl 2006
22. 22
ΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΣΕ ΧΡΟΝΙΑΗΠΑΤΕΚΤΟΜΗ ΓΙΑ ΗΚΚ ΣΕ ΧΡΟΝΙΑ
ΗΠΑΤΟΠΑΘΕΙΑ - ΚΙΡΡΩΣΗΗΠΑΤΟΠΑΘΕΙΑ - ΚΙΡΡΩΣΗ
HH ηπατεκτομή ΔΕΝ «ανταγωνίζεται» τη μεταμόσχευσηηπατεκτομή ΔΕΝ «ανταγωνίζεται» τη μεταμόσχευση
Η προηγηθείσα εκτομή δεν μειώνει τους συντελεστές επιβίωσης τηςΗ προηγηθείσα εκτομή δεν μειώνει τους συντελεστές επιβίωσης της
μεταμόσχευσηςμεταμόσχευσης
Ηπατεκτομή ως αρχική θεραπεία:
1. Η1. Η LTLT μπορεί να ακολουθήσει σε υποτροπή ή ηπατικήμπορεί να ακολουθήσει σε υποτροπή ή ηπατική
ανεπάρκειαανεπάρκεια
2.2. Για την καλύτερη επιλογή ασθενών γιαΓια την καλύτερη επιλογή ασθενών για LTLT με βάση ταμε βάση τα
χαρακτηριστικά του όγκου και του γειτονικού παρεγχύματοςχαρακτηριστικά του όγκου και του γειτονικού παρεγχύματος
3.3. Ηπατεκτομή “as a bridge to transplantation”
Belghiti J. J Gastroenterol 2009; 44: 132-5Belghiti J. J Gastroenterol 2009; 44: 132-5
26. 26
Survival Following Resection for HCCSurvival Following Resection for HCC
Best candidates for resectionBest candidates for resection :: - Solitary HCC<5cm- Solitary HCC<5cm
- Child-Pugh A- Child-Pugh A
No Portal HypertensionNo Portal Hypertension
Normal BilirubinNormal Bilirubin
0
20
40
60
80
100
0 12 24 36 48 60 72 84 96
No portal hypertension<10mmHg (n= 35)
Portal hypertension and normal bilirubin (n=15)
Portal hypertension and Bilirubin >1 mg/dL (n=27)
Log Rank 0.00001
Survival(%)
months
74%
50%
25%
Rampone B, et al. World J Gastroenterol 2009
3-year recurrence: 50%
27. 27
Preoperative Assessment of Liver FunctionPreoperative Assessment of Liver Function
Test Author Contraindication for Resection
ChildPughTurcotte Franco Score > 8, Score B - C
Serum alanine transferase
clearance ICG
Noun ALT > twofold upper limit of norm
Indocyanine green
Makuuchi 1. retention rate at 15 minutes < 15 %
Μείζονα Ηπατεκτομή >3segments
2. retention rate at 15 minutes > 15 %
Περιορισμένη εκτομή <3segments
Urea nitrogen synthesis Paqu < 6 g/day
Portal Vein Pressure Bruix HVPG > 10mm Hg
Lidocaine (MEGX) test Ercolani G MEGX <25 ng/ml*
Grazi MEGX <25 ng/ml*
28. 28
Normal Portal Vein Post Embolization
Left
Right
Left
Right
Anticipated liver remnant
Pre-operative Portal Vein EmbolizationPre-operative Portal Vein Embolization
29. 29
Preoperative InterventionsPreoperative Interventions
Πρόληψη Αιμορραγίας των κιρσών τουΠρόληψη Αιμορραγίας των κιρσών του
οισοφάγουοισοφάγου
– Sclerotherapy/bandingSclerotherapy/banding
– Transjugular intrahepaticTransjugular intrahepatic
portosystemic shunt (TIPS)portosystemic shunt (TIPS)
HA Embo: Chemo (TACE) or bland TAE)HA Embo: Chemo (TACE) or bland TAE)
– Μειώνει το μέγεθος του όγκουΜειώνει το μέγεθος του όγκου
– Υποσταδιοποίηση?Υποσταδιοποίηση?????
– Αντιμετώπιση αιμορραγίας απόΑντιμετώπιση αιμορραγίας από
αυτόματη ρήξηαυτόματη ρήξη
– Μπορεί να συνδυαστεί μεΜπορεί να συνδυαστεί με PVEPVE
Umbilical V.
Varices
30. 30
ΚΡΙΤΗΡΙΑ ΕΠΙΛΟΓΗΣ ΓΙΑ ΧΕΙΡΟΥΡΓΙΚΗ
ΕΚΤΟΜΗ ΗΚΚ ΣΕ ΧΡΟΝΙΑ ΗΠΑΤΟΠΑΘΕΙΑ
Μείζονα Ηπατεκτομή (Ηπατεκτομή (≥ 3 τμήματα)≥ 3 τμήματα)::
1. Child-Pugh class A (έως 50%)
2. ICG retention 15min < 15%
3. Απουσία κιρσών οισοφάγου στην ενδοσκόπηση
4. Αιμοπετάλια >100 000/mm3
5. ALT/AST ≤ διπλάσιο του φυσιολογικού
6. Υπερτροφία του αντίπλευρου λοβού μετά από PVE
7. Functional residual volume ≥ 50% - CT volumetry -
(FRV= Total liver volume – [resected volume-tumor volume])
Περιορισμένη Ηπατεκτομή (< 3 τμήματα):
1. Child-Pugh class A
2. Child-Pugh class B για περιφερική ογκεκτομή (έως 25%)
Pawlik TM, et al. Arch Surg 2005
Schwartz JD, et al. Lancet Oncol 2002
Poon RT, et al. Ann Surg 2002
31. 31
ΧΕΙΡΟΥΡΓΙΚΗ ΕΚΤΟΜΗ ΓΙΑ ΗΚΚ
ΒΑΣΙΚΕΣ ΑΡΧΕΣ
Διατήρηση του Ηπατικού
παρεγχύματος
Ανατομική Ηπατεκτομή
Έλεγχος της αιμορραγίας
32. 32
ΧΕΙΡΟΥΡΓΙΚΗ ΕΚΤΟΜΗ ΓΙΑ ΗΚΚ
ΤΕΧΝΙΚΕΣ ΔΥΣΚΟΛΙΕΣ
Όριο Εκτομής ~ 1εκΌριο Εκτομής ~ 1εκ
Σκληρό παρέγχυμαΣκληρό παρέγχυμα
Αλλοίωση των ανατομικώνΑλλοίωση των ανατομικών
οδηγών σημείωνοδηγών σημείων
Ευθραυστότης των ιστώνΕυθραυστότης των ιστών
Αδυναμία διάκρισης του όγκουΑδυναμία διάκρισης του όγκου
από το περιβάλλον κιρρωτικόαπό το περιβάλλον κιρρωτικό
ήπαρήπαρ
41. 41
ΧΕΙΡΟΥΡΓΙΚΗ ΕΚΤΟΜΗ ΓΙΑ ΗΚΚ
ΔΙΕΓΧΕΙΡΗΤΙΚΕΣ ΕΚΤΙΜΗΣΕΙΣ
Πλήρης απεικονιστική αξιολόγησηΠλήρης απεικονιστική αξιολόγηση
((MRI – CT volumetryMRI – CT volumetry))
Καρδιοαναπνευστικός έλεγχος (>65Καρδιοαναπνευστικός έλεγχος (>65
ετών)ετών)
Μετάγγιση αυτολόγου αίματοςΜετάγγιση αυτολόγου αίματος
Δεξιά υποπλεύριος ή τομήΔεξιά υποπλεύριος ή τομή JJ ήή
αμφιπλεύριος τύπουαμφιπλεύριος τύπου ChevronChevron
α. Ευρεία έκθεσηα. Ευρεία έκθεση
β. Έλεγχος περιτοναικής κοιλότηταςβ. Έλεγχος περιτοναικής κοιλότητας
γ. Χρήσηγ. Χρήση IOUSIOUS
Makuuchi M, et al. Oncology 2002
42. 42
ΧΕΙΡΟΥΡΓΙΚΗ ΕΚΤΟΜΗ ΓΙΑ ΗΚΚ
ΕΓΧΕΙΡΗΤΙΚΕΣ ΑΡΧΕΣ
Χαμηλή CVP < 5 εκ H2O
Ασθενής σε θέση Trendelenburg 15°
- Διεκολύνει την παρασκευή της IVC
- Μειώνει την αιμορραγία από τις ηπατικές φλέβες
- Μειώνει τον κίνδυνο εμβολής από αέρα
Ανατομικές εκτομές / Τμηματικές εκτομές υπό IOUS
Αγγειακός έλεγχος:
- Inflow control (extraGlissonian Pringle, pedicle ligation)
- Eξωηπατικός αποκλεισμός των ηπατικών φλεβών
- Anterior Approach – Hanging maneuver
Belghiti J. J Gastroenterol 2009
Makuuchi M, et al. Liver Transpl 2004
43. 43
ΧΕΙΡΟΥΡΓΙΚΗ ΕΚΤΟΜΗ ΓΙΑ ΗΚΚ
ΕΓΧΕΙΡΗΤΙΚΕΣ ΑΡΧΕΣ
Intermittent portal triad clamping (Pringle maneuver): 90min
Ischemic Preconditioning
Parenchymal transection:
- Kelly clamp (crash-clamp technique)
- CUSA
- Vascular staplers
- Tissue link
- Water-jet dissection
- Harmonic scalpel (κίρρωση, λαπαροσκοπική ηπατεκτομή)
- Radiofrequency energy
Παροχετεύσεις υπό συνθήκες (χολοπεπτική αναστόμωση, επίμονη
χολόρροια, μολυσμένη επέμβαση, εκτομή διαφράγματος)
Abdalla EK, et al. Surg Clin North Am 2004
46. 46
RADIOFREQUENCY ABLATIONRADIOFREQUENCY ABLATION
Minimally InvasiveMinimally Invasive
Can be therapeutic in some casesCan be therapeutic in some cases
““Bridge” to transplantationBridge” to transplantation
BUT!!!BUT!!!
High Local RecurrenceHigh Local Recurrence
Tumor DisseminationTumor Dissemination
Not All Sizes or Locations PossibleNot All Sizes or Locations Possible
Operator DependentOperator Dependent
48. 48
Hepatic Resection: Early ResultsHepatic Resection: Early Results
Operation Operative Mortality
Trisegmentectomy 25% (10/40)
Lobectomy 21% (49/230)
L. Lateral Segmentectomy 7% (5/69)
Wedge Resection 6% (18/282)
---------------------------------------------------------
Total 13% (82/621)
Foster JH, Berman MM. Major Problems in Clinical Surgery 1977;1-342.
49. 49
Hepatic Resection in CirrhoticHepatic Resection in Cirrhotic
Livers: The Early ViewLivers: The Early View
“…Partial hepatectomy for tumors
occurring in cirrhotic livers should not be
done unless it is necessary to control
hemorrhage.”
•Liver Tumor Survey-- 1974
- Mortality rate was 58% in cirrhotic
patients (n =26).
Foster JM, Berman MM,. Solid Liver Tumor,1977;p. 62-104
52. 52
ΠΡΟΓΝΩΣΤΙΚΟΙ ΠΑΡΑΓΟΝΤΕΣ ΕΠΙΒΙΩΣΗΣΠΡΟΓΝΩΣΤΙΚΟΙ ΠΑΡΑΓΟΝΤΕΣ ΕΠΙΒΙΩΣΗΣ
FactorFactor FavorableFavorable UnfavorableUnfavorable
Child-Pugh classChild-Pugh class AA BB
BilirubinBilirubin NormalNormal ElevatedElevated
Severity of FibrosisSeverity of Fibrosis No CirrhosisNo Cirrhosis CirrhosisCirrhosis
Portal HypertensionPortal Hypertension AbsentAbsent PresentPresent
Hepatitis activityHepatitis activity NormalNormal > Two times normal> Two times normal
Tumor factorsTumor factors
SizeSize < 2-3 cm< 2-3 cm > 5 cm> 5 cm
NumberNumber SingleSingle Multiple, bilobarMultiple, bilobar
Vascular invasionVascular invasion AbsentAbsent PresentPresent
DifferentiationDifferentiation Well differentiatedWell differentiated Poorly differentiatedPoorly differentiated
Satellite nodulesSatellite nodules AbsentAbsent PresentPresent
AFPAFP NormalNormal > 1000> 1000
Surgical factorsSurgical factors
MarginMargin > 1 cm> 1 cm < 1 cm< 1 cm
Type of resectionType of resection AnatomicAnatomic NonanatomicNonanatomic
Blood transfusionBlood transfusion AbsentAbsent PresentPresent
53. 53
Hepatic Segmental AnatomyHepatic Segmental Anatomy
Couinaud’s Segments of the LiverCouinaud’s Segments of the Liver
Couinaud C. Lobes des segments hepatiques: notes sur architecture anatomique
et chirurgicale du foie.
Presse Medicale 1954: 62: 709-12.
56. 56
Anatomically Based SegmentalAnatomically Based Segmental
ResectionsResections
Greater technical flexibility
•Less extensive resections in patients with limited disease
•Bilateral resections in patients with multiple tumors
66. 66
LAPAROSCOPIC LIVER RESECTION FOR HCCLAPAROSCOPIC LIVER RESECTION FOR HCC
Cherqui D, et al. Ann Surg 2007Tumor Size < 5 cm
Liver Segments II - VI
67. 67
LAPAROSCOPIC LIVER RESECTION FOR HCCLAPAROSCOPIC LIVER RESECTION FOR HCC
“BRIDGE” TO TRANSPLANTATION“BRIDGE” TO TRANSPLANTATION
68. 68
LAPAROSCOPIC LIVER RESECTION FOR HCCLAPAROSCOPIC LIVER RESECTION FOR HCC
LIVING DONOR LIVER TRANSPLANTATIONLIVING DONOR LIVER TRANSPLANTATION
70. 70
ΣΥΜΠΕΡΑΣΜΑΤΑΣΥΜΠΕΡΑΣΜΑΤΑ
Η χειρουργική αντιμετώπιση είναι η θεραπεία εκλογήςΗ χειρουργική αντιμετώπιση είναι η θεραπεία εκλογής
Σε ΗΚΚ χωρίς κίρρωσηΣε ΗΚΚ χωρίς κίρρωση::
- Μείζονα ηπατεκτομή- Μείζονα ηπατεκτομή
- Καλά ποσοστά επιβίωσης (- Καλά ποσοστά επιβίωσης (≥ 10εκ)≥ 10εκ)
- Μικρός εγχειρητικός κίνδυνος- Μικρός εγχειρητικός κίνδυνος
Σε ΗΚΚ με υποκείμενη κίρρωσηΣε ΗΚΚ με υποκείμενη κίρρωση::
- Επιλογή ασθενών- Επιλογή ασθενών
- Επαρκής ηπατική λειτουργία- Επαρκής ηπατική λειτουργία
- Ανατομική ηπατεκτομή- Ανατομική ηπατεκτομή
- Διατήρηση του παρεγχύματος- Διατήρηση του παρεγχύματος
- Μείωση της αιμορραγίας- Μείωση της αιμορραγίας
- Νοσηρότης < 5% - 5ετής επιβίωση 50% - 70%- Νοσηρότης < 5% - 5ετής επιβίωση 50% - 70%
- Μπορεί να συνδυαστεί με Μεταμόσχευση- Μπορεί να συνδυαστεί με Μεταμόσχευση
Editor's Notes
&lt;number&gt;
The prognosis for hepatocellular cancer for the last two decades is reported to be dismal. Most patients have died within one year of diagnosis. In developed countries that prognosis has increased significantly. Up to 40% of patients are now being diagnosed early.
One prospective study from Barcelona examined the natural history of 102 patients who had hepatocellular cancer which was not felt to be amenable to surgery. At the end of the study they had 79 deaths. Survival rates for 1 year, 2 years, and 3 years were 54, 40, and 28 %, respectively. The researchers concluded that prognosis for cancer in nonsurgical cases overall is dismal, but that there seem to be subgroups of patients who have a better prognosis, and whose cancer seems to not be as biologically aggressive.
&lt;number&gt;
Surgical resection is also the treatment of choice for the unusual patient with primary liver cancer but no evidence of cirrhosis, and surgery may be these patients’ only chance for survival.
One problem with surgical resection of liver cancer is that the majority of patients whom we see have varying degrees of underlying cirrhosis, often with significant intra-abdominal variceal formation, splenomegaly, and severe levels of thrombocytopenia. All of these factors limit our being able to perform aggressive treatments. Consequently, the majority of our patients would not tolerate surgical resection of their liver cancer.
&lt;number&gt;
In terms of recurrence after liver resection for hepatocellular cancer in cirrhotic patients, it has been established that coexisting cirrhosis has a significant effect on recurrence rate. Until recently, the recurrence rates have been as high as 70 to 100%. In 1996, Yamamoto described one of the most important factors in predicting recurrence was the coexisting cirrhosis.
It may be that this high effect is due to the carcinogenic effect of the cirrhosis, or that there were sub-clinical tumors at the time of the resection. Regardless, with improved patient selection, that recurrence rate has decreased somewhat.
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In a study out of Europe, where they studied patients with hepatocellular cancer, they found that the best candidates for resection were those who had solitary tumors and those who had Child-Pugh score or A, with no portal hypertension and a normal bilirubin. The 5-year survival rate was 74%. In the presence of portal hypertension, at 5-years, with normal bilirubin, that decreased to 50%. And with portal hypertension and an elevated bilirubin, that decreased to 25%.
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Most surgeons will consider resection of a cancer in a patient with Child-Pugh functional status of A. The problem is figuring out which patients in the A classification will go on to develop post-operative liver failure.
This slide shows different metabolic tests which were developed in an attempt to quantify liver function better than the Child-Pugh scoring system. The Japanese use substrate dyes which are injected into patients, metabolized by the liver, and then can be measured afterwards. Indocyanine green clearance by the liver is used in Japan to select the best patients for surgery. In Europe they measure the direct hepatic vein-portal vein pressure gradient (HVPG), along with serum bilirubin, to select the best patients. More recently, some surgeons have been looking at the metabolites of lidocaine, which can be measured after the lidocaine is injected intravenously.
It’s important to recognize that none of these tests, although they’ve been shown to discriminate between Child’s A, B, and C status, is yet accepted as a standard measure in the United States. We routinely use the Child-Pugh scoring system to sort out the best surgical patients.
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A more recent preoperative intervention is this portal vein embolization. It was just introduced in the last decade.
In patients with cirrhosis the most important aspect of surgical resection is to obtain a clear histologic margin while at the same time try to maintain as much functional liver parenchyma as possible.
In certain situations you might have a patient who has otherwise resectable cancer, but someone may actually relegate these patients to non-surgical treatments because of fear of post-operative liver failure.
Preoperative portal vein embolization was introduced to minimize that risk. For this technique, you introduce a catheter percutaneously into the right portal vein if the tumor is on the right side--you embolize the portal vein on the same side of the liver, occluding portal blood supply to that area. The idea is that you induce hypertrophy of the other side of the liver, which gives you more viable liver after your resection. You do this 4-6 weeks prior to the planned operation to minimize the risk of postoperative liver failure.
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There are some preoperative interventions that can be performed to improve the margin of safety in operating on the liver of a patient with cirrhosis.
Following liver resection, some patients can develop postoperative GI bleeding because they have an increase in their portal hypertension. Depending on specific anatomical considerations of the surgery, individual sites of bleeding, such as from a recanalized paraumbilical vein, can occur.
As a result, some surgeons recommend that all of their patients undergo preoperative endoscopy and, if they have medium- or large-sized varices, that they undergo endoscopic band or sclerosant obliteration of the varices.
Some surgeons also favor placement of a preoperative TIPS shunt prior to abdominal surgery. We believe that patients who have such severe portal hypertension that they may require placement of a TIPS may ultimately have their cancer better managed by liver transplantation or non-operative techniques.
Occasionally some groups will also use hepatic arterial embolization as a preoperative intervention to decrease tumor bulk to try to make the operation easier. This actually can make a difference.
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In a study from Memorial Sloan-Kettering in New York, 267 patients who underwent liver resections for cancer were reviewed. There were 119 patients who underwent wedge resection and 148 patients who underwent segmental hepatectomy. The positive margins in the wedge resections were 16%, compared to 2% in the patients who underwent segmental hepatectomy. So sticking to anatomical boundaries when possible is a good approach.
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We’ve learned from our experience with metastatic colorectal cancer that anatomically based segmental resections are superior to wedge resections, since they are associated with less intraoperative blood loss, better tumor removal, and improved overall survival.
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I’m going to focus more on the technical aspects of liver surgery.
It was in 1952 that Lortat-Jacob first described the anatomic lobectomy. It was this event that ushered in the era of modern hepatic surgery. Unfortunately, subsequent events were not encouraging.
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In 1977 Berman and Foster reported on a multi-center experience with 621 patients who underwent removal of various segments of the liver, with an overall operative mortality rate of 13%, extending up as high as 25%. Over 20% of these mortalities occurred as a result of intraoperative hemorrhage.
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The results for resection in cirrhotic patients is even more discouraging.
Again, in 1977, in Solid Liver Tumor, edited by Foster and Berman, it was stated that “Partial hepatectomy for tumors occurring in cirrhotic livers should not be done unless it is necessary to control hemorrhage.”
This came from data from the 1974 Liver Tumor Survey, where they observed a mortality of 58% of hepatic resection in cirrhotic patients.
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Fortunately, the operative mortality rate for liver resection has decreased significantly over the last 2 decades, and it is now lower than 5% in high-volume centers.
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Similar results have been seen for patients undergoing hepatic resection for hepatocellular carcinoma. In the 1980s the mortality rate was as high as 30%; it’s now consistently less than 10%.
In 1999, Fong and collaegues reported on 100 patients who underwent resection of hepatomas, and the overall operative mortality rate was 5%, and the 5-year actuarial survival was 37%.
In Japan, with improved patient selection in the Liver Cancer Study Group, they’ve demonstrated that you can achieve survival rates as high as 75%. These improvements in overall surgical results for patients undergoing liver resection result from better patient selection, but also improvements in general anesthesia and improvements in general surgical techniques, and the development of hepatobiliary surgery as a specialty.
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Perhaps one of the most important aspects of this is the development of hepatic segmental anatomy. The concept now is hat we can actually remove individual segments of liver.
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In a normal liver, in patients who don’t have underlying cirrhosis, it’s possible to remove up to 80% of the liver, either with an extended right hepatectomy or a left extended hepatectomy, leaving in either case only 2 functional segments. With patients who have cirrhosis, most surgeons are hesitate to resect more than 2 functional segments.
Fortunately, we’ve shown that segmental resections are equivalent to classic lobar resections, without the need for removing large amounts of functioning liver.
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These anatomically based segmental resections offer greater technical flexibility. They allow you to perform less extensive resections in patients who have small or limited disease, or who have underlying cirrhosis.
And they allow you to do bilateral resections in patients who have multi-lobar disease.
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This is an example of a patient who underwent a resection of segment II, shown in black in the diagram above. And this is an intraoperative photograph showing the resection margin.
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This is another anatomically based segmental resection. This is resection of segment VII and segment VI (shown in black above). It’s called a posterior segmentectomy. This is the preferred approach for patients who have tumors localized just behind the right hepatic vein or posterior to the right hepatic vein.
The intraoperative photo of the resection is also shown.