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Massimo Malago 2
Massimo Malago 2
Massimo Malagó
The Ilse Bagel Professor of Surgery and
Transplantation
University of Duisburg-Essen
Resection AND / OR
Transplantation
Radicality Organ preservation, I/R
Preserved function Immunology
Multidisciplinarity
Cooperation
Oncology, RT, nutrition Hepatology, ICU, virolog
No Competition but
Sinergy!!!!
General Survey
Indications - Results
Organ allocation
Immunosuppression
www.eltr.org/publi/results.
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www.eltr.org/publi/results.
* Others : Budd Chiari : 567 Benign liver tumors or Polycystic diseases : 635
Parasitic
Klinik diseases
für Allgemein-, : 54und Transplantationschirurgie,
Viszeral- Other liver diseases : 523
Universitätsklinikum Essen
Primary Diseases leading to Liver Transplantion by Country
01/1988 - 12/2005
AUSTRIA
BELGIUM
CZECH REP.
DENMARK
FINLAND
FRANCE
GERMANY
GREAT BRITAIN
HUNGARY
Cirrhosis : 33845
IRELAND
ITALY Acute hepatic failure : 5166
MONACO
Cancers : 7318
NETHERLANDS
NORWAY Others : 7166
POLAND
PORTUGAL
ROMANIA
SLOVENIA
SPAIN
SWEDEN
SWITZERLAND
TURKEY
YUGOSLAVIA
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
0% 20% 40% 60% 80% 100%
Liver transplantation in liver tumors
other than HCC
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www.eltr.org/
publi/results.
Donor risks!!
Recipients: suboptimal results in
- advanced tumors
- severe cirrhosis
Liver Transpl. 2001 7:9217
80%
60%
40%
20%
0%
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ECD
Marginal SPLIT Living Donor
donors
Domino
General Survey
Indications - Results
Organ allocation
Immunosuppression
Liver transplantation
Vs
Liver resection
Hemihepatektomie 892
Erweiterte Hemihepatektomie 308
Anatomische Leberresektionen 341
Nicht-anatomische Leberresektionen 937
Hepatikusgabelresektionen 58
Leberlebendspender 174
___________
Leberresektionen
gesamt 2710
(HCC)
Hepatoblastoma
CCC
neuroendocrine (NE)
Metastatic tumors
non NE Colorectal
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
LTX ESSEN April 1998 – October 2006
n = 881
Reduced Liver (8)
LDLT (185)
Split (115)
Standard-Tx (573)
37
53
1 61 148
7 46
ALDLT n =148
528 8
Right
Left
140
54 1
42
hcc
hcc
other tumors
other tumors
other disease
other disease
73
7 475
AdenoCa
2 1 Hepatoblastoma HCC
50
Pseudo-Tumor
51 Mesenchymal
123 2
NeuroEndocrine
Non Tumor
HCC Mesenchymal
AdenoCa
4 56 14 NeuroEndocrine
LDLT n=1
Hilar (Klatskin-Tumor)
without cirrhosis, without PSC *
with PSC
*normal liver functional reserve
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
Cholangiocarcinoma
- without cirrhosis, without PSC
Extended Liver Resections
Berdah/1996 19 67 40 32 15
Chu/1997 39 57 24 16 12
Harrison/1998 32 76 56 42 59
Madariaga/1998 34 67 40 35 19
Roayaie/1998 16 86 64 21 43
Weimann/ 2000 95 64 31 21 18
Weber/ 2001 33 83 55 31 37
Lang/ 2005 27 65/88* 53/77% 46*
* R0 only
Lang et al.,
Ann Surg 2005, 241-
Weimann et al,
Br J Surg 2000
Treatment options
LTx alone
LTx plus Whipple
LTx plus cluster resection-transplantation
n = 12
3-months mortality 2/12 (17%)
Survival: 3 pts. alive at time of report
52, 54, 59 months
Alessiani et al., J Am Coll Surg 1995
ICC n=6
Klatskin n=9
CCC in PSC n=4
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
Cholangiocarcinoma
University of Essen: 1987-2006
Liver Transplantation n = 19
Overall survival
1,0 1,0
0,9 0,9
0,8 0,8
0,7 0,7
Surviving
Surviving
0,6 0,6
0,5 0,5
0,4 0,4
0,3 0,3
0,2 0,2
0,1 0,1
0,0 0,0
0 12 24 36 48 60 72 84 96 108 120 0 12 24 36 48 60 72 84 96 108 120
Time (months) Time without hospital mortality (months)
after 01.04.1998
before 01.04.1998
1,0 1,0
0,9 0,9
0,8 0,8
0,7 0,7
Surviving
Surviving
0,6 0,6
0,5 0,5
0,4 0,4
0,3 0,3
0,2 0,2
0,1 0,1
0,0 0,0
0 12 24 36 48 60 72 84 96 108 120 0 12 24 36 48 60 72 84 96 108 120
tumor free time (months) tumor free time without hospital mortality [months]
1,0 1,0
0,9 0,9
0,8 0,8
Surviving
Surviving
0,7 0,7
0,6 0,6
0,5 0,5
0,4 0,4
0,3 0,3
0,2 0,2
0,1 0,1
0,0 0,0
0 12 24 36 48 60 72 84 96 108 120 0 12 24 36 48 60 72 84 96 108 120
Time (months) Time without hospital mortality (months
p=0,234 p=0,357
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
Cholangiocarcinoma
Early diagnosis: Tumor Markers
Other Markers:
ERBB-2, COX-2
Endo K et al, Hepatology 2002
K-ras Kubicka S et al, Gut 2005
INK4a/ADP ARF…..?? Klump B et al, Clin Cancer Res 2003
(HCC)
Hepatoblastoma
CCC
neuroendocrine (NE)
Metastatic tumors
non NE Colorectal
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
Epitheliod Hemangioendothelioma
Transplantation
Intermediate malignancy
Survival 2y 5y
80% 40%
Hemangioendothelioma AW 63 mo
( Hemangioendothelioma ) -> Stroma T. G1* AW 6 mo
Liver Stroma Tumor (angiosarcoma)* DWD 9 mo
Gastrointestinal Stromal
Tumors
GIST
Prognostc parameters
-C-KIT mutations
One patient
-12 years tumor history
- 6 years after LDLT
David B. Skinner MD
The Phemister Dallas Professor of Surgery
*
*
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen
LTx for
irresectable neuroendocrine (NE) liver
metastases
Indication :
Symptomatic Metastases
(neuroendrocrinological symptoms, pain, liver failure)
146 Pts.
34Pts.
evaluated
for OLT
Octreoscan
68Ga-DOTATOC-PET / CT
Liver biopsy
- Ki67 > 10% negative predictor of
survival
Exploratory laparotomy
Pretransplant Evaluation
- Results -
32 Pts.
Excluded Listed
11 21
10 extrahep.
1 died
tumor
1 waiting list
1 carcinoid heart
Results
19 Patients transplanted
7 LDLT
1 Cluster TX
Chemotherapy
1 M 67 Bronchus Carcinoid syndrome Lung lobectomy
Octreotide
Chemotherapy
2 M 52 Bronchus Carcinoid syndrome Lung lobectomy
Octreotide
Adominal
3 F 59 Pancreas Distal pancreatectomy Octreotide
discomfort
Carcinoid syndrom
Upper abdominal Chemotherapy
4 M 37 Pancreas Abdominal
exenteration Octreotide
discomfort
5 F 44 Pancreas Diarrhoe Pancreatoduodenectomy Octreotide
Carcinoid syndrome Left hepatectomy
6 M 52 Colon Abdominal Right hemicolectomy Octreotide
discomfort Chemotherapy
Liver failure
7 M 46 Pancreas Abdominal Whipple- Procedure Chemotherapy
discomfort
Number of
patients
No complications 9
Re-transplantation 1
Morbidity
THA 1
Lymph fistula 1
Bile leakage 2
Mortality
Cardiac reasons 2
Sepsis, rejection 1
Sepsis 2
Tumor recurrence 1
Tumor-free survival
Tumor recurrence
- Invasive treatment -
Conclusion
Radionuclide treatment
General Survey
Indications - Results
Organ allocation
Immunosuppression
Organ allocation
Vs
Donor risks!!
Recipients: suboptimal results in
- advanced tumors
- severe cirrhosis
Liver Transpl. 2001 7:9217
General Survey
Indications
Organ allocation
Immunosuppression
New Molecules
Immunosuppressive Strategies
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Wyeth Sirolimus
Thymoglobulin
Genzyme
Alemtuzumab
BMS Belatacept*
Individualized immunosuppression
Individualized immunosuppression
SILVER
A PROSPECTIVE RANDOMIZED, OPEN-LABELED TRIAL
COMPARING
SIROLIMUS-CONTAINING
VERSUS
mTOR-INHIBITOR-FREE IMMUNOSUPPRESSION