portal embolization increasing liver volume and function€¦ · · 2015-12-10– the future...

5th International Workshop on the Treatment of Hepatic and Lung Metastases of Colorectal Carcinoma

Barcelona. November 2015

Colorectal Liver Metastases Barcelona. 2015

Portal Embolization Increasing Liver Volume and

Function

Juan Carlos García-Valdecasas Salgado Jefe de Servicio de Cirugía

Catedrático de Cirugía Hospital Clínic. Universidad de Barcelona




• MULTIPLES ESCENARIOS – Según la Magnitud: – Tamaño, Número, Localización, – Indice de Afectación Hepática – Según el Tiempo de Aparición: – Sincrónicas y Metacrónicas – Según Respuesta al Tratamiento QT

– POSIBILIDAD DE RESECCION

Enfermedad metastásica CCR



Colorectal Liver Metastases Barcelona. 2015 Definition of Resectability….

• In the context of the metastatic disease – Loco/Regional Recurrence – Concomitant Metastases

• Any Patient – In whom all disease can be remove with a

negative margin* – Who has an adequate remnant hepatic

volume/reserve * De Haas RJ et al Ann Surg 248:626-637, 2008




• Increased Safety • Increased knowledge

– Understanding Segmental Anatomy • Vascular and biliary tract distribution

– Understanding Postoperative Immediate Function • Acute Liver Failure

Limits of Resectability….

• Importance of – The Future Liver Remnant Volume



Colorectal Liver Metastases Barcelona. 2015 Strategies to Liver Resection….

• Strategies to downsize metastatic disease 1. Neoadjuvant Chemotherapy

• Strategies to increase FLR volume 1. Interventional Radiology

• Portal Vein Embolization

2. Surgical Approach a. Two Stage Hepatectomy b. Two-stage Partition and Hepatectomy (ALPPS) c. Vascular Resection and Reconstruction d. “In situ” Hypothermic Liver Perfusion



Colorectal Liver Metastases Barcelona. 2015 CASO CLINICO (1)




• The role of new Chemotherapy Agents CASO CLINICO (2)




•2009 (Junio-Noviembre)

•QT neoadyuvante. FOLFOX + RAMUCIRUMAB x7 de •2009 (Octubre)

•TC TORACOABDOMINAL. Disminución significativa •TLV: 1.536 ml. FLR: 387 ml.(25%)

•2009 (Diciembre) •Intervención Qurúrgica: Hemicolectomia derecha y Hepatectomia derecha+Res.Seg.Les. SIII

Enfermedad actual




Curso Postoperatorio

•Día +5. Insuficiencia Hepática Posthepatectomía

•Bil. 5.4 mg/dL. TºP. 47%. Ascitis.

•Día +15. Alta Hospitalaria

•AP. Higado no tumoral afectado por QT • Síndrome de Obstrucción Sinusoidal




•2010 (Agosto).

•TAC/PET. Recidiva Unica Hepática y ganglionar •FOLFIRI+Bevacizumab x16

•2010 (Diciembre) •FGS. Varices esofágicas grado I. Ulcera Péptica

•2011 (Mayo). •Plaquetopenia y Esplenomegalia

•2011(Noviembre). •Varices esofágicas (grado II). Circulación Perigástrica •HDA por varices esofágogástricas. Banding x4 •Elastografía Hepática. 10.0 kPa

Evolución




Evolución •2012 (Octubre). Varices esofágicas grado III •2013 (Diciembre). Encefalopatía Hepática

•Bil 4 mg/dL, Plaquetas 34000 y TP 48%. •2014 (Marzo). QT de mantenimiento (se para)

•Capecitabina + Bevacizumab

•2014 (Septiembre): Nuevo episodio de Encefalopatia •2015 (Febrero). Exitus



Colorectal Liver Metastases Barcelona. 2015 Strategies to Liver Resection….

• Strategies to downsize metastatic disease 1. Neoadjuvant Chemotherapy

• Strategies to increase FLR volume 1. Interventional Radiology

• Portal Vein Embolization

2. Surgical Approach a. Two Stage Hepatectomy b. Two-stage Partition and Hepatectomy (ALPPS) c. Vascular Resection and Reconstruction d. “In situ” Hypothermic Liver Perfusion




• Objective – Increase FLR Volume and Function

• In order to Avoid PHLF – Incidence: Low. 10%-20%. Associated 65% mortality – Depends on Remnant Liver

– Volume. » FLR/ sFLR Ratio > 20%

– Function. Affected by » Age » Chemotherapy » Fibrosis » Infection

Portal Vein Embolization…




• Evaluating Liver Volume • Measured Total Liver Volume

– Calculated Liver Volumetry (CT o MR) • Estimated Liver Volume

– Based on Relation between Liver Size and BSA – Based on Relation between Liver Size and Body weight

(LR/BW ratio)

• Future Liver Remnant (FLR) – Expressed as a ratio of the Total Liver Volume

Avoiding PHLF…

Ribero D et al. Ann Surg 258:801-807, 2013



Colorectal Liver Metastases Barcelona. 2015 Portal Vein Embolization…




• Importance of Preoperative Liver Volumetry

Portal Vein Emnbolization…

FLR and… A. PHLF B. PHLF and Death




• Importance of a Healthy Liver


• Chemotherapy. Side effects. • Oxaliplatin-based

– Sinusoidal Dilatation – Vascular Congestion – Presinusoidal fibrosis – Venous occlusion

• Irinotecan based – Steatohepatitis

Vauthey JN et al. J Clin Ocol 2006:24;2065 Reddy SK et al. J Am Col Surg 2008:206;96 Karoui M et al. Ann Surg 2006:243;1-7




….and does not increase overall survival or disease free survival

Scoggins CR et al. Ann Surg Oncol 2009:16;35-41

Preoperative Chemotherapy and Short and Long Term Outcome


A sFLR >30% should be considered




Current Criteria Increasing FLR volume

Liver Pathology • Indication for PVE Normal Injured

• FLR/TLV <25% <30% • FLR/BWR <0.5% <0,8%


Scoggins CR et al. Ann Surg Oncol 2009:16;35-41 Shindoh J et al J Am Col Surg 2013:126-134





• Portal Vein Embolization • Method

• Great Variability 1. Percutaneous Approach Polivynil Alcohol Trysacryl Microsphere Coils 2. Technique Right Portal Vein (rPVE) rPVE+sIV



Colorectal Liver Metastases Barcelona. 2015 Embolización portal



Colorectal Liver Metastases Barcelona. 2015 Embolización Portal Selectiva



Colorectal Liver Metastases Barcelona. 2015 Imagenes Post embolización Portal




Volumen preembolización 371,08 cc

Volumen postembolización 559,35 cc



Colorectal Liver Metastases Barcelona. 2015 243,88 ml 387 ml

Incremento del 58,7%




Shindoh J et al J Am Col Surg 2013:126-134

Study Population




Long Term Outcome after rPVE+sIV






•Important Messages

•Mortality 5,8% •Morbidity 32,7%

1. Indicated in patients under the age of 60 2. Feasibility of 72% (vs. 95%) 3. Abscence of Stage 1 Morbidity 4. Significant waiting Period. >4 weeks Oncologic Selection (drop out) ALPPS associated to a 20% recurrence at 3 months





Truant S et al ….and on behalf of the e-HPBchir Study Group from the Association de Chirurgie Hepato-Biliaire et de Transplantation (ACHBT)

EJSO 41 (2015) 674e682

Indication for ALPPS Normal Injured RLV/TLV <25% <30% RL/BWR <0.5% >0,8% As an alternative to 2 stage 34 (54,8%) As the only Surgical Option 28 (45,2%) After Failed PVE 9 (14,5%) Intraoperative Decission 7 (11,3%)

ALPPS Volume Increase in between Relative gain 48,6% RLV/TLV 39,1% Gain in RL/BWR 0,25%




Truant S et al EJSO 2015, 41:674-682





•Important Messages

•Mortality 12,9% •Morbidity 40,3%

1. Indicated in patients under the age of 60 2. Feasibility of 95,2% (vs. 66-75%) 3. Stage 1 major morbidity Is a prognostic factor of cumulative mortality 5/14 (35,7%) vs 3/48 (6,3%) 4. Waiting beyond 7 days seems to be useless KGR 33,3 ml/day vs 17,2 ml/day 5. Systematic use of PVE before ALPPS ?

Truant S et al EJSO 2015, 41:674-682





Failure to achieve a two-stage hepatectomy:

what predictive factors and what practical consequences?

Katsunori Imai1,2,5, Carlos Castro Benitez1,2,4, Marc-Antoine Allard1,2.4, Eric Vibert, 1,3,4, Antonio Sa Cunha1,4, Daniel Cherqui1,4, Denis Castaing1,3,4,

Henri Bismuth, Hideo Baba5, René Adam1,2,4 1Centre Hépato-Biliaire, AP-HP, Hôpital Paul Brousse, Villejuif, France 2Inserm, Unité 776, Villejuif, France 3Inserm Unité 785, Villejuif, France 4Université Paris-Sud, Villejuif, France, Villejuif, France 5Department of Gastroenterological Surgery, Kumamoto University, Japan

Courtesy of Rene Adam




Between January 2000 and December 2012, 845 patients underwent hepatectomy for colorectal liver metastases at Paul Brousse Hospital.

Among these, 125 patients (14.8%) with initially unresectable multiple and bilobar CRLM were scheduled to perform TSH and were enrolled in this study.

Study population




AIM 1. Identify the independent factors to predict the

failure to achieve two-stage hepatectomy by multivariate logistic analysis.

2. Based on the multivariate logistic model, the predictive model for failure of two-stage hepatectomy was developed.

3. Optimal cut-off values for continuous data were determined by receiver operating characteristic (ROC) curve analysis.




median range Age 56.1±9.7 57 31-82 Gender 68/57 Body mass index 24.9±4.5 24 17-40 ASA score (I/II/III) 10/95/20 Timing of liver metastasis (synchronous†/metachronous) 112/13 Site of primary tumor (colon/rectum) 93/32 Primary T stage (1-2/3-4) 17/94 Primary N stage (0/1-2) 27/85 CEA at diagnosis (ng/dL) 1187.2±5696.3 83 0.4-48332 CEA at hepatectomy (ng/dL) 65.0±283.4 8 0.4-2960 Tumor number at diagnosis 10.6±6.9 9 2-35 Tumor number at hepatectomy 10.2±6.1 9 2-33 Largest tumor size at diagnosis (mm) 51.2±31.7 45 10-164 Largest tumor size at hepatectomy (mm) 42.4±24.1 37 12-150 Percentage of FLR volume (%) 29.3±7.9 30 15-53 ICG-R15 value (%) 9.6±6.0 8.4 2-33.6 Concomitant extrahepatic disease 34 (27.2%)

Lung 22 Lymph node 7 Peritoneum 5

Background characteristics




median range

Chemotherapy before 1st-stage hepatectomy 123 (98.4%)

Chemotherapy cycles 12.3±7.3 11 1-34

Chemotherapy lines 1 1-4

1 83

2 26

≥ 3 14

Chemotherapy regimen

1st line (oxaliplatin/irinotecan/both/other) 79/46/4/4

2nd line (oxaliplatin/irinotecan/both/other) 12/22/4/3

3rd line (oxaliplatin/irinotecan/both/other) 1/6/2/2

Use of biologic agents 82 (66.7%)

Tumor progression during 1st-line chemotherapy 14 (11.5%)

Chemotherapy features




median range Interval chemotherapy 60 (74.1%) Time interval between 1st- and 2nd-stage (month) 4.0±3.0 3.2 1.1-15.7 Major hepatectomy 75 (92.6%) Type of procedure

anatomical 64 anatomical + limited 16 limited 1

Concomitant use of local ablation therapy 5 (6.2%) radiofrequency ablation 5 cryotherapy 0

Vascular clamping 69 (85.2%) Clamping time 41.6±18.0 43 12-85 Blood loss (g) 1320.9±1375.2 1000 170-6900 Operating time (min) 399.8±104.8 391 190-894 Blood transfusion 41 (50.6%) Number of resected nodule* 7.4±5.4 7 0-26 Resection margin status (R0/R1/Rx**) 35/44/5 In-hospital stay 11.5±6.3 10.5 3-76

Operative features (2nd-stage, n=81)

*including the nodule treated with local ablation therapy **treated with local ablation therapy




1st-stage (n=125) Major complication (Clavian-Dindo ≥ III) 18 (14.4%)

III/IV/V 14/4/1* fluid collection 7 bile leakage 2 transient liver failure 2 intraabdominal bleeding 1 transient renal failure 1 intraabdominal abscess 1 anastomotic leakage 1 urinary tract obstruction due to infection 1 sepsis 1 acute coronary syndrome 1

90-day mortality 1 (0.8%) 2nd-stage (n=81)

Major complication (Clavian-Dindo ≥ III) 27 (33.3%) III/IV/V 18/9/2** bile leakage 10 fluid collection 5 transient liver failure 6 intraabdominal bleeding 2 catheter infection 1 abdominal wall abscess 1 sepsis 1 transient renal failure 1 fetal liver failure 2

90-day mortality 2 (1.6%)

Complication




median range

Total number of removed tumor* 9.0±7.4 7 0-32

Size of largest tumor removed 35.9±23.7 30 0-130

Resection margin status (R0/R1 or Rx**/R2) 13/68/44

90-day mortality 3 (2.4%)

Total results of two-stage hepatectomy (n=125)

*including the nodule treated with local ablation therapy **treated with local ablation therapy




100

0

80

60

40

20

0 1 2 3 5 4 6 7 8 9

Overall survival stratified on the basis of whether completed (n=81) or failed (n=44)

Years after first-stage hepatectomy

Ove

rall

surv

ival

0 1 2 3 4 5 6 7 8 9

81 72 55 34 22 14 7 5 3 2

44 23 7 3 - - - - - -

Patients at risk

P<0.0001

44.2% Two-stage hepatectomy

completed (n=81)

Two-stage hepatectomy not completed (n=44)

Completed

Not completed




Completed (n=81) Failed (n=44) P Age > 50 58 (71.6%) 36 (81.8%) 0.20 Gender (male/female) 43/38 25/19 0.69 Body mass index > 24 39 (48.2%) 27 (61.4%) 0.16 ASA (I/II/III) 9/58/14 1/37/6 0.12 Timing of liver metastases (synchronous†/metachronous) 75/6 37/7 0.15 Site of primary tumor (colon/rectum) 59/22 34/10 0.59 Primary T stage (1-2/3-4) 9/65 8/29 0.20 Primary N stage (0/1-2) 20/55 7/30 0.36 CEA at diagnosis > 30 (ng/dL) 51 (65.4%) 29 (78.4%) 0.15 CEA at hepatectomy > 30 (ng/dL) 13 (16.1%) 18 (42.9%) 0.0014 Tumor number at diagnosis > 9 42 (51.9%) 17 (38.6%) 0.16 Tumor number at hepatectomy > 9 41 (50.6%) 17 (38.6%) 0.20 Tumor size at diagnosis > 40 (mm) 42 (51.9%) 28 (63.6%) 0.20 Tumor size at hepatectomy > 40 (mm) 24 (30.0%) 27 (61.4%) 0.0006 Chemotherapy before 1st-stage hepatectomy 79 (97.5) 44 (100%) 0.19 Chemotherapy cycles before hepatectomy > 12 17 (21.5%) 27 (61.4%) <0.0001 Chemotherapy lines before chemotherapy > 1 18 (22.8%) 21 (47.7%) 0.0048 Use of biologic agents 53 (67.1%) 29 (65.9%) 0.89 Tumor progression during 1st-line chemotherapy 3 (3.6%) 11 (25.0%) <0.0001 Percentage of FLR volume > 30 (%) 20 (44.4%) 7 (41.2%) 0.82 ICG-R15 > 10 (%) 29 (37.7%) 19 (47.5%) 0.31 Concomitant extrahepatic diseases 20 (24.7%) 13 (29.6%) 0.56 Major hepatectomy at 1st-stage 1 (1.2%) 1 (2.3%) 0.67 Vascular clamping at 1st-stage 43 (53.1%) 21 (47.7%) 0.57 Concomitant use of local ablation therapy at 1st-stage 6 (7.4%) 6 (13.6%) 0.27 Blood loss > 200 g at 1st-stage 38 (46.9%) 16 (36.4%) 0.25 Operating time > 386 min at 1st-stage 22 (27.2%) 19 (43.2%) 0.071 Blood transfusion at 1st-stage 41 (50.6%) 23 (52.3%) 0.86 Number of removed tumor ≥ 3 at 1st-stage 56 (69.1%) 26 (59.1%) 0.26

Comparison of the patients who completed or failed to achieve two-stage hepatectomy




RR 95%CI P

CEA at hepatectomy > 30 (ng/dL) 2.73 1.08-7.05 0.034

Tumor size at hepatectomy > 40 (mm) 2.89 1.07-7.97 0.036

Chemotherapy cycles before hepatectomy > 12 3.46 1.35-9.05 0.0098

Tumor progression during 1st-line chemotherapy 6.56 1.53-35.63 0.01

Multivariate logistic regression analysis of predictive factors for failure of two-stage

hepatectomy

*Cut-off values were determined by ROC analysis




Factors CEA at hepatectomy > 30 (ng/dL)

Tumor size at hepatectomy

> 40 (mm)

Chemotherapy cycles before hepatectomy

> 12

Tumor progression during 1st-line chemotherapy

Probability (%)

0 − − − − 10.5 1 + − − − 25.3

− + − − 24.3 − − + − 28.9

− − − + 43.5 2 + + − − 48.1

+ − + − 54.0 + − − + 69.0 − + + − 52.6

− + − + 67.8 − − + + 72.7 3 + + + − 76.2 − + + + 87.9 + − + + 88.5 − + + + 87.9 4 + + + + 95.5

Predictive model for failure of two-stage hepatectomy based on multivariate logistic model



Colorectal Liver Metastases Barcelona. 2015 Receiver operating characteristic (ROC) curve of the proposed predictive model

Sens

itivi

ty

1-specificity

1.0

0

0.8

0.2

0.6

0.4

1.0 0 0.8 0.2 0.6 0.4

The c-index: 0.81





Ove

rall

surv

ival


0

100

20

80

60

40

Ove

rall

surv

ival

0 1 9 2 3 4 5 6 7 8

0 1 2 3 4 5 6 7 8 9

44 36 27 17 11 8 2 2 1 1

31 27 19 8 5 2 2 - - -

30 21 12 8 5 3 3 3 2 1

11 5 2 1 - - - - - -

4 2 - - - - - - - -

Patients at risk

0

100

20

80

60

40

0 1 9 2 3 4 5 6 7 8

0 1 2 3 4 5 6 7 8 9

105 84 58 33 21 13 7 5 3 2

15 7 2 1 - - - - - -

Patients at risk Score

0-2

3-4

P<0.0001

0

1 2 3

0-2

3-4

Overall survival according to the predictive score

score

0

1

2

3

4

4

Score 0-2 vs. 3-4




Proposed predictive model by CEA, tumor size, preoperative chemotherapy cycles, and response to chemotherapy contribute to the selection of appropriate patients who expected to benefit from the strategy of two-stage hepatectomy

Patients with ≥ 3 factors should be contraindicated because of their higher failure rate.

Avoidance of these risk factors significantly reduces the risk of drop-out and is crucial for the long-term survival.

Conclusions



Colorectal Liver Metastases Barcelona. 2015 Resumen

• La Embolización de la Vena Porta – Capaz de mejorar el índice de resecabilidad aumentando el tamaño

de Volumen Hepático Residual (72%). – La capacidad de estimulación está condicionada por la Edad,

Fibrosis, Quimioterapia, Infección… – Se asocia a una Morbididad (33%)y Mortalidad (5%) razonable – La presencia de CEA elevado, Tamaño tumoral por encima de 4

cm, Ausencia de Respuesta a la QT, y el empleo de mas de 12 ciclos, son factores de mal pronóstico

– Es necesario un seguimiento a largo plazo para conocer las verdaderas consecuencias de tratamiento médico-quirúrgico.



Colorectal Liver Metastases Barcelona. 2015 Impact for expanding criteria for resectability…

Factores asociados •Edad superior a 70 años •Patología asociada •Quimioterapia Previa •Afectación hepática extensa •Tumores > 3 cm •Transfusión sanguinea* •Isquemia hepática alargada

Mortalidad: 0-6% Morbididad:22-45%

De Haas RJ et al Ann Surg 2011:253;1069




Laurent C et al Br J Surg 2003;90:1131

Impact for expanding criteria for resectability…

Supervivencia 3 años 5 años Global 53% 36% Sin Complicaciones 61% 43% ConComplicacines 21% 12% 0.001

Mortalidad: 3% Morbididad:30%




De Haas RJ et al Ann Surg 2011;253:1069

Impact for expanding criteria for resectability…

Supervivencia 3 años 5 años Sin Complicaciones 66% 52% Con Complicacines 60% 42% 0.001

Mortalidad: 1.3% Morbididad: 33%




• “A priori” –HEALTHY LIVER…

Definition of Resectability….




• Chemotherapy. Side effects. • Oxaliplatin-based

– Sinusoidal Dilatation – Vascular Congestion – Presinusoidal fibrosis – Venous occlusion

• Irinotecan based – Steatohepatitis


Vauthey JN et al. J Clin Ocol 2006:24;2065 Reddy SK et al. J Am Col Surg 2008:206;96 Karoui M et al. Ann Surg 2006:243;1-7



Colorectal Liver Metastases Barcelona. 2015 Chemotherapy Side effects. Postoperative Liver Faiulure




• Diagnóstico. Enfermedad Hepática Metástasica • Planteamiento quirúrgico. Hepatectomía

derecha reglada • Intervención. Hepatectomía

– Pérdidas de 375 ml. sin Exclusión Vascular – Protocolo: Somatostatina.

• Bolus. 250-500 µg en bolus • 250 µg/hora durante 7 dias

• Curso Postoperatorio – Insuficiencia hepática postoperatoria





• Curso Postoperatorio • Dias 1 a 3. Buen estado general • Dias 4 a 10. Deterioro Porogresivo

– Encefalopatía. – Alteración de la función.

• Bi. 10 mg y T.Protrombina. 20%

• Colocación del MARS – Cuatro sesiones

• A partir de entonces mejoría progresiva





Chemotherapy Side effects. Postoperative liver Faiulure



Colorectal Liver Metastases Barcelona. 2015 Estrategia Terapéutica….

• In the context of the metastatic disease – Loco/Regional Recurrence – Concomitant Metastases

• Any Patient – In whom all disease can be remove with a

negative margin* – Who has a remnant hepatic volume/reserve

* De Haas RJ et al Ann Surg 248:626-637, 2008

portal embolization increasing liver volume and function€¦ · · 2015-12-10– the future...

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