Functional assessment of the rapidly growing liver

Transcription

1 Functional assessment of the rapidly growing liver Erik Schadde Assistant Professor of Surgery Dept. of Surgery Liver Transplanation and Liver Surgery Rush University Medical Center Chicago Illinois Cantonal Hospital Winterthur and University of Zürich Zürich- Switzerland 5 th International Workshop on the Treatment of Hepatic and Lung Metastases of Colorectal Carcinoma BARCELONA, SPAIN Nov 12 th 2015

2 Topics 1. Rapid hypertrophy of the liver 2. Outcome after resection and liver volume 3. Causes of mortality in rapid hypertrophy 4. HIDA scan for liver function

3 27 healthy living donors after donor hepatectomy remnant: 60% 88% increase mean in 10 days Kinetic growth: 9% per day Hypertrophy after partial hepatectomy Nadalin/ Malago/ Broelsch Liver Transpl 2012

4 Portal vein embolization - hypertrophy 44 studies on portal vein embolization 38 (range ) % increase in 26 (range 14-42) days Kinetic growth 1.4 % per day Van Lienden/van Gulik Cardiovasc Intervent Radiol 2013

5 ALPPS hypertrophy 25 patients in the inaugural German report 78% increase (mean) in 9 days (mean) Kinetic growth 8.7% per day (mean) Schnitzbauer/Lang/Schlitt Ann Surg 2012

6 ALPPS hypertrophy 62 patients in the French-Belgian cooperative study 49% increase (mean) In 11 days (mean) Kinetic growth 6.6% per day (mean) Truant/Scatton/Regimbeau/Lucidi/Donkier/Soubrane/Adam/Pruvot EJSO 2015

7 Rapid vs. slow hypertrophy comparative study 48 patients with ALPPS 77.4% increase in 7.8 days Kinetic growth 9.9 % per day 86 patients With PVE/PVL 34.1% increase in 50 days Kinetic growth 0.6 % per day Schadde/Clavien World J Surg 2014

8 Mortality ALPPS vs.tsh TSH ALPPS Mortality of ALPPS is likely higher than conventional TSH Rate of liver failure (ISGLS): 30% Rate of liver failure (50-50): 9% ( 320 patients/73 centers Schadde/Clavien Ann Surg 2015)

9 Topics 1. Rapid hypertrophy of the liver 2. Outcome after resection and liver volume 3. Causes of mortality in rapid hypertrophy 4. HIDA scan for liver function

10 Extent of resection is a strong predictor of mortality Jarnagin/Blumgart, Ann Surg 236, 4, 2002

11 Complexity Jarnagin/Blumgart, Ann Surg 236, 4, 2002

12 Complexity <-> remnant volume Extent of resection beats complexity any time Jarnagin/Blumgart, Ann Surg 236, 4, 2002

13 The primacy of liver remnant volume Liver remnant volume Bile leak Anastomotic leaks Deep infections Superficial infections Wound healing Malnutrition

14 ALPPS patients get resected at higher liver volumes % 86 patients undergoing two-stage hepatectomies with PVE/PVL p=0.007 Stage 2 48 patients undergoing ALPPS p=0.06 Stage 1 PVE/PVL ALPPS patients undergo ALPPS resection at higher liver volumes than patients with two-stage hepatectomies Schadde/Clavien World J Surg 2014

15 Mortality of ALPPS TSH ALPPS The higher mortality of ALPPS is not explained by lower remnant volumes.

16 Topics 1. Rapid hypertrophy of the liver 2. Outcome after resection and liver volume 3. Causes of mortality in rapid hypertrophy 4. HIDA scan for liver function

17 Causes of mortality in ALPPS 1 st registry report: 202 patients 19 mortalities 2 nd registry report: 320 patients 28 mortalities Schadde/Clavien Ann Surg 2015

18 Study design Schadde/Clavien Ann Surg 2015

19 What we call cause of death 71 year old man with large HCC sflr 22% Stage 1 ALPPS Day 0 Stage 2 ALPPS Day 7 Death Day 36 Day 2 mild delirium Day 7 Day 8 Day 12 sflr week 31% Rising bilirubin Bili 140 mmol/l INR 1.6 Crea rising ROOT cause: Patient selection: Age? Tumor type? Liver function assessment? DOMINANT complication: Deterioration of liver function test LIVER Failure Criteria Yes Day 34 Septic shock DIRECT cause of death: Septic shock Schadde/Clavien Ann Surg 2015

20 Causes of 28 mortalities after ALPPS Dominant complication Liver failure by any criterion yes/no Direct cause of death Most mortalities in ALPPS are due to Post-hepatectomy liver failure Schadde/Clavien Ann Surg 2015

21 140 step1 Synthetic function step2 First 13 ALPPS patients Zurich 2012 Prothrobin time (%) month 3 months Key role of the auxiliary liver

22 Synthetic function in ALPPS patients Synthetic function declines after ALPPS stage 1 without any mass reduction but recovers rapidly Alvarez/Sanitbanes Ann Surg 2015

23 Liver failure criteria after surgery are largely based on INR and bilirubin levels 50/50 criteria Day 5 postop Bili > 50 µmol/l (2.9 mg/ml) AND Quick value <50% (INR 1.7) Balzan/Belghiti Ann Surg 2005 Bili > 7 criteria Peak Bili post-op Bili > 7mg/dl (120 µmol/l) Mullen/Vauthey J Am Coll Surg 2007 ISGLS criteria Day 5 postop Abnormal Bili AND INR Rahbari/Büchler Surgery 2011 Schadde/Clavien Ann Surg 2015

24 Liver function assessment after ALPPS by liver failure criteria Stage 1 ALPPS Stage 2 ALPPS Liver failure after stage 1 is rare, but 14 % of patients fulfill ISGLS criteria after stage 1 Schadde/Clavien Ann Surg 2015

25 Liver failure after stage 1 and mortality Delay stage 2 ALPPS in patients with abnormal liver function tests after stage 1 Schadde/Clavien Ann Surg 2015

26 Liver volume prior to stage 2 ALPPS does not predict mortality Schadde/Clavien Ann Surg 2015

27 Topics 1. Rapid hypertrophy of the liver 2. Outcomes after resection and liver volume 3. Causes of mortality in rapid hypertrophy 4. HIDA scan for liver function

28 Imagine a unilateral nephrectomy in : Kocher performs an anterior transperitoneal nephrectomy through a midline incision. 1885

29 Laboratory liver function tests to assess outcome before resection

30 HIDA =Hydroxyiminoacetic acid ALBUMIN HIDA HIDA Hoekstra/van Gulik Ann Surg 2013

31 Regional uptake of liver (avidity) and liver remnant in planar scintigraphy Hoekstra/van Gulik Ann Surg 2013

32 Remnant function of patients with post hepatectomy liver failure in Amsterdam De Graaf/ Van Gulik J Gastrointest Surg 2010

33 Establishment of a liver clearance value predicting liver failure using a ROC curvethe Amsterdam index 55 patients prior to liver resection, 30 with diseased parenchyma MINIMUM FLR Clearance prior to resection: 2.7 %/min/m 2 The established and validated uptake cut-off to prevent liver failure is 2.7 %/min/m 2 De Graaf/ Van Gulik J Gastrointest Surg 2010

34 Uptake function in an ALPPS patient Window of interest: sec

35 Determination of FLR function in an ALPPS patient HIDA and uptake function can be used in ALPPS Prior to stage 1 1 week after later, prior to stage 2

36 FLR clearance and volume in an ALPPS patient with a good outcome Volume prior to stage 1 Function prior to stage 1 Volume prior to stage 2 (day 7) FLR 278 cc 2.0%/min/m cc (x 2.0) Function prior to stage 2 (day7) 5.4%/min/BSA (x 2.7) Deportalized 925 cc 4.6%/min/m cc 3.7%/min/BSA lobe Prothrombin NADIR on (x POD 0.86) 2: 87% (x 0.80) Total liver 1203 cc 6.6 %/min/m cc (x 1.12) 8.1%/min/BSA (x 1.23)

37 FLR clearance and volume in an ALPPS patient with a bad outcome FLR Deportalized lobe Prothrombin NADIR on POD 2: 60%! Bili peak 47 mmol/l on POD 5! volume prior to stage 1 function prior to stage 1 volume day cc 0.88%/min/m 2 407cc sflr 0.10 sflr 0.24 (x 2.36) 1350 cc 4.32 %/min/m cc (x 0.94) Total liver 1522cc 5.20 %/min/m cc function day7 0.65%/min/BSA!!! (x 0.73) 3.7%/min/BSA (x 0.29) 1.96%/min/BSA If global function decreases after stage 1, (x 1.12) (x 0.37) it is always failure of the auxiliary liver

38 FLR clearance and volume in an ALPPS patient with a bad outcome FLR Deportalized lobe Total liver volume day week cc sflr 0.29 (x 2.98) 1120 cc (x 0.82) function week %/min/m 2 (x 2.27) 2.76 %/min/m 2 (x 0.63) volume week cc sflr 0.31 (x 3.15 ) 1085cc (x 0.80) function week %/min/BSA!! (x 2.95) 1.05 %/min/m 2 (x 0.24) The growing FLR may compensate for the lack 1633 cc 4.76 %/min/m cc of function of the DPL over time, 3.65%/min/m 2 (x1.07) but it (x0.91) is David against (x 1.06 Goliath ) (x 0.69)!

39 FLR clearance and volume in an ALPPS patient with a bad outcome FLR Deportalized lobe Total liver volume day cc sflr 0.29 (x 3.01) 980 cc (x 0.72) 1493 cc function day 28 Amsterdam index 2.84%/min/m 2! (x 3.23) 2.56 %/min/m 2! (x 0.59 ) 5.4 %/min/m 2 Stage 2 resection Asymptomatic bile leak antibiotics Fungal sepsis Death day 42 (x 1.26) (x 1.04) Diagnosis: right lobe failure and volume-function dissociation of the left lobe

40 Right and left lobe liver failure in ALPPS Etiology: Deep surgical space infections Bile leaks Underrescuscitation and use of pressors Syndrome of the inter- stage failure of the auxiliary ( right ) lobe Syndrome of Inter-stage inadequate function gain gain despite adequate volume gain

41 RELATIVE HIDA UPTAKE OF THE FLR (%/min/m2) Not enough volume or function Prior to stage 1 06/19/ weeks after stage 1 07/06/ week after stage 1 06/29/ weeks after stage 1 07/17/ weeks after stage 1 07/17/2015 Enough volume or function AVOID stage 2 when volume increases 0 0,00 without 0,10 0,20 functional 0,30 increase 0,40 0,50 0,60 STANDARDIZED FUTURE LIVER VOLUME (sflr)

42 What happened to these patients in the past in two-stage hepatectomies? STAGE 1 Portal vein manipulation Failure to grow 25% 75% Tumor progression STAGE 2 Completion hepatectomy second stage 75% feasibility

43 RELATIVE HIDA UPTAKE OF THE FLR (%/min/m2) Not enough volume or function Prior 2 weeks 1 week 3 weeks 4 weeks Enough volume or function FLR 0 0,00 AVOID 0,10 to go 0,20 into the 0,30second 0,40 stage 0,50 with 0,60 STANDARDIZED FUTURE LIVER VOLUME (sflr) marginal FLR function 4 weeks 3 weeks DPL 2 weeks 1 week

44 Risk factor for mortality: MELD prior to stage 2 Avoid to perform stage 2 ALPPS if MELD is 10 Schadde/Clavien Ann Surg 2015

45 in-situ split hepatectomy Liver function Bile leak Deep infections Superficial infections Recovering from major surgery Wound healing Malnutrition

46 The safest way to avoid complications in ALPPS RELATIVE HIDA UPTAKE OF THE FLR (%/min/m2) Not enough volume or function Enough volume or function 2 Extremly 1 Small abnormal parechyma FLRs 0 0,00 0,10 0,20 0,30 0,40 0,50 0,60 STANDARDIZED FUTURE LIVER VOLUME (sflr)

47 Conclusions 1. Rapid hypertrophy is a reality. 2. ALPPS likely has a higher mortality than conventional methods of inducing hypertrophy 3. Remnant liver function was the primary determinant of outcome after liver resection in the past 4. Volume and function are dissociated in rapid hypertrophy ALPPS induces hypertrophy despite complications, bile leaks, infections etc. 5. Functional assessment of the rapidly growing liver is indispensable when dealing with rapid hypertrophy 6. In PSEUDOALPPS a two-stage hepatectectomy is performed in patients who may well be resected in one stage,

48 50% 50% Thanks to Pierre-Alain Clavien (CH) Beatrice Beck-Schimmer (CH) Eduardo de Santibanes (AR) Victoria Ardiles (AR) Allessandro Serrablo (S) Andreas Schnitzbauer (G) Massimo Malago (UK) Ricardo Robles Campos (E) Olivier Soubrane (F) Marcel Machado (BR) Stefan Breitenstein (CH) Martin Hertl (USA) Fellows and residents: Greg Sergeant (Hasselt-B) Georg Lurje ( Aachen-G) Chris Soll (Winterthur-CH) Xavier Keutgen (DC -USA) Dimitri Raptis (Olten -CH) Chistopher Tsatsaris (Zürich-CH) Becca Deal (Chicago USA) Charlie Fredericks (Chicago-USA)