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SURGICAL THERAPY FOR INTRAHEPATIC PORTOSYSTEMIC SHUNTS
Dr David Cook BVSc MANZCVS (Small Animal Surgery) ANZCVS Surgery Chapter Resident’s Forum 2015
GENETIC COMPONENT OF IHPSS • Van Steenbeek Plos One 2013 • EHPSS have genetic changes suggesting microvascular underdevelopment, while IHPSS suggest defect of closure of ductus venosus • Increased levels of WEE1 expression may be protective against reduced O2 levels in ductus closure
DISTRIBUTION ! Weisse JAVMA 2014 –
! 100 cases
! 38 right division
! 33 Left divisional
! 19 central divisional
! Multiple shunts (10) ! 2 intrahepatic shunts (2) ! 1 intrahepatic and 1 extrahepatic (1) ! >2 intrahepatic shunts (7)
IMAGING OF PORTOSYSTEMIC SHUNTS ! Abdominal ultrasound – non invasive,
lacks planning capacity, operator dependent
! CT Angiography/venography – gold standard
! Kim VRU 2013 (EHPSS)
PSS
CVC
Coil
Stent
PSS
! MRI – requires specialised sequences and high power magnet ! Contrast portography – invasive, largely replaced by CT-A ! Nuclear Scintigraphy - poor anatomic localisation for surgical planning ! Retrograde balloon occlusion of azygous vein and CVC – replaced by CT-A
Other modalities
THERAPY FOR INTRAHEPATIC SHUNTS ! AIM = Improve perfusion and subsequent metabolism of GIT
derived toxic products and hepatic trophic factors
! Surgical management of single congenital portosystemic shunts improves life span and quality of life (Greenhalgh JAVMA 2010 + 2014) compared to medical management (89% medical died vs 22% surgical)
! MEDICAL MANAGEMENT
! TRADITIONAL SURGICAL APPROACHES • Extravascular, intravascular (rare) • Acute (partial) ligation vs gradual occlusion
! INTERVENTIONAL RADIOLOGY APPROACHES • Thrombogenic coil embolisation with or without vena cava
stenting (partial occlusion) • Amplatzer ductal occluder (acute occlusion)
MEDICAL MANAGEMENT ! Stabilise patient medically – lactulose, antibiotics,
liver diet – minimum 2 weeks prior to surgical therapy or planned anaesthesia for imaging etc ! Soy based proteins may be beneficial Proot JVIM 2009
! Omeprazole – lifelong 1mg/kg (Weisse JAVMA 2014)
! Levetiracetam – 20mg/kg tid 24 hrs pre op – 1 week post op (Fryer JVIM 2011)
! Phenobarbitone – ~5mg/kg bid (Tisdall JSAP 2000)
MEDICAL OUTCOMES ! Greenhalgh JAVMA 2010 + 2014 (16/124 IHPSS)
! MST medical management 2.3 yrs (27 dogs overall), surgery 8 yrs (attenuation, cellophane, ameroid)
! Medically managed dogs had higher incidence of recurrent clinical signs than surgically esp 4 - 7 yr period
! 20% > 6 year survival
! Watson JSAP 1998 (19/27 IHPSS) ! Avg age at euthanasia 20 months (65% IHPSS euthanased) ! IHPSS more likely persistent/progressive neuro and urinary
signs ! Prognosis (IHPSS and EHPSS combined) improved if
! Older age at time of onset ! EHPSS ! Higher initial BUN
SURGICAL APPROACHES
GENERAL PRINCIPLES OF SURGICAL APPROACHES TO IHPSS ! Midline celiotomy +/- caudal sternotomy and diaphragmatic
incision
! Mobilise lobes by transection of triangular ligaments
! CT A or mesenteric portovenogram
! Planning for total inflow occlusion may be necessary for right and central divisional shunts (max 16m Hunt 1996)
! Identify enlarged portal branch – other side may be under developed
! Ligate lobar arteries and biliary tree as needed for access to portal branches
! Right angle forceps very useful
GENERAL PRINCIPLES OF SURGICAL APPROACHES TO IHPSS ! Hepatic veins are very short and as such dissection of vessels
is usually attempted by dissection of parenchyma ‘away’ from the vena cava as acute laceration of vein/shunt generally leads to death
! Suture material typically 2-0 silk or non absorbable monofilament
! Post sinusiodal attenuation theoretically preferable however acceptable outcomes reported with pre sinusoidal
! If unable to completely dissect, can partially attenuate with mattress suture and pledgets
! If adequate dissection is possible, then cellophane or an ameroid constrictor can be placed
SURGICAL APPROACHES TO LEFT DIVISIONAL SHUNTS ! Post hepatic
dissection and ligation successful in most reports
! Dissect at level of left hepatic vein, or with ductus venosus as passes between the left lateral lobe and papillary process of caudate lobe
! Suture, cellophane band, ameroid constrictor
SURGICAL APPROACHES TO CENTRAL DIVISIONAL SHUNTS ! White 1998 – dissection through hepatic parenchyma or post
hepatic caval venotomy – risk of intra operative death
! Hunt 1996 – portal venotomy, caval venotomy
! Most are window type so consider intravascular
SURGICAL APPROACHES TO RIGHT DIVISIONAL SHUNTS ! Pre hepatic dissection
technique– Tobias 2003 ! May have thin, tough
layer of peritoneum connecting PV to CVC
! Caudate branch leaves shortly after bifurcation
! Hunt 1996 – portal venotomy, caval venotomy
SURGICAL APPROACH FOR COIL EMBOLISATION
SURGICAL ATTENUATION OPTIONS
SURGICAL ATTENUATION OPTIONS ! Suture ligation
! Complete or partial (~86%) ! Pre or post hepatic ! Intra or extravascular
! Ameroid Constrictor ! Pre or Post hepatic
! Cellophane band ! Pre or post hepatic
! Jugular Vein graft +/- ameroid constrictor
! Intra vascular coil occlusion (complete or partial)
! Hydraulic Occluder
SUTURE LIGATION ! Silk (2-0) typically used
! Papazoglou Vet surg 2002, White Vet Rec 1998
! Non encephalopathic dogs may tolerate complete
! Use intra operative measurements to guide degree of attenuation ! Max post ligation pressure 17-24cm H20 (White 46) ! Max change portal pressure 9-10cm H20 ! Max decrease CVP 1cm H20 ! Max decrease arterial pressure 5mmHg ! No dramatic increase in HR
AMEROID CONSTRICTOR ! Ameroid Constrictor
! Stainless Steel Outer ring with Casein interior
! Degree of attenuation from fibrous tissue and casein is variable (Hunt Vet Surg 2014)
! Larger rings may give less reliable attenuation
! Majority of closure 3-14 days
! Advantage – avoid acute occlusion of shunt
! Limited by ability to dissect vessel of interest ! Left divisional post hepatic ! Pre hepatic if able to dissect appropriate branch of portal vein
AMEROID CONSTRICTOR ! Bright Vet Surg 2006 ! 9 dogs and 1 cat ! Post hepatic application for left division ! Pre hepatic application (portal vein branch or shunt)
for R or central division ! No major peri operative complications, good outcome
4.5 yrs (2 died - 1 from shunt, 1 unknown)
! Mehl Vet Surg 2007
! Compares partial ligation (17 dogs) with ameroid (11 dogs) for left divisional post hepatic treatment
! Outcome superior in Partial ligation group (92% excellent) vs ameroid group (20% excellent, 50% good, 30% poor)
! Positive scintigraphy 7/8 PL vs 3/7 ameroid
HYDRAULIC OCCLUDER ! Adin JAVMA 2006 – 10 cases
! Use commercially available device designed for USMI (Norfolk Medical)
! Subcutaneous port allows gradual post operative attenuation by extra luminal compression
! Limited by ability to dissect and place device ! 8/10 normal at 22 month follow up ! 3/10 needed revision for leakage
CELLOPHANE BANDING ! Hunt Vet Surg 2004
! 11 dogs reported as part of case series of 106 ! 4 right divisional ! 6 left divisional ! 1 not recorded
! Attenuated to 3mm or less where possible either around the shunt itself or a pre hepatic branch of the portal vein
! 3/11 = 27% perioperative death
! 3/11 = 27 % immediate post operative complications – 1 neurological syndrome, 2 portal hypertension
! Survival with resolution of hepatic function abnormalities 50% (vs 84% EHPSS)
JUGULAR VENOGRAFT – Portal vein to CVC ! Kyles Vet Surg 2001 – 10 dogs
! Dogs unable to tolerate complete occlusion (increase of portal pressure > 8cm H20)
! Jugular autograft + ameroid constrictor placed ! Require use of anti coagulant ! Complete ligation in 8/10 dogs ! Clinical outcome excellent in 9 surviving dogs but 4/9 had multiple acquired
shunts
! Kyles Vet Surg 2004 – 7 dogs ! Used jugular autograft but did not place ameroid ! 6/7 died peri operatively – 1 long term survival ! Ameroid required to improve hepatic perfusion
! White Vet Rec 1998 ! Placed jugular graft prior to approaching shunt for dissection and attenuation with
subsequent partial attenuation of graft following complete ligation of shunt
! Gellasch JAVMA 2003 ! Placed jugular graft and then performed hepatic lobectomy
INTRAVASCULAR COIL EMBOLISATION ! Weisse JAVMA 2014 – 100 dogs (prospective)
! Discusses evaluation by intra operative angiography and portal pressure measurement followed by caudal vena cava stenting and coil embolisation of single or multiple intrahepatic portosystemic shunts
! Uses laser cut nitinol stent in CVC to stop migration of thrombogenic coils into venous and then systemic circulation
! Effectively a form of partial attenuation – further coils added depending on increase in portal pressure and gradient between portal system and caudal vena cava
! Major advantage is minimally invasive method and post hepatic location for occlusion of vessel
! Acute ligation described in some cases (NB Patient age and subsequent growth)
! Reported in cats
INTRAVASCULAR COIL EMBOLISATION ! Weisse JAVMA 2014 – 100 dogs (prospective) ▫ 14% had more than 1 procedure – recommend 1 month
withdrawal of medical support ▫ 3/95 had complete occlusion, ▫ 2/95 had sufficient pressure increase from stent alone ▫ 1 – 30 coils placed in others ▫ Mean coils – first 50 cases 3.5, second 50 cases = 8 ▫ Post coiling pressure – first 50 cases increase 1.4cm H20, second
50 cases = 6.3 cm H20 ▫ Stent and coils undergo fibrous incorporation
‘Team Approach’ ! High quality anaesthesia management
and manometry
! 24 hour ICU facility/quality medical support
! experienced CT interpretation
! 2 interventionalists/surgeons • extensive formal training/experience
in intra-vascular interventional procedures is advised
• understanding of hepatic vascular anatomy, haemodynamics and physiology
PROCEDURAL PLANNING
! CT Angiography – at diagnosis, repeated at >5 months of age – 2mL/kg under inspiratory pause
! Confirm vascular morphology
! Measure caudal vena cava
! Plan patient position
Caudal vena cava diensions
COMPLICATIONS AND OUTCOMES
COMPLICATIONS (1) ! PERI OPERATIVE DEATH (intra op + ~ first week) ! Coil Embolisation – 5%
! Suture Ligation 6-23%
! Ameroid Constrictor 0-29%
! Cellophane Band with attenuation 27%
COMPLICATIONS OF SURGICAL INTERVENTION (2) ! POST LIGATION NEUROLOGICAL SYNDROME ! Weisse 2014 – 6% (no pre op medication)
! Papazoglou – not reported
! Hunt 9% (1/11 – some use of phenobarb)
! White – 7/45 euth at some stage post operatively for neurologic signs (1/7 acute = 2%)
COMPLICATIONS OF SURGICAL INTERVENTION (3) ! Acute portal hypertension – uncommon complication of post
hepatic partial attenuation techniques
! Ascites
! Haemorhage
! Coagulopathy (NB venograft techniques)
! Gastro intestinal ulceration – Weisse recommends life long omeprazole 1mg/kg sid (reduced post op mortality rate from 30% to 4%)
! Open surgery up to 39% complication rate 72 hrs
! Weisse – 19% post op complications, 13% major (6% HE)
ACQUIRED SHUNTING AND PERSISTENT FLOW (1) ! Partial attenuation occurs with many forms of
treatment (suture, coil), and evidence of persistent shunting is common with gradual attenuation methods (Hunt, Bright)
! Intrahepatic collateral circulation forms in many cases after surgery " aim is to adequately perfuse the liver
! Limit to pressure increases either due to congenital portal under development/hypertension or acquired hepatic changes with chronic shunting
ACQUIRED SHUNTING AND PERSISTENT FLOW (2) ! Target pressures are unclear – post hepatic
attenuation with buffer/compliance provided by hepatic parenchyma (post sinudoidal) vs traditional extra hepatic pressure with portal pressure increases buffered by small intestine, pancreas etc – unclear what recommendations are
! Intra operative angiography most sensitive diagnostic (preferred over CT A)
! Furneax recommends lobectomy – low rate of complete attenuation so unlikely to be feasible in many cases at first surgery
PROGNOSTIC FACTORS – Clinical Pathology ! Papazoglou 2002
! Body weight >10kg = more likely to survive initial surgery ! Anaemia ! Increased BUN ! Increased WCC or NP count ! Greater pre operative alb/TP = better survival ! LT survival better if TP > 4 g/dL
! Weisse 2014 ! Univariate- lower globulins, lower TP, lower resting and post
prandial bile acids ! Multivariate – increase in globulins and total solids ! Dogs with successful outcomes tended to normalise hepatic
function parameters ! Bile acids only examined in 25% patients as persistent shunting
expected
PROGNOSTIC FACTORS – Shunt Location ! Unusual breeds more likely inoperable/unusual shunt
(Hunt AVJ 2004)
! Papazoglou 2002 ! shunt location not prognostic (extravascular suture ligation)
! White 1998 ! 6/15 (40%) central divisional died intra operatively or post
op portal hypertension
! Weisse 2014 ! Not statistically significant but possible effect of location
(Central 80% > Right 67% > Left 48% for excellent outcome)
! Multiple shunts no difference
EVIDENCE BASED OUTCOMES AUTHOR CASES CASES
FOLLOWED UP
FOLLOW UP TIME
ACCEPTABLE OUTCOME
WEISSE 100 98 (98%) 36m 81% WHITE 45 37 (82%) 21m 69% PAPAZOGLOU 32 22 (69%) 13m 55% MEHL 28 26 (93%) 28m 70% (ARC)
-100% (PL) BRIGHT 9 9 (100%) 38m 89% KYLES 10 9 (90%) Up to 12m 90% HUNT 11 10 (91%) unknown 50%* ADIN 10 8 (80%) 22m 80%
CATS • Lipscomb Vet Rec 2007 ▫ 13 cats as part of group of 49 PSS (partial or complete suture atten) ▫ 8 left division, 3 R, 2 central (intra op mesenteric portography) ▫ 75% overall good-excellent outcome – results not segregated ▫ 36% post op neurological signs (IHPSS not more likely than EHPSS) ▫ 2 peri op deaths
• White Vet Rec 1996 ▫ 6 cats – 4 left divisional, 1 central, 1 R (intraoperative mesenteric
portography) ▫ Partial attenuation (5 cats) or complete (1) ▫ 4 good outcome, 1 good but on medication, 1 died
• Lipscomb JAVMA 2009 ▫ 4 cats – 3 left divisional, 1 central (group of 29 PSS) ▫ Treated with partial attenuation following mesenteric portography ▫ Outcome not segregated from EHPSS (25 cases) ▫ Cats with better developed portal vascular tree had more predictable
resolution of clinical signs and lower rates of post surgical neurological signs • Bright Vet Surg 2006 – 1 cat with ameroid contrictor of left divisional –
good outcome • Weisse JAVMA 2002 – 1 cat coil embolisation – good outcome
QUESTIONS?
PORTOSYSTEMIC SHUNTS
! Abnormal vascular connection between portal and systemic venous systems (congenital vs acquired)
! Congenital are typically a solitary vessel • Intrahepatic (from intrahepatic portal vein branch
to hepatic vein or caudal vena cava) – 25-33% • Extrahepatic (from extrahepatic portal vein or
tributary to caudal vena cava or azygous vein) – 66-75%
! Association with typical histologic changes of hepatic parenchyma
ANATOMY (1)
! Hepatic parenchyma perfused by hepatic artery (20% volume, 50% oxygen) and portal vascular system (80% volume, 50% oxygen)
! Hepatic artery has right lateral, right medial and left branches, with various sub branches
EMBRYOLOGY (1) ! Embryologic development of abdominal venous
system from Vitteline, umbilical and cardinal system
! Vitteline system – R and L from yolk sac to sinus venosus ! Venous plexus forming sinusoids ! Cranial part of Right vitelline vein becomes hepatic
CVC ! Caudal L and R vitelline veins become portal vein
EMBRYOLOGY (2) ! Embryologic development of abdominal venous
system from Vitteline, umbilical and cardinal v
! Umbilical system – allantois to sinus venosus
! Umbilical veins enter portal vein at sinus venosus ! Portions contribute to sinusoid development ! Ductus venosus = shunt between sinus venosus and
CVC (most blood bypasses sinusoids) = left umbilical vein
! Ductus venosus closes functionally 2-6d, structurally by 3w (see later)
EMBRYOLOGY (3) ! Embryologic development of abdominal venous
system from Vitteline, umbilical and cardinal v
! Cardinal system
! Eventual anastamosis with R vitteline vein to form CVC
! Other portions from abdominal components of azygous and hemiazygous
AETIOPATHOGENESIS (1) ! Developmental errors can produce abnormal
connections between cardinal and vitteline systems (= extrahepatic portocaval and portoazygous shunts)
! Extrahepatic and Right or central intrahepatic portocaval shunts may result from persistent connections between caudal and R Cranial segments of the vitteline system, or malformation of hepatic sinusoids
AETIOPATHOGENESIS (2) ! Concurrent portal microvascular under
development " increased resistance to portal vein flow " persistence or opening of vestigial or anomalous vessels
AETIOPATHOGENESIS (3) – Patent Ductus Venosus ! Umbilical vein and extrahepatic portal vein
terminate at portal sinus
! Ductus venosus arises from portal sinus and travels between L lateral lobe and ventral aspect of papillary process of caudate lobe to ampulla (Ductus venosus, left hepatic and left phrenic v)
! Functional closure 2-6 d (breed variation)
! Structural closure by 3w (connective tissue proliferation from portal sinus to ampulla)
AETIOLOPATHOGENESIS (4) – Patent Ductus Venosus ! Mechanism of closure unknown ! Changes to flow conditions (umbilical v) ! Functional ridge that responds to endothelin, Cy
P450 and TXA2 (lambs) ! No discrete sphincter in puppies
! Failure of closure mechanisms ! Vascular resistance from parenchymal
microvascular under development (increased sinusoidal pressure)
! Failure of response to endothelin etc
EPIDEMIOLOGY ! Single IHPSS 25-33% of PSS in dogs and cats
(Tobias 2003)
! IHPSS more frequent in large breeds
! Golden Retriever, Labrador Retriever, German Shepherd Dog, Bernese Mountain Dog, Australian Cattle Dog, Australian Shepherd
! Irish Wolfhound – Patent Ductus Venosus
PATHOPHYSIOLOGY ! Portosystemic shunting leads to reduced liver perfusion
and therefore function " reduced toxin clearance, drug metabolism, reticuloendothelial dysfunction, altered fat metabolism, progressive liver failure
! IHPSS typically large vessel/high volume shunt " clinical signs at a young age
! Manifests as hepatic encephalopathy, GI signs, LUT signs, recurrent infection, coagulopathy, delayed growth
! Dogs with clinical hepatic encaphalopathy have a procoagulable state (Kelley JVIM 2013)
! Multiple acquired shunts can develop secondary to portal hypertension (intra and extrahepatic)
CLINICAL PATHOLOGY ! CBC/MBA – reduced hepatic function parameters
(proteins – alb/glob, BUN, cholesterol, glucose), increased hepatic enzyme activity, microcytic anaemia
! Bile acid stimulation/ammonia tolerance
! Urinalysis ! Dilute ! Presence of urate crystals (up to 57% dogs, 42%
cats) ! proteinuria
CLINICAL SIGNS ! CNS signs - up to 90% - highly variable ! Correlate with meal ingestion up to 50% ! (anaesthesia intolerance)
! GI signs – up to 30% dogs ! Vom, Diarrhoea, anorexia, pica, GI haemorrhage ! Cats – ptyalism up to 75%, other GI signs less
! Urinary Signs – up to 53% ! PU/PD – reduced medullary gradient (BUN),
psychogenic with HE ! Haematuria, dysuria, stranguria, pollakiuria ! Urate urolithiasis
! Others ! Cryptorchidism, heart murmur ! Copper coloured iris (cats)
DIAGNOSIS (3) ! MRI Angiography ! Can have high diagnostic rate however need high
power MRI (1.5T) and optimised protocols (Mai VRU 2011, Brueschwein VRU 2010)
! Scintigraphy ! Excellent for identifying presence of shunt, weak at
localising
! Radiography ! Limited to hepatic volume estimates and renal size
! Intraoperative Contrast portovenogram ! As part of intravascular technique (caval) ! As part of extravascular technique (mesenteric or
splenic)
IMAGING (2) ! Abdominal ultrasound – high sensitivity (95-100%)
for IHPSS due to parenchymal contrast ! 92% sensitive for intra vs extrahepatic ! Good for cystoliths ! EHPSS (Sens 47-95%, spec 67-100%)
! CT Angiography ! Gold Standard for IHPSS, EHPSS, multiple acquired
EHPSS, other abdominal vascular anomalies ! Identifies cystoliths ! Kim VRU 2013 CT A vs Ultrasound for EHPSS
! CTA more sensitive (96 vs 68%) with similar specificity (89 vs 84%)
! CTA higher accuracy for origin and insertion of vessel ! CTA better for multiple acquired shunts ! Requires GA, not as reliant on operator ability
LONG TERM OUTCOMES ! WEISSE - 66% normal, 81% normal but with dietary/medical management
! Left division – 47% excellent ! Central – 80% excellent ! Right – 67% excellent ! Good or excellent outcome = 6- 7 yr survival, poor = 2-3 yr – 40% long term
survival if good or poor outcome, overall MST 6 years, med FU 3 yrs, 98/100 followed up
! Multiple shunts no difference ! AMEROID – Good – Excellent Mehl 70% 10/11 dogs, median 28 m, Bright –
7/9 dogs and 1 cat alive no CSx or diet change median 38m post op ! SUTURE – Good – Excellent 76-100% (White = 21m FU 21/45 alive, Mehl
good-excellent 100% of 13/17 available for FU) ! PAPAZOGLOU – 1 year survival 60%, 2 year survival 55% (suture ligation/
partial). MST 36 months Mean FU 13m ! KYLES – most dogs examined 8-10 weeks post op, re checks up to 52
weeks ! ADIN – 8/10 good long term outcome (22 month FU (2 LTF)) ! HUNT – 50% good long term outcome (no persistent clinical signs or peri
operative death) – strict reporting of FU time not available