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