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Krishna Chowdary

The document provides an overview of liver anatomy and physiology. It discusses the liver's blood supply from the hepatic artery and portal vein. It describes the microscopic structure of the liver in lobules and hepatic sinusoids. Key functions of the liver mentioned include bile secretion, with bile salts and lipids concentrated in the gallbladder. The roles of hepatocytes, Kupffer cells, and other liver cells are summarized.

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LIVER - 1
• LIVER ANATOMY • LIVER PHYSIOLOGY • LIVER FUNCTION TESTS – ENZYMES, ESTIMATION OF REMNANT • RADIOLOGY – SEGMENTS • DILI; CHOLESTASIS • ALF, LIVER SUPPORT SYSTEMS • ISCHEMIC HEPATITIS • HEPATIC TRAUMA • HEPATIC CYSTS • HYDATID LIVER • LIVER ABSCESS – ALA, PLA; • HEPATIC BENIGN NEOPLASMS
• Invested with peritoneum except posteriorly • Posteriorly - peritoneum reflects onto the diaphragm – forms R & L triangular ligaments.
• RHV - largest – short extrahepatic course – 1- 2 cm • LHV & MHV – drain separately/ common venous channel 2 cm long – to L of IVC, infra- diaphragmatically • Umbilical vein- MC single - • runs beneath falciform – btw MHV & LHV – into - into – LHV(MC)>MHV> Confluence • 15% patients - accessory RHV - present inferiorly • Caudate lobe – HV drainage -directly into the IVC
• R portal triad – short extrahepatic course - 1 - 1.5 cm • L portal pedicle - 3 - 4 cm beneath segment IV – separated fron segment IV by Hilar plate (connective tissue) enters umbilical fissure • branches of L portal pedicle – supply segment II segment III, recurrent(feedback) branches to segment IV • Beneath segment IV - pedicle has – LPV, LHD – Joined by LHA later at the base of the umbilical fissure
• 3 Portal Scissurae (PS) – with HV – divide liver into 4 sectors (Couinaud)/ Segments(Goldsmith)/ Sections(IHPBA, Brisbane) - each sector receives a portal pedicle. • MPS – has MHV – Cantlie line – divides liver into R & L • RPS – Has RHV – R liver into RA Sector, RP Sector • LPS – not in umbilical fissure – inside liver, carries LHV; Umbilical fissure has Portal pedicle
CAUDATE LOBE • Anterior surface within parenchyma - covered by posterior surface of segment IV the limit an oblique plane slanting from the LPV to LHV. • Constant L portion (Spheigel lobe/Papillary process) & variable R portion(caudate process/segment IX) (size).
CAUDATE LOBE • Major blood supply – arises from left branch of LPV & LHA close to base of umbilical fissure • The hepatic veins (MHV, LHV) -short in course – drain from caudate directly into the anterior & left aspect of IVC
CAUDATE LOBE • Anterior to IVC • Posterior to PV • B.S – mainly by LPV • Occasionally, br. From MPV
CAUDATE LOBE • Caudate mobilisation from Left side • Caudate branch of portal V, Veins from IVC – divided • Tunnel between the MHV - LHV & IVC – to clamp
CAUDATE LOBE • Various approaches to Caudate lobectomy • Lesser omentum opened – Caudate Br of LPV divided • Ligamentous attachments of caudate lobe divided – Retrohepatic V divided – Caudate this approaches from left / Right
CAUDATE – BLOOD SUPPLY, VENOUS DRAINAGE • Caudate Blood supply, biliary & venous drainage – from R and L portal triad. • The RCL including the caudate process, predominantly receives PV blood from RPV/ from MPV bifurcation. • LCL - portal supply - from the LPV exclusively. • Arterial supply & biliary drainage of the RCL - most commonly associated with RPS vessels; LCL blood supply and biliary drainage – with L main vessels. • HV drainage of caudate - unique - the only hepatic segment that drains directly into IVC. • Some Veins from R Posterior section and caudate lobe drain directly into the IVC. • Can sometimes drain into posterior aspect of IVC if a significant retrocaval caudate component is present.
PORTAL VEIN • PORTAL VEIN • High flow, low pressure (No valves – PV press measured anywhere along PV) • 75% of Liver BF, but 50 – 70% of Liver O2 reqt(due to high flow) • 5.5 – 8 cm long, 1 cm diameter; • Formation – behind pancreas neck – SMV, splenic V • Inside lesser omentum – receives coronary V • Larger RPV (RA, RP, Caudate process), smaller LPV(Caudate br. Before umbilical fissure; • Most constant anatomy among portal triad
HEPATIC ARTERY • HEPATIC ARTERY • 25% of the Liver BF, 30 - 50% of oxygenation. • High flow, high pressure • RHA – usually posterior to CHD – enters Calots – gives cystic A • LHA – into umbilical fissure; to the R of fissure – gives segment IV A • Hepatic A anatomy – Highly variable
H.A VARIATION • Variations – • Accessory vessel – in addition to original • Replaced vessel – substituting original vessel • Replaced/Accessory RHA – from SMA – 11- 21% • Replaced/Accessory LHA – from LGA – 4-10% • GDA – from – CHA/RHA • Cystic A – anywhere from Coeliac axis to RHA Michelles classification I Normal Anatomy II Replaced LHA from LGA III Replaced RHA from SMA IV Replaced RHA & LHA V Accessory LHA VI Accessory RHA VII Accesory RHA & LHA VIII Replaced RHA/ LHA with other hepatic artery being an accessory one IX Hepatic trunk as a branch of the SMA X CHA from LGA
• NERVE SUPPLY • Sympathetic fibres from T7 - T10  through coeliac ganglia • Parasympathetic fibers from both vagal N • R sided Coeliac ganglia & R Vagus  Anterior hepatic plexus – along hepatic A • L sided coeliac ganglia & L Vagal N – Posterior Hepatic plexus – posterior to BD, PV • Hepatic A – sympathetic; BD and PV – parasympathetic • LYMPHATICS • HDL; Hepatic A  Coeliac LN  Cysterna chyli • OR • HV  Suprahepatic IVC/ Diaphragmatic hiatus
MICROSCOPIC ANATOMY • Hepatic parenchyma - microscopic functional units – acinus/ lobule • Central terminal hepatic venule (HV) surrounded by 4 – 6 terminal portal triads (PT) - polygonal unit • PT – in connective tissue – space of MALL • Btw HV & PT – Hepatocytes – in one-cell-thick plates - surrounded on each side by sinusoids. • Blood flow – PT  HV • Bile flow – Biliary canaliculi (lateral walls of hepatocyte)  Bile ducts  PT
• PV, Hepatic Arterioles(HA) – blood supply to sinusoids • PV & HA flow inversely varies in sinusoids • Sinusoid BF - PV component – constant, minimal; HA component – pulsatile, low volume • Sinusoids - 7 -15 μm wide - can increase in size by up to 10-fold  low-resistance and low-pressure (2 -3 mm Hg) • Zones – 1, 2, 3 – from PT  HV • Zone 1 (periportal) – high nutrients, oxygen. • Zone 2 (intermediate) • Zone 3 (perivenular) - low oxygen, nutrients
• Space of (SD)– perisinusoidal space – exchange of proteins, plasma components btw Hepatocytes, sinusoids. • Endothilial cells in SD – lack BM, Inter-cellular junctions; have fenestrations – Bidirectional mmt of high, low molecular wt solutes
Cells of Liver Hepatocyte(HC) Kupffer cell Stellate cells(Ito cells) NK cells, CD4, CD8 cells 60% of hepatocellular mass, 80% of cytoplasmic mass Line sinusoids among endothelial cells In Space of Disse Innate immunity in liver Has surface contact with – Adjacent hepatocytes,bile canaliculus & perisinusoidal space Phagocytic High retinoid content Sinusoidal membrane- microvilli – with Disse – blood- HC solute exchange Migrate along sinusoids to injury site vitamin A storage/ synthesis of collagen, ECM proteins Lateral domain – HC-HC interface - intercell communication Initiate inflammation Change to myofibroblastic phase in liver injury (less vit A production, more ECM, cellular contractility Canalicular membrane – HC- canaliculi interface – Zona occludens Express MHC II Ags Progression of fibrosis to cirrhosis
HEPATOCYTE MICROSOMAL FUNCTION • Hepatocyte Mt – 1000/cell; 20% of cell mass; ATP via oxidative phosphorylation; Fatty acid oxidation; • HePar-1(Hepatocyte Paraffin-1) – Antigen on hepatocyte Mt – Hepatocyte Trs • Hepatocyte microsomal fraction – interconnected membrane complexes – SER, RER, Golgi complex – Lipid, glucose metabolism, protein synthesis, cholesterol prodn & metabolism • Function of hepatocytes – dependent on their location in the 3 zones in lobule – FUNCTIONAL HETEROGENEITY • BUT – Under specific physiological conditions – functions can change irrespective of anatomic location
ZONES IN LIVER FUNCTION Zones Feature Hepatocye function 1 (Periportal) High substrate conc. Narrow, tortuous sinusoids High O2, solute uptake Glucose Uptake & release, bile formation, Albumin & Fibrinogen synthesis 2 (Intermediate) 3 (Perivenular) Most susceptibe to hypoxia Sinusoids– Larger fenestrations Larger molecule uptake Glucose catabolism, xenobiotic metabolism, AFP, α1-AT Urea cycle enzymes
BLOOD SUPPLY TO LIVER • Dual B.S – PV(75% of LBF, 50-70% of O2, though partly de-oxyganated) HA – 25% of LBF • LBF - Reduced in exercise; increased after ingestion of food. • Oxygen conc. – max(85%) in fasting state • Carbohydrates – most profound effect on LBF • Pressure – HA (=systemic BP); PV – 6-10 mm Hg, Sinusoids – 2-3 mm Hg • Factors controlling LBF – ANS, hormones, Bile salts, metabolites; Endogenous subst • As portal perfusion decreases, hepatic arterial flow generally increases (Hepatic Arterial buffer response – LAUTT et al) – by Adenosine washout • HABR - capable of buffering 25% to 60% of the decreased portal flow; increases LBF by 30%
HEPATIC VEIN • Free pressure in HVs & IVC - 1 to 2 mm Hg; 1 - 5 mm Hg lower than sinusoidal & PV pressure • Portal pressure gradient, defined as the difference in PV and IVC pressures - • Pressure gradient in the liver is thus extremely low - 5 mm Hg
PHYSIOLOGY OF HEPATIC SINUSOIDS • Hepatic sinusoids – • Absent BM • Endothilial lining with fenestrae(arranged in clusters of 10-50 pores– sieve plates) • Fenestrae –contract & dilate in response to sinusoidal BF changes • HSC – Ito –(Space of Disse) - compress sinusoids by squeezing endothelial cells - ctrl BF through sinusoids • KC (Luminal side) - Secrete large amounts of vasodilator NO
• Regarding Portal BF All are true except – a. Ito cells causes contraction of sinusoids b. Endothelin & Endothilium derived NO – cause contraction of sinusoids c. Smooth muscle cells of endothelium cause contraction of sinusoids d. Sinusoids and portal venules are sites of resistance
Endothelial mediators controlling vascular tone by acting on HSC contractility agent Function Source Target TXA2 VC, plt Activation, aggregation, leukocyte adhesion SEC, KC SEC, platelet, leukocyte PGI2 VD,platelet aggregn inhibn SEC SEC, HSC AT-II VC HSC HSC NO VD (i NOS) VD(e NOS) SEC, KC, VSMC,HSC, HC SEC VSMC, HSC VSMC, HSC ET1 VD SEC, HSC, KC VSMC, HSC, SEC, KC ET1 VC SEC, HSC, KC SEC CO VD SEC, KC, VSMC,HSC, HC VSMC, HSC H2S VD HSC, HC VSMC
• Liver-extrinsic NO - vasodilation in the hepatic arterial & mesenteric vascular beds. • Endothelin - prolonged generalized systemic constriction + direct effect on LBF. • Endothelins reduce hepatic perfusion; increase portal pressure; reduce sinusoidal diameter • Angiotensin - decreases hepatic arterial & portal blood flow - significant vasoconstrictor • effect on the HA. • H2S endogenously or exogenously - reverse the norepinephrine-induced vasoconstriction • SYMPATHETIC NS - HA - both α-adrenergic, β-adrenergic receptors; PV - only α-receptors • Low doses, epinephrine  hepatic & mesenteric arterial vasodilation; high doses,vasoconstriction
FUNCTIONS OF LIVER – BILE SECRETION • Water – 85% of bile • Major Organic solutes in bile - bilirubin, bile salts, phospholipids, cholesterol. • Bilirubin – RBC breakdown product • Bile salts(BS) – Steroids – by hepatocytes • Primary (80% of BS) – Cholic, Chenodeoxycholic • Secondary – Lithocholic, Deoxycholic • Phospholipids – by liver – Lecithin MC form(95%) • Cholesterol – 80% synthesized by liver • Normal bile – 750 – 1000 ml/d Stimulate bile flow Inhibit bile flow Vagal stimulation Splancnic stimulation Secretin, CCK, gastrin, and glucagon Major important – rate of hepatocyte Bile Slt synthesis
BILE COMPOSITION • Lipids, bile salts, phospholipids, cholesterol - concentrated in the GB
BILE SALT, LIPID SECRETION Na dependent Na independent ABC-11 PFIC Phospholipid
• Bile acid (BA) – synthesized from cholesterol – CLASSIC(cholic acid), ALTERNATIVE(Chenodeoxycholic) Pathways • BA – from Disse space to hepatocyte • OATP(Organic Anion Transport Protein) – wide substrate affinity, transport many organic ions • OATP-C - major Na-independent BS uptake system • OATP-A - bile acids uptake; OATP- taurocholate uptake. • Rate limiting step in BS secretion – BS transport across canalicular membrane • ABC-11 – Major transport of monovalent BS into the canaliculus • MDR-related protein-2 (MRP2) – transports sulfated, glucuronidated BS into canaliculus – also organic anions, toxins, heavy metals, ABs • Progressive familial intrahepatic cholestatis type 3 - MDR3 deficiency - no phosphatidylcholine in bile – no mixed micelle formn with bile salts – injury to biliary epithelium by BS - resulting in neonatal cholestasis, cholestasis of pregnancy, cirrhosis
ENTEROHEPATIC CIRCULATION • Circulating bile pool - total amount of bile acids in EHC • 95% of bile salts – reabsorbed; extracted by hepatocytes • Colon – Bacterial action on primary BS  Secondary BS(Deoxy, litho) • Active steps involved in EHC – Secretion of bile acids from hepatocytes into canaliculi; from ileum/small bowel into Portal Vein • Bile acids – passively absorbed in jejunum • Function of EHC – reusing BA/ Excretion of cholesterol/Absorption of dietary dats, Fat soluble vtamins
BILIRUBIN METABOLISM • Heme breakdown – • early phase - accounting for 20% of bilirubin – is from hemoproteins - occurs within 3 days of labeling with radioactive heme • late phase - accounting for 80% of bilirubin - from senescent RBCs – within 110 days • Heme  Green BV(Heme oxygenase) Orange BR(BV reductase) • Circulation – BR-Alb complex  dissociates in Disse space  Free BR into HepatocyteConjugation(UDP Glucuronidase)into bile canaliculi(energy dependent)GIT Deconjugn(bacteria) • Urobilinogens Oxidation into BS Reabsorption  EHC/spillage to urine • Kernicterus – encephalopathy/cochlear damage in neonates – Unconjugated Unconjugated HyperBR Conjugated HyperBR Neonatal; Hemolytic anemia, Enzyme def – Gilbert, Criggler Najjar Cholestasis, Rotor, Dubin Johnson
CARBOHYDRATE METABOLISM • Storage, distribution of glucose to peripheral tissue • Storage of glucose as glycogen – Liver, muscle • Breakdown into glucose from glycogen– only by liver • 65g/kg liver – glycogen store; used in post- absorptive state – depleted after 48 hpurs • > 48 hrs – liver shifts to gluconeogenesis – alanine(muscle); glycerol(adipose) • Cori cycle -
COAGULATION • Synthesize coagulation factors, fibrinolytic system compnents • Vitamin K absorption, Vitamin K–dependent coagulation factor synthesis • Gamma carboxylation of • Thrombocytopenia, platelet abnormalities, vitamin K deficiency; DIC • Warfarin – acts on liver - blocks vitamin K–dependent activation of factors II, VII, IX, and X. • Hepatic synthetic dysfunction – Abnormal PT/INR
IMMUNOLOGY • INNATE – Initial, non specific defence; NK, PMN, DC, Mac, complement, epithelial barriers • Direct kill Tumor/Infectious cells – present Ag to Acqd immunity • ACQD – Later, specific targeted – B cell, T cell MAC PMN NK DC B Cell CD4 CD8 INNATE ADAPTIVE 0 – 12 Hrs 1 – 5 days
• APC signals to B/T Cells • Signals from APCs – Antigen presentation; Co- stimulation; Cytokine release • Naïve CD4+ T cells – differentiate into T cells—Th1, Th2, Th17, and Treg • Programmed CD4+ T cells - modulate CD8+ T cells - differentiate into cytotoxic / regulatory cells.
• Liver – Tolerance v/s excessive immunity balance • Tolerance - oral tolerance, chronic hepatitis infection, Tx • Drawback of tolerance - distant metastatic disease MC deposited in liver . • Excessive immunity - AI Hepatitis, PSC, PBC. • Immune responses to intrahepatic Ags – if - effector CD4+, CD8+ T cells - not suppressed by regulatory T cells (Treg) OR Immuno- inhibitory pathways (PD1/PDL1) • Tolerance – if Treg/ PDL1/PD1 upregulated
CELLS • DC • Myeloid (CD11b+)/ lymphoid (CD8α+) liver DCs (10% of liver DC) - activate T cells, • Remaining DCs(90%) - low-to-no expression of CD11b & CD8α poor T-cell stimulators. • Human liver DCs - weaker stimulators of T cells; produce antiinflammatory cytokine interleukin-10 (IL-10) • KCs • Liver Macrophages • largest pool of macrophages in the body - from monocytic precursors • Location - hepatic sinusoids; also can migrate through space of Disse to interact with hepatocytes. • Antigen presentation, portal venous tolerance. • induce immune tolerance to liver allografts
• LSECs • Fenestrations -facilitate the selective passage of Ags btw sinusoid and hepatocyte; • LSECs - capable of capturing various Ags in vivo & in vitro • But cant activate T cells in the absence of exogenous costimulation
• Type of APC & presence/absence of costimulatory molecules – determine whether a T cell has no response (anergy) or is activated • Ag presentation by APC to T cell  trigger adaptive immune response unless suppressor cells or immunoinhibitory signals intervene.
LIVER FUNCTION TESTS • MARKERS OF CELLULAR INJURY • ALT(Cytoplasm; liver only) – More specific of liver injury >AST(Mt; not only in liver) AST or ALT 100s Mild viral hepatitis >1000 Acute viral hepatitis >3000 Acetaminophen, ischemic liver injury AST or ALT >300 IU/mL, AST/ALT>2 ALD ALT>AST NAFLD/Viral hepatitis AST>ALT Hypoxic/Toxic ALT t1/2 – 17 hrs AST t1/2 – 47 hrs ALT > AST Recovery phase AST significantly raised than ALT Extrahepatic source - myocardial infarction, rhabdomyolysis, strenuous exercise, hemolysis
LIVER FUNCTION TESTS • BILE FLOW MARKERS – • Alk Phos – Zinc metalloproteinase – by hepatocyte canalicular membrane • Also - bone, intestine, placenta, kidney, WBC • Increase – childhood(Bone growth); Old age(Bone resorption) • Alk Phose >/= 3 fold –BD obstruction/ Intrahepatic Cholestasis • GGT – non specific; monitor alcohol abstinence if AST, ALT Normal Acute cholestasis Bile duct obstruction Drug-induced cholestasis – Macrolide ABs, Azole antifungals Sepsis-induced cholestasis Parenteral nutrition–related cholestasis Critical illness–related cholestasis Chronic cholestasis Primary biliary cholangitis Hepatic sarcoidosis PSC, IgG4 - cholangitis Drug-induced cholestasis - Chronic bile duct obstruction
• SYNTHETIC FUNCTION Albumin T1/2 – 20 days Significant reduction Prolonged/mjor liver d/s PT – (PTThrombin) severe liver dysfunction, dietary vitamin K deficiency, antibiotic administration, vitamin K malabsorption, DIC, drugs (warfarin)
HEPATIC FUNCTION ASSESSMENT • VOLUMETRIC • required to assess FLR prior to major ( >4 segments) liver resection • MC – CT/ MRI • FLR volume = FLR/TLV; TLV includes Tumor volume – (apparently high TLV & low FLR) • So – TELV(Total estimated liver vol) – TLV for BSA • FLR/TELV = sFLR • TELV (i.e., sFLR) - better predictor of postoperative hepatic insufficiency • Exact volumetric threshold? • Normal background liver – 20-30% • Post chemotherapy – 30% • Known liver d/s – < 40% - indication for PVE • DH < 20%/ KGR - < 2.6% /wk-
• FUNCTIONAL ASSESSMENT • Hepatocyte injury – AST, ALT, ALP • Synthetic – Alb, INR • Hepatic metabolism marker – BR • CHILD TURCOTTE PUGH  CHILD PUGH • Developed to predict the risk of death in surgery for portal hypertension • Now – risk in cirrhotics undergoing varous procedures • 3 Lab tests (BR, Alb, INR) 2 Clinical findings – Ascites, enceph) • If no cirrhosis – CTP will be normal – alternative scores needed • Marker of global liver function in cirrhosis • Patient selection of for liver resection in HCC. • Class A cirrhosis - Sx • Class B – Approached cautiously • Class C cirrhosis – Avoid Sx
• MELD – • Initially – prediction of short-term survival in h cirrhotics; now – longterm survival also • Used in LTx to allocate organs. • In Cirrhotic/Partial hepatectomy – MELD >8 – predicts peri-op mortality, less long term survival • If no background liver injury – not useful • HEPATIC UPTAKE, METABOLISM, ELIMINATION • ICG – water soluble dye • Cleared from circuln by liver – Hepatocyte uptake, biliary excretion • IV inj.  ICG levels @ 5 min, 15 min • Measured as - ICGR15/ ICG-PDR/ICG - k • ICGR15 >14-20% - assctd with PHLF/complicns • Limitations – Not reliable in Hyper BR/ Intrahepatic shunting/ sinusoidal capillarization; • ICG – not remnant specific – only global liver function
NUCLEAR IMAGING FOR LIVER FUNCTION MODALITY RATIONALE ADVANTAGE LIMITATION Tc99m-GSA(Galactosyl Serum Alb)(glycoprotein analogue) scintigraphy Binds to hepatocyte receptors CLD – reduced hepatocyte receptors plasma glycoprotein increased Provides anatomic and functional information ?Specific to remnant liver function if combined with SPECT High interrater interinstitution variability Limited availability No measure of regional liver function HBS with Tc99m Mebrofenin[IDA(Imino- diacetic Acid) derivative] Metabolized by liver correlates well with ICG Good marker of post resection liver function
Other measures of metabolic function (lidocaine, galactose, 13C breath tests) Metabolized almost exclusively by the liver (P450) Poor clearance  liver dysfunction Correlated with other measures of total liver function Not widely available High interrater variability Time consuming Not specific to remnant Altered based on environmental conditions MRI with Gd-EOB-DTPA Contrast(50% excretion in N liver) Taken up and cleared by Hepatocytes Poor uptake  liver dysfunction Routinely available Assessment specific to remnant liver Not directly correlated with postresection clinical outcomes Galactose elimination test Accurately reflects metabolic function of the liver Altered based on envtl conditions US Transient elastography Provides assessment of liver fibrosis Noninvasive Fast User dependent Not correlated with clinical outcomes Gold standard remains volumetric-based assessment of the FLR with cross-sectional imaging (CT or MRI).
• DRUG INDUCED CHOLESTASIS Bland cholestasis Anabolic steroids, some antiandrogens, OCPs, Azathioprine, cetirizine, glimepiride, infliximab, metolazone, tamoxifen, warfarin Inflammatory cholestasis Penicillins, Macrolides, Sulfonamides, Tetracyclines, Antivirals, TCAs, BZDPs, Antipsychotics Vanishing Bile duct syndrome Psychotropes, ABs, NSAIDs Sclerosing cholangitis Chemo(Floxuridine), Intralesional agents – Absolute Alcohol, HTS, Iodine
ALF • Acute liver injury • Coagulopathy (iNR>/= 1.5) • Encephalopathy • Duration < 26 wks • No P/H/O liver disease • ETIOLOGY • Drug iduced • Acetaminophen – (dose>12g/d, but even at 3- 4g/d); intermediate NAPQI uses up glutathione • Centrilobular hepatocyte necrosis • Others • Antimicrobials MC ATT – Less favorable clinical response • VIRAL • HAV(3%), HBV(7%) – 10% of ALF • Others – • Indeterminate(12%), AI(7%), ischemic(6%) Wilsons(1%) HAV HBV Sptneous recovery 58% 24% OS 87% 69% Rx Supportive Antiviral
ALF – MEDICAL MANAGEMENT Grad e I HE changes in behavior, Normal consciousness level Out of ICU set-up Grad e II HE disoriented, delayed mentation, asterixis ICU; GCS/Unresponsiveness score charting CT brain – R/O SDH b4 ICP monitor insertion Enteral/Parenteral nutrition; electrolytes Avoid sedation III In & out of consciousness, confusion ICP monitor(controversial), ETT, If ICP to be – INR < 1.5; ICP in place – INR< 3 CPP - > 60 mm Hg; 30 degree head elevation; If AKI with III/IV HE – vasopressin – MAP; Prophylactic HTS – Na – 145- 155 Increased ICT – Mannitol  Hypothermia Vasopressors – MAP - CPP Continuous veno-venous HD for AKI
• UNOS 1A urgent waiting list pt • > 18 yrs • < 7 days’ life expectancy without LTx • Onset of HE within 8 weeks • No pre-existing liver disease • Currently underICU care • + One of : • Ventilator dependent, • Requires renal replacement therapy • INR > 2.0
LIVER SUPPORT SYSTEMS • Features – • Free passage of toxins requiring breakdown • Free passage of newly synthesized proteins • Exclusion of the patient’s antibodies/complement components to prevent cytotoxic effects • Prevention of cells in the support system entering the patient’s circulation
Concentration gradient Pressure gradient & Fluid flow
• Artificial Liver Support • Extracorporeal liver assist – No biological materials(hepatocytes/ cell lines) • Bio-Artificial Liver Support • Ideally – Human Hepatocytes; • Currently used - human hepatoblastoma cell • line HepG2/C3A; primary hepatocytes from pig livers.
Plasma exchange/Hemodiafiltrn PE – exchange non cellular components from blood with FFPs HDF – Washes plasma in dialysate to detoxify Molecular Adsorbent Recirculating System(MARS) Albumin dialysis within 3 circuit system 70 kDa pore size membr Charcoal filter, resin binding column Albumin doesn’t pass Fractionated Plasma Separation & Absorption(Prometheus) Larger porosity membr – 200kDa; toxin-albumin complex passes the membrane – alb purified ELAD(Extracorporeal Liver Assist Device) HepG2/C3A cells Hemoperfusion from patient through columns containing C3A cells Has 2 acellular membranes – to prevent hepatoblastoma cell spill into patient blood HepatAssist 70g cryopreserved porcine hepatocytes Plasmapheresis activated charcoal  Oxygenation  Hepatocyte bioreactor
• Drawbacks of ALS • No specific drawbacks • FULMAR Trial – RCT on MARS in ALF - no statistical significance in 6-mth & 1 yr OS • RELIEF Trial – RCT – MARS on ACLF – No significant survival benefit • MARS – No increased incidence of adverse events • HELIOS study – Prometheus in Acute decompensation in cirrhotic pts – No survival benefits – but subgroup analysis – MELD> 30 & HRS –type I – survival advantage • Drawbacks of BALS • Hep G2/C3A Migration into patient circulation(ELAD) • Zoonotic infections eg. Porcine Endogenous RetroVirus (PERV) • Isolated Primary hepatocytes(IPH) – lose function, undergo apoptosis under ex-vivo conditions ? • In 3D clusers, IPH don’t lose functions
ISCHEMIC HEPATITIS • Shock liver/ Hypoxic liver injury • Hypoperfusion/systemic hypoxemia  extensive hepatocyte necrosis • Transient massive rise - serum aminotransferases, rapid decline after oxygen supply restored. • 79% - predisposing acute cardiac event; 23% - sepsis • Passive congestion of liver  elevated R- sided pressures increase sinusoidal pressure impedes flow from PV • Trauma; Hemorrhage; Sepsis; Acute cardiac Injury(Myocardial stunning) • Sepsis – reduce oxygen extraction, increase hepatocellular O2 use • Rx – improve hepatic perfusion by increasing intravascular volume/ Inotropes
HEPATIC TRAUMA
• Not precise enough to predict the requirement of intervention • A, B, C  additional injuries; monitoring response to resuscitation • Deciding factors - mechanism of injury(Blunt v/s Penetrating), hemodynamic instability(+/-), response to resuscitation • FAST – • Rapid imaging in hemodynamically stable/ unstable patients with possible hepatic injuries • 4 views of abdomen - cardiac (for pericardial effusion), R& L upper quadrants, suprapubic (presence of fluid). • Sn – 83%; Sp – 99% • FAST for blunt abdominal trauma with hypotension – Sn & Sp may increase to 100%. • HD unstable FAST - + No Extraperitoneal source/ Exploration Hemoperitoneum suspect Rpt FAST/DPL Stil –ve, but still hemopritoneum suspect Diag/Therapeutic exploration
• CECT abdomen, pelvis – Most Sn, Sp imaging in Hepatobiliary trauma • If HD stable • Parenchymal lacerations/intrahepatic/ subcapsular hematoma +/- active extravasation of intravenous contrast • If CT worrisome for active IV contrast extravasation  repeated  active bleeding on venous phase • NOM – MC in blunt trauma pts - . 73% - NOM, with 7% - failure rate. • HD unstable/fail to respond to resuscitation/ hollow viscus injuries/peritonitis on exam  exploration • Grades I, II, III • Observe – Hb every 8 hrs for 24 hrs • Hb stable, diet Unstable/Transfusion+ • Discharge ICU/addl imaging/Sx
• AAST Grade IV/V • SICU/Hb 6hrly for 24 hrs(NOM) • Need for BT/HD instability Successful • Repeat CT/Angioembolizn/Sx Interval CT • Bleeding parenchymal injuries - best managed by vessel ligation. • Direct suture ligation - preferable to Surgical clips • Penetrating liver trauma + uncontrolled hemorrhage Options – • Balloon occlusion of tract/Tractotomy/Angioembolizn after packing • Hepatorrhaphy – for venous bleed/Bile leak • Non absorbable suture, horiz. Mattress – to ctrl small bleeding cracks(after ctrl of major vessels & ducts)
• Omental flap indications • Bleeding crevasses/post resection coverage of remaining surface/For larger area without liver capsule/Ruptured/surgically entered subcapsular hematoma with bleed
Principles of Hepatic packing Choose the appropriate patient Control arterial bleeding by Sx / angioembolization Lesser venous bleeding/coagulopathy - Packing Timing - before excess bleeding/ coagulopathy develops Beware of acute traumatic coagulopathy Pack to compress liver in superior to inferior plane Anteroposterior packing – compresses IVC Count sponges when feasible - facilitates later removal Temporary abdominal closure - avoids tension/ secondary abdominal compartment syndrome Operative Techniques for Control of Liver Injury Cautery Argon beam coagulation Hemostatic adjuncts Individual vessel ligation Parenchymal reapproximation with large mattress sutures (Hepatorrhaphy) Selective hepatic artery ligation(SHAL) Resectional débridement Hepatic lobectomy (or major resection Omental packing Packing and planned reoperation
Major HVI confined to liver parenchyma Sututre Ligation Bleed not readily apparent, collecting in deep crevasse Finger #, Tractotomy, localize  suture Avulsion of HV from VC Pack Fine vascular clamps to reapproximate anterior wall of VC & major HVs fenestrated endovascular stent grafts Historically – Cavo-Atrial shunting – ICD tube/ET tube through R atrium to IVC THVE – Pringle Suprehepatic Intrathoracic VC Suprarenal Infrahepatic VC DCS Perihepatic packing Avoid fascial closure(Prevent ACS) wait – 6 – 24 hrs Adjuncts of NOM Arterial blush Angioembolisation Hemobilia Angioembolisation Bile leaks ERCP, Sphincterotomy, stent Perihepatic collections Pigtail Large amt blood/bile/ascites  ACS D-lap (gasless system)  evacuation of major collections
Special PROBLEMS IN LIVER INJURY • S.C HEMATOMA • Less likely delayed bleed than splenic S.C.H • Indication of intervention – rupture(Temporary packing/Omental flap); contd expansion/assctd arterial blush(Angioembolisation) • HEMOBILIA • Blunt liver trauma days to weeks  Melena, jaundice(clinical/subclinical) • IOC – Arteriography(CTA) TOC – Angioemb. • BILHEMIA – Fistula btw IHBR to Vein • Bile Blood – Jaundice • TOC – Angioemb +ERCP/Stenting • LIVER AVULSION • Venovenous bypass  Autotransplant of liver • GB INJURY  TOC - Cholecystectomy
Aberrant HA angioembolizn
SIMPLE HEPATIC CYSTS • Origin – biliary tree – Microhamartomas/ peribiliary glands isolated from biliary ducts • Lining - Simple cuboidal epithelium • Contents – MC serous/ proteinaceous material from previous hemorrhage • Mucinous/ solid - implies infectious or neoplastic process. • MC in age > 40 yrs; F>M (some studies) • Symptoms –due to mass effect, liver capsule stretch; more in elderly • LFTs - N • USG – btw cyst/solid; Anechoic masses/smooth margins/thin walls/ Lack of septations • CT - nonenhancing/water density (0-10 U)/ smooth,thin walls – drawback – small lesions not characterized • MRI – Imaging of choice for newly discovered liver lesions; smaller lesions; homogenous hypoT1, hyperT2/Non-enhancing – Hemorrhage – hyper T1,T2; fluid-fluid level
SIMPLE HEPATIC CYST • INTERVENTION – Symptoms/suspicion • Aspiration – 100% recurrence • Aspiration & sclerosant injection (if no bilious communication)– 20 – 80% recurrence • Cyst fenestration – lap/open – 1st aspirate – if bilious – look for communication – oversew • Lap v/s open – recurrence/morbidity - <10% • Resection – least recurrence, max morbidity • TOC – Lap fenestration – min morbidity, comparable recurrence
POLYCYSTIC LIVER D/S • ADPKD/ADPLD • ADPKD – PKD1, PKD2 gene mutations ; ADPKD – predicts size of renal cysts, not liver • ADPLD – SEC63, PRKCSH genes • Prevalence – F>M, increases with age, exposure to pregnancy, hormonal Rx • Symptoms – mass effect, capsule stretch • Complications – 5% - cyst infection, PHT, ascites, variceal bleed, HVOO • Gigot et al classfn of PLD – CT scan based – guides Rx • Type 1: </= 10 cysts >10 cm/large uninvolved liver parenchyma. • Type 2: Diffuse liver involvement/ medium- sized cysts/large uninvolved liver parenchyma. • Type 3: Massive, diffuse liver involvement/ a few areas of normal liver parenchyma.
POLYCYSTIC LIVER D/S • TREATMENT - if reduces hepatomegaly/long term relief • Medical – Immunotherapy – sirolimus/Somatostatin analogues – studies – palliative • Percut Transcatheter Hep A embolization - palliative • Aspiration & sclerosant – 30-100% recurrence • Sx – Fenestration(for type 1)MC complication – Ascites)/resection/LTx(for type 3- NO SURVIVAL ADVANTAGE).
HYDATID DISEASE • E. granulosus (worldwide; unilocular, spherical)/multilocularis (metastatic d/s)/oligarthrus(peripheral ie skeletal muscles)/vogeli • Dvptl stages: adult tapeworm (sexual stage), cystic/ infiltrative larval metacestode (asexual) • Adult tapeworm – head/scolex, body/strobila, with three or four proglottids –The last proglottid - largest -have mature eggs - eggs have embryo/oncophere/hexcanth -3 pairs hooklets. • Cyst expansion – slow - < 1 cm diameter per year • Symptoms are unusual until cysts reach 10 cm
HYDATID DISEASE • 3 layers: Germinal layer/Laminated layer/Advential layer. The • Central hydatid cavity with fluid Germinal – layer(Germinative membrane/living part)  Laminated layer. • Germinal + Laminated layers = Endocyst • Ectocyst/pericyst - fibrous layer(Compression of host tissue around endocyst). • Germinative layer - produces protoscolices
HYDATID DISEASE • Adult tapeworm – in dog(MC definitive host) intestine – releases infected EGGS  dog feces soil/water/plants intermediate host, sheep (humans - accidental intermediate hosts) eggs hatch, embryo migrates through intestinal wall portal system. • Metacestodes (larval forms) - liver, lung, spleen, kidney, brain, bone – hydatid cyst with proctoscolices – ingested by dog • 80%- single organ involved.
HYDATID DISEASE • Brood capsules – Invaginations into cyst cavity by undifferentiated cells in germinal layer – contain numerous proctoscolices • Germinal layer – secretes fluid/source of daughter cysts • Daughter cysts lack - adventitial layer . • Daughter cyst formation – by endogenous (MC)/exogenous vesiculation (leak in laminated layer – ‘satellite’ daughter cyst – 16-65%) • Ectocyst/Pericyst – host response - present in – liver, spleen; absent in – lung, brain • Uncomplicated cysts – sterile hydatid fluid • Bile-stained cyst fluid - cystobiliary communication. • Superadded infection – purulent fluid • Degenerated cyst – turbid fluid • MC site of liver involvement – R lobe; seg VII/VIII
HYDATID DISEASE • COMPLICATIONS : • COMPRESSION – Compensatory HT(Adj liver); OJ(Bile duct); Budd Chiari – like(IVC/HV); Sinistral HT(Splenic V) • INFECTION – bacteremia/biiary communication • RUPTURE – 1. Bilary tract 2. Bronchial tree 3. Peritoneum 4. Other organs • Cysto-biliary communication(CBC) – MC complication • Minor(size < 5mm – reveal postop – bile leak); Major (5-10% incidence, size > 5mm)– OJ/Cholangitis • Incidence – symptomatic - 1 – 42%; total - 90% • Cyst size > 10 cm/near hilum/high pre-op GGT – high risk factors predictive of CBC • Major CBC – daughter cysts slip into biliary system (65%) – cholangitis; less in minor CBC • Diagnosis – US/CT – detached membranes, IHBRD/EHBRD; ERCP - Confirm obstruction • Rx – ERCP; sphincterotomy, extraction of debris with balloon
HYDATID CYST D/S • BRONCHIAL RUPTURE (BBF) - Rare – MC in cysts in posterior, upper segments of the liver (IVa, VII, and VIII) • INTRAPERITONEAL RUPTURE – secondary hydatidosis; Spontaneous/trauma – 1-8% - silent/symptomatic/ acute abdomen +/-; anaphylaxis – 1% • Incidence of primary peritoneal hydatidosis – 2% • < 5 cm – usually asymptomatic • Abdominal pain; cholangitis; anaphylaxis(intraperitoneal rupture); bronchobiliary fistula • DIAGNOSIS – • Increased ALP, GGT – CBF • Increased TLC – infected cyst; Eosinophils > 3% - in 25-45% of pts • Serology – confirmatory - for D/D, Post Rx F/U, Epidemiological surveillance – MC used – Ab detection – IEP, Blotting, ELISA • False +ve – other helminth infn; low +vity in children • ELISA – Sn – 85-98% - IgM - -ve after 6 months of successful Rx; IgG - +ve for 4 yrs
• RADIOLOGY – • CT and MRI - indications – • Subdiaphragmatic location • Disseminated disease • Extraabdominal location • Complicated cysts (abscess, CBF) • Presurgical evaluation. • MRI > CT – For characterization of lesion; higher Sn • US - first-line imaging -at both individual & population levels • WHO Classification, GHARBI Classification
HYDATID CYST DISEASE – WHO CLASSIFICATION - USG Cyst type WHO Classification GHARBI Description CL (D/D needed) well-circumscribed liquid image with clearly defined wall – Early stage active, fertile cysts CE1 I Concentric hyperechoic halo around cyst; hydatid sand + – free floating active, fertile cysts CE2 III Multivesicular; daughter cysts; Rosette/honeycomb/spoked wheel/cluster active, fertile cysts CE3a, CE3b II Laminated layer detaches; undulating membranes; Water lilly/ water snake transitional, active or inactive cysts CE4 IV Solid & Liquid components; no daughter cysts Degenerated, inactive CE5 (Least typical of hydatid; D/D needed) V Amorphous mass; solid/ semisolid components; calcification in pericyst Partially/ totally calcified
• CT/MRI - indications • If Sx Rx planned • subdiaphragmatic location • disseminated disease • extraabdominal location • Cysts close to hilum • Complicated cysts (abscess, cystobiliary fistulae) suspected • T2-weighted MRI - low signal intensity rim - characteristic sign of hydatic disease • Daughter cysts – T1 – hypo; T2 – hyper re;ative to cyst fld • MRI + MRCP - preoperative diagnosis of cystbiliary fistula (80% Sn, 100% Sp) • Intracystic fat density in MR – CBC
HYDATID CYST TREAMENT • Goals – • Entire parasite removal • Residual cavity removal • Identification, treatment of biliary fistula • Modalities - • Radical surgery • Conservative Sx • PAIR • Benzimidazoles (BMZs)
HYDATID CYST TREATMENT Modality Indications Contraindications Medical < 5 cm CE1, CE3a Peritoneal cysts Multiple cysts in > 2 organs Prevent recurrence following surgery or PAIR Pregnancy Uncomplicated CE4 and CE5 Alone if cyst > 10 cm Cysts at risk of rupture Chronic hepatic disease Bone marrow depression PAIR >5 cm; CE1, CE3a Inoperable/Refusal/Relapse/Failure to respond to Rx Biliary fistulae CE2 CE3b CE4 CE5 Surgery Large CE2-CE3b cysts with multiple daughter vesicles Single superficial liver cysts Complicated cysts(CBC, Infn, compression) General contraindications for surgery Uncomplicated CE4 and CE5 Very small cysts
Sx • Avoid spillage; protection of peritoneal tissue & organs - protoscolicide-soaked surgical drapes, soft injection • Protoscolicides - 70% - 95% ethanol, 15% - 20% HTS, 0.5% cetrimide • At present - 20% HTS - recommended • Contact germinal layer - >/= 5 min; • Avoid in CBC – Chemical sclerosing cholangitis • Periop Albendazole(ABZ) – 1 day before – 3 mnths after Sx • Thoraco-abdominal incision only when simultaneous R lung & liver d/s – combined Sx • Lap v/s open – Chinese literature – results comparable; MC performed lap procedure – Cystectomy
Conservative Sx • Cystectomy/ closed cystectomy/ cyst unroofing – simple, safe than radical Sx • No liver resection; • Risk – spillage, secondary hydatidosis – Highest in cystectomy • Steps – 2 layered packing – NS, HTS  punction aspiration injection (if no CBC) hydatidectomy (daughter cysts, laminated, germinal layers) unroofing (adventitia layer and thinned-out liver). • Min contact time with proctoscolicide (20% HTS) – 6 min) – Risk - Hypernatremia • CBC – IO Cholangiogram/GB compression/Transcystic methylene blue • Rx – MC – Suturing> RYHJ, Liver resection • Residual cavity – MC – Omentoplasty + DT; Capitonnage, capsulorrhaphy – not used • Post-op complications – • Biliary fistula (1-10%) – Sphincterotomy/ENBD/Combinations – 85- 100% success – closure in 2-4 wks • Biliary stricture  secondary cirrhosis – Sx not feasible – Long term endoscopic stenting safe
Radical Surgery • Pericystectomy - radical cystectomy/capsulectomy/total pericystectomy/cystopericystectomy/pericyst ectomy –complete removal of the hydatid cyst. • Sx plane – just outside pericyst layer without opening the cyst • Plane – no difference from that of classical • Contraindication - cyst impinging on Hepatic V, IVC, liver hilum. • Liver resection – • The only surgical Rx for E. multilocularis; but too radical for E. granulosus • Other rare indications – • Atrophic remnant liver parenchyma, • Large bile leak untreatable Roux loop. • Peripherally placed cysts in left lateral segment • Pedunculated lesions
• Recurrence – incidence – 10% • Predictive factors – Lap approach; cysts> 7 cm • H/O liver hydatid cysts, number of liver cysts, surgeon’s degree of practice • Close F/U @ 6 month intervals • +ve serological test during F/U – not s/o recurrence; Rising titre – s/o
• PAIR – destruction of germinal layer • PAIR Catheterization - evacuation of enrire endocyst • PEVAC - percutaneous evacuation of cyst content • Risk - spillage of hydatid fluid during puncture • Prevention - US/ CT guidance, transhepatic approach to the cyst approach, • PAIR – Ben Amor et al. – • Indications for PAIR + MBZ/ABZ(Pre & post procedure) - large (>5 cm) CE1 & CE3a cysts. • Interval between injection of proctoscolicidal agent and Reaspiration – 15 min • Signs of involution - 3 mths heterogeneous reflections of cyst content 5 mths obliteration and pseudotumor appearance 9 mths loss of echogenicity, cyst disappearance
• PAIR Catheterization – Akhan et al – • PAIR followed by catheter – iin situ for 24 hrs – if no Bile stain  cystogram to confirm • < 10 ml bile for 24 hrs – absolute alcohol injected (25-35% of cavity volume) 20 min  aspirate  withdraw catheter • > 10 ml bile for 24 hrs – catheter left in situ – till < 10 ml • PEVAC(Percut evac of cyst content) – Saremi, McNamara et al – • Aspiration  catheter left in situ  catheter replaced with 14 -18 Fr stiff sheath  suction catheter into cavity  cyst contents – evacuated by suction  Special cutting instrument - to fragment & evacuate daughter cysts, laminated membrane – Simultaneous scolicide irrigation • Catheter left in situ – remove > 24 hrs > 6 cm OR volume > 100 ml PAIR Catheterization < 6 cm OR volume < 100 ml PAIR
• Benzimidazoles – MBZ & ABZ – • Kill by impairing glucose intake • ABZ better – better absorption in GIT, better results • 10 mg/kg BD with meals – NOT with antacid/H2 blockers/PPI • Alopecia – completely reversible; side effects – 1-10% • Single cysts – Rx Duration - 3 - 6 months. • Most relapses – within 2 yrs after treatment – but can occur 2 - 8 yrs • Efficacy of preoperative ABZ treatment – • Pre-op ABZ - 1 week before surgery. • Post-op treatment – 3 – 8 wks if no spillage; 3 -6 mths if spillage • ABZ - 10 - 15 mg/kg/day 2 doses • Fat rich meals - increase bioavailability. • Contiuous – No monthly treatment interruption • MBZ - 40 to 50 mg/kg/day, in 3 divided doses with fat rich meals
• WAIT & WATCH - • Uncomplicated cysts (types CE4/ CE5). • CL cysts - not treated until diagnosis certain • ALVEOLAR ECHINOCOCCOSIS - • Metacestodes of E. multilocularis – infective form • Definitive & intermediate hosts – wild animals - exclusively in the liver - does not form cysts • Primary extrahepatic locations – rare • Infiltration/ metastasis – from liver to other organs
ALVEOLAR ECHINOCOCCOSIS • Treatment • Radical surgery (R0 resection) - first choice if suitable • ABZ - mandatory in all - temporarily after complete resection of the lesions; for life - in all other cases; and (3) • Interventional procedures - preferred to palliative Sx.
LIVER ABSCESS - PLA • ETIO-PATHOGENESIS • MC – Ascending biliary infection due to obstruction – East – stones; West – malignancy (cholangioCa) • GIT • Hematogenous spread – endocarditis, IV drug abuse • Trauma, TACE – necrosis – Secondary infn • BEA stricture – infn • Cryptogenic – 25% • Predisposing – DM, Cirrhosis • Presentation – initially non sp. Prodrome  later localize – RUQ pain, fever/chills, malaise(Triad); • MC symptom – Fever> RUQ pain • DIAGNOSIS – • Lab – TLC increase, Hypoalbuminemia, increased liver enzymes – Non specific • Radiology – • Chest X-Ray – elevated R hemidiaphragm/air- fld level in subdiaphragm. area, Pleural eff; Atelectasis – 50%
LIVER ABSCESS - PLA • USG – Initial IOC – Sn – 83 – 95% • Assesses maturity of abscess – Hyperechoic, indistinct initially hypoechoic, distinct walled • IHBR, Hepatolithiasis, CBD calculi • CECT Abdomen – PLA v/s other liver lesions • Sn – 93-100% • Smallest size of liver abscesses detected – 0.5 cm • Micro v/s Macroabscess - < 2cm v/s > 2 cm
LIVER ABSCESS - PLA • Microabscesses – Miliary v/s Clustered • PV phase - peripheral rim enhancement(hypodense cystic lesion + segmental wall enhancement, surrounding low-density edema) • Narrow Transition zone btw hypodensity & peripheral rim • MR – No sp. Advantage compd to CT • Indication – Diagnostic uncertainty even after CT abdomen • T1 – hypo, T2 – Hyper; MRCP – level of obstrn
LIVER ABSCESS - PLA • MICROBIOLOGY • Pathogen isolation – Cavity > blood C/s • 33-55% of abscess cavity C/S – polymicrobial; less frequency of blood C/S polymicrobial • GP, GN, Anerobes • MC – E. coli, Strep,Enterococcus, Kleb • K. pneumoniae- (Asia> West) – Invasive K. pneumoniae liver abscess syndrome – Lungs, CNS, Eyes • K. pneumoniae in this – addl virulence factors – Capsular type K1, K2 Ag, magA, rmpA • MC isolated anerobes – Bacteroides> Strep milleri • Hematogenous spread – Staph aureus, Strep sp. – Solitary • GI spread – Polymicrobial, Aerobic GN, GNAnerobic • Gm staining – Sn Sp Gram + cocci 90 100 Gram –ve bacilli 52 94
LIVER ABSCESS - PLA • TREATMENT – • ABs • Blood C/S, Abscess cavity aspirate C/S • Initially Broad spectrum AB • Biliary disorders - GNB, Pyeliphlebitis - GN & Anerobic • Extended-spectrum penicillins (piperacillin- tazobactam, ticarcillin-clavulanate, ampi- sulbactam), carbapenems, or 2nd gen ceph +/- metro • Started parenterally for 2 - 3 wks  convt to oral - complete 4-6-week course • DRAINAGE PROCEDURES - • PCA, PCD – Mainstay of Rx for PLA(1st line) • Multiple PCD/ multiple aspirations – effective • Rx underlying cause – MC – biliary obstruction/ communication • Predictors of failure of PCD - • Abscess C/S – yeast; Abscess cavity – biliary communication • If PCA/ PCD fails – Sx drainage/ liver resection
LIVER ABSCESS - PLA • ENDOSCOPIC PROCEDURES – • EUS guided TG/TD plastic/metal stent/ catheter drainage • For PLA with communication with IHBD  ES + Nasobiliary drainage/ stent – removed > 4-6 wks • Median time for fistula closure – 6 days • LAP Rx of PLA & ASSCTD PATHOLOGY - Indicns • Failure of medical Rx & PCD • C.I to PCD • Septic shock needing emergency Sx • Surgically accessible lesion, minimal vasculobiliary injury risk • No previous major Sx in RUQ • No concomitant conditions requiring additional surgery • Shorter time to oral intake, LOS - in laparoscopic group (P <.05). • Video – Assisted Hepatic Abscess Drainage, VARD.
LIVER ABSCESS -PLA • SURGICAL DRAINAGE • INDICATION • Failure of medical management • Failure of PCD • Complications secondary to PC treatments(bleeding/ spillage) of pus into the peritoneal cavity • Exploration - control of any associated intraabdominal pathology is performed. Localization of all abscesses (palpation liver & IOUS). • Needle aspiration to confirm location abscess & C/S & Gram stain. • The area of abscess isolated from abdomen with laparotomy sponges. • Suction  Suction drainage
LIVER ABSCESS - PLA • HEPATIC RESECTION • Single/ multiple PLA is with severe hepatic destruction partial hepatectomy – best therapeutic option • Low mortality rate • Underlying malignancies who require hepatectomy for liver destruction secondary to PLA poor outcomes • Worldwide – 3-30% • INCIDENCE OF MALIGNANCY IN PLA • Incidence of GI cancer was 4.3 times higher in patients with PLA • PLA pts - highest incidence of colorectal cancer > biliary tract > pancreas > small intestine
LIVER ABSCESS - ALA • E. hystolytica(invasive form) • Majority – asymptomatic • Liver – MC extraintestinal site – Hepatic abscess - 3-9% incidence in amebiasis • R/F – • Male (though intestinal amebiasis – M=F) – Alcohol/Menstruation/hormonal • 4th – 5th decade; Poor health & sanitation • Immunocompromised – HIV • LIFE CYCLE • Trophozoites – shortlived outside; Cysts – days – wks outside human body • Resistant to gastric pH, excystation in alk pH – R colon (MC affected intestinal amebiasis) – PV radicle – R lobe liver • Anchovy paste – sterile usually – dead PMN + dead hepatocytes • IMMUNOPATHOLOGY – • Early stage – PMN surrounding trophozoites • Later – 3 days – Lymphocytes, Macrophages, Epithiloid cells – Granuloma formn
• CLINICAL PRESENTATION • Amebiasis – MC asymptomatic • ALA MC symptom – High grade Fever, RUQ pain/ ?previous dysentery • Pleuritic & right scapular pain - if the diaphragmatic surface of the liver – involved • Young males - tender, solitary, R-lobe abscess. • Amebic serology titers > 1 : 256 IU • Jaundice – uncommon – Compression >> fistulization • LAB INVESTIGATIONS • Amebiasis/ dysentery – First step – Feces Light MS • Trophozoites in feces/submucosal biopsies • 3 stool specimen – different days over 10 days • Charcot leyden crystals & blood - acute stage • Fecal occult blood • Diagnosis of ALA - confirmed by +ve serology Sn -> 94% & highly Sp >95%. • False neg – in 7th – 10th day • Ab detection - IHA, LA, CIE, • Amebic gel diffusion test, immunodiffusion, CFT, IFA, ELISA – ELISA MC
• Serology +vity – endemic v/s non endemic area (acute infn) • PCR – IOC for clinical/ epidemiologic studies – In West - feces, tissues, abscess aspirate. • IMAGING • CXR – 50% shows changes • USG – Hypoechoic well defined; round edges – 90% diagnostic accuracy; guided aspn • CT – Imaging study of choice – solid lesions D/D; Guided aspn • ALA V/S PLA – less clear • Radiological resolution – 3 – 9 mths to yrs • SITES – • Liver>> Brain(CT – irregular lesions – no capsule/enhancement) • Intestine – ameboma(mimic Colon Ca; GI bleed, Rectovag fistula) ALA PLA Sero titres Amebic sero> 1:256 < 1:256 Albumin Less severe Severe HypoAlbuminemia Liver enzyme(no value) Less elevated More elevated ALT, ALP
LA in children • PLA >> ALA(Rare) • Rx – Amebicides (Metronidazole); No indication for aspn if uncomplicated • Porraz Ramirez criteria – Per cut. Aspn of ALA • No clinical improvement • Abscess diameter > 6 cm • Sepsis • Imminent rupture • Sharma criteria – Both ALA & PLA – Indications for PCD Sx drainage Large volume, high risk rupture Failed PCD Rupture already happened Pts on steroids E/O Liver failure Addl mgmt. of underlying abdominal problem Lack of response to med Rx ascites
ALA - Rx • MEDICAL • Predictors • PCD, Sx Drainage • Indication for aspn • Age 55 years or • Old age, >/= 5 cm, Bilobar involvement, > 7 days Class Prototype dose Features Nitroimidazoles Metro 750 mg IV/oral TDS 7 – 10 d High tissue diffusion, cross abscess wall Dehydroemetine paromomycin,(DOC) diloxanide furoate; and iodoquinol
Rx of ALA Drug treatment Uncomplicated ALA Both amebic colitis and LA— nitroimidazole derivatives (e.g., metronidazole) Amebic colitis—luminal agents - paromomycin, diloxanide furoate, iodoquinol PCD Deterioration in clinical condition despite adequate treatment Sx Ruptured abscess Impending rupture Inadequate catheter drainage
• BILIARY COMMUNICATION – • OJ, Longer duration, larger abscess • ERCP Sphincterotomy – CBD Stent/ NBS • COMPLICATIONS • Rupture – into chest, abdomen • R/F – L lobe; 5-10 cm size • MC – peritoneum – 20-70% > pericarditis (30% mortality) • HV & IVC thrombosis. • Bacterial superinfection/ anemia/ARDS/sepsis • R/F for poor outcome for ALA • BR>3.5 mg/Dl • Encephalopathy • Hypoalbuminemia <2.0 g/dL • Multiple abscess cavities • Abscess volume> 500 mL/ anemia/ DM • Liver resection in LA • Infected hepatic malignant neoplasm, • Hepatolithiasis • Intrahepatic biliary stricture
Hemangioma • MC; 70% of solid benign liver Trs. • F:M = 5:1; Middle age • > 10 cm = Giant hemangioma • Mostly solitary; 40% Multiple(same lobe) • Compressible/capsule • Endothelial cells/fibrous septa - cavernous vasc. spaces lined endothelium by connective tissue • B.S - Hepatic A/lack biliary or portal structures. • Endothilium – Vasc. Diffntn; Not portal • MC asymptomatic; incidental – at Sx/imaging • Symptomatic - giant hemangiomas - abdominal pain. • Mass effects - size, early satiety/biliary stasis/vasc obstn. • Complication – Rupture/Inflammatory reaction/ Kasabach Meritt syndrome (Intravasc coagulation, clotting, fibrinolysis  systemic DIC Uncontrolled bleed - 30-40% mortality Reversible by Sx removal)
Hemangioma • Etiology – Congenital vasc. Malformn/Hamartoma – Growth is by Ectasia/ No e/o Hormonal etiology • Diagnosis – • USG – Hyperechoic/acoustic enhancement/Sharp margins; if large – heteroechoic • CEUS/CECT - rapid peripheral nodular enhancement (arterial phase) F/B centripetal filling • IOC – MRI – T1 hypo, T2 strong hyper/DWMRI – High apparent diffusion coefficient • Others – SPECT/Tc 99m scan/Hep Angiogram • Hepatic Angiogram - COTTONWOOL app. - large feeding vessel – displacement, pooling of IV contrast. • No Percut Bx – low yield/Risk of bleed • Treatment – Asymptomatic, estd diagnosis – No intervention • Indications for Intervention –Diagnosis uncertain/symptoms/inflammatory reaction/Kasabach-Merritt syndrome/rupture • Standard liver resection preferred to enucleation • LTx – Giant Hemangioma (difficult resection)/associated Glycogen storage d/s
HEMANGIOMA – T2, T1, A, PV, Delayed phases
Hemangioma • Medically Unfit for Sx/Technical reasons – Arterial embolization/ RT • Kasabach Meritt – Gold standard is resection – pre-op FFPs
FOCAL NODULAR HYPERPLASIA • 2nd MC Benign hepatic neoplasm; • F:M = 8:1 • usually < 5 cm, 80% - Solitary. Only 3% >10 cm • Macroscopy - Lacks a capsule • Central scar around arterial vessel with fibrous septa radiating outward. • Microscopy - Normal hepatocytes arranged in thickened plates. • Kupffer cells +, hepatocyte-derived • biliary ductules, nodules + • No bile ducts bile • MC asymptomatic, incidental diagnosis • If symptomatic – compression/torsion • Rupture – rare • Malignant transform – not documented • Etiology - hyperplastic, regenerative response to malformed arterial structures • Associations – hepatic hemangioma, hereditary hemorrhagic telangiectasia (Osler- Weber-Rendu disease) • Genes involved – deregulation of vascular remodeling • Female hormonals & OCPs – not proven
FOCAL NODULAR HYPERPLASIA • Pre-contrast – lesion - same US echogenicity/ CT attenuation/ MRI signal intensity as the surrounding liver tissue • Arterial phase - strong homogeneous enhancement with central vascular supply, & sparing of central scar • Portal,delayed phases – Contrast fades, lesion similar to surrounding liver • MRI – Precontrast – T1 – lesion – ISO/HYPO; • T2 – ISO/HYPER; Central scar – Strong HYPER • Superparamagnetic iron oxide (SPIO) contrast uptake – by Kupffer in FNH – differentiate from adenoma on MRI. • Scintigraphy with technetium 99m– sulfur colloid – Due to Kupffer • Angiography demonstrates a “spoked wheel appearance • Bx – in diagnostic uncertainty – low yield • Management – Asympt – No Rx/No stopping OCPs/Pregnancy • If sympt – resection – lap/open • Pedunculated lesions – Risk of torsion - Sx
HCA • Rarer type • Young women - childbearing age • long-term - OCPs - 30-fold HCA increase • Newer low-dose estrogen +/- progesterone formulations- reduction in HCA • Multiple adenomas – in 30% pts • Adenomatosis – Multiple HCAs in all liver segments – No relation to hormones; associated with Glycogen storage d/s (Type Ia glycogenosis) • Types of HCA – Inflammatory(Telangiectatic)vHNF-1A mutn, Beta Catenin mutn; Unclassified • MACRPSCOPIC – Well circumscribed; pseudocapsule; C.S – Heterogenous, yellow brown, H’ge, necrosis
• MICROSCOPY – Hepatocyte cords sepd by sinusoids; No KC or ductules • PRESENTATION – MC – Asympt, incidental; MC symptom – Abd. Pain; 1/3rd of IHCA pts – inflammatory syndrome + fever • MC Complication – bleed – 25% - sudden pain, shock; > Malignant transform(4-5% risk) • ETIOLOGY – Hormonal – OCPs(Dose dependent),pregnancy enlargement; androgen preparations, illicit androgen use by bodybuilders, NASH, GSD I, III, Obesity/metabolic syndrome R/F for bleed R/F for malignancy large tumors (>5 cm) Large Trs > 5 cm lesional arteries male gender (6- to 10-fold increased risk) IHCA subtype Beta catenin subtype L Lateral location of Tr Androgen use Exophytic growth
• RADIOLOGY • USG - variable echogenicity; often hyperechoic (high lipid content) • Internal hemorrhage - cystic areas, +/- calcification • Intratumoral veins - on Doppler • CEUS arterial phase, - diffuse/ centripetal hypervascular enhancement from dysmorphic arteries. • PV phase -showing equal enhancement/soft washout relative to the liver • CECT Abdomen – • Appearance overlaps with FNH & HCC. • Plain CT - Similar attenuation to normal liver • A phase – • homogeneous enhancement, sharply marginated hypervascularity • Capsulated appearance(30%) • PV phase – fade. • Larger adenomas - more heterogeneous than smaller lesion(Hemorrhage)
MR IMAGING FEATURES – HCA Type of HCA T1 T2 A PHASE Dynamic phase Delayed HB phase Inflammatory (30- 50%) Sn-87-91; Sp- 91-100 Hypo Strong Hyper – diffuse/rim- like(atoll sign) Moderate enhance Persistent enhance Variable uptake HNF – 1A(30-35%) Exclusive women Sn- 85-88%, Sp-88- 100%) Slightly hyper (Homogenous) Iso/hypo (varying) Less avid enhance than inflammatory Low uptake Homogenous low uptake Beta Catenin type(10-15%) – GSD, Androgen, male – almost HCC like Hypo/hetero Hyper/hetero Moderate/hetero enhance variable variable Unclassified (10%) – Almost HCC like No specific imaging characteristics
IHCA – Plain T2, A, Delayed V
HNF-1A HCA – T2; T1, A, PV, Delayed
TREATMENT OF HCA • HCA • Male Female • • Resect < 5 cm > 5 cm • HNF1A Others • F/U Resect • F/U – 5 yrs > cessation of HRT/OCPs – Annual MR(Non IHCA)/ Bi-annual MR(IHCA subtype) • LTx – sympt. Unresectable HCA/ Adenomatosis/assctd GSD • Risk of complicns in adenomatosis(mostly HNF-1A type) v/s solitary adenoma – same • HCC< 5 cm with no bleeding – no need to discourage pregnancy
Benign Hepatic Neoplasms Prevalence 3 – 20% HEMANGIOMA 1% FNH < 0.05% HCA Pathogenesis Vascular malforn/Hamartoma - congenital Hereditary; Hyperplastic response to vasc. malformn Sex Hormones/NASH/Glycogen storage d/s I, III AFP Normal Normal Normal Gross appearance Compressible/well ademarcated/Pseudocapsule (blood-filled “cyst”) No capsule/Brown, lobulated/central scar Pseudocapsule/ yellow-brown lipid/H’ge/Necrosis/Calcifn Microscopy Cavernous vascular spaces/endothelial lining/no bilio- portal str. Normal hepatocytes in thick plates/Kupffer cells, hepatocyte- derived biliary ductules – no bile duct Lipid/Gycogen rich Hepatocytes in plates; sepd. By sinusoids – Arterial perfusion Complications Mass effect, inflammatory reaction, Kasabach- Merritt syndrome Mass effecr/torsion if pedunculated Malignant Transformation N N Y, Male/Androgen/b-HCA, Tr diameter > 5 cm Rx Sx if sympt - enucleation/resect; Unresectable – LTx/embolisation Sx if sympt/Pedunculated; Hormonal Rx cessation – Not needed Sx – size, gender, subtype Hormonal Rx cessation - needed
• Angiomyolipomas - mesenchymal tumors from perivascular epithelioid cells • MC in kidey; also appear in liver • Associated with tuberous sclerosis • MC in women between 30 and 50 years of age. • MC – asymptomatic, incidental diagnosis – less accurate • Inconsistent appearance(varying content - smooth muscle cells, adipose tissue, and blood vessels) • Liver biopsy often needed • Asympt, size < 5 cm  Surveillance with serial imaging • Size > 5cm – resect(Malignant transform risk) • IPL(Infl. Pseudotumor of Liver) • Benign, mimic cholangio Ca • Fibroblastic proliferation with PMN infiltration • Fever, abd. Pain, LOW, Jaundice • Imaging – challenging diagnosis • D/D – Cholangio Ca/AI cholangiopathy/ PSC
• BILIARY HAMARTOMA (von Meyenburg complex) • Benign tumors – with disorganized bile ducts, ductules with fibrocollagenous stroma • Size - range from 1 to 15 mm; no biliary tree communication • Scattered throughout the liver • MC multiple, may be solitary • Nonspecific imaging appearance • T2-weighted MR images - multiple small strongly hyperintense lesions • D/D – cysts/metastases or microabscesses • No treatment needed • PELIOSIS • Multiple small blood filled pools in liver parenchyma – various sizes • Due to focal rupture of sinusoidal walls • Post Oxaliplatin chemo for CRLM; Anabolic steroids, OCPs, HIV, severe TB • Strong hyper T2-weighted MRI, anarterial phase enhancement in CT/MR • Usually – asymptomatic – rarely – rupture, bleed • Rx – withdrawal of causative agent
• NODULAR REGENERATIVE HYPERPLASIA • Benign, diffuse, micronodular transformation of liver with hyperplastic hepatocytes • Primary vascular process  PV obliteration  ischemia, central zone hepatocyte atrophy proliferation of hepatocytes • Preneoplastic theory (Assctd HCC, Neoplasia) • 2% prevalence • Assctd with systemic d/s, drugs, steroids • Incidence in oxaliplatin-based chemotherapy for CRLM - 24% • Usu. Asymptomatic, clinically preserved Liver fn; occasionally PHT features – bleed • APRI score – AST: Plt Ratio Index >0.36, Plt < 1 L in CRLM chemotherapy pts – predictive of NRH • MR – T1 – hyper; T2 – Iso/hypo to liver • No central scarring • If imaging –ve PC Needle Open Bx • Rx – Asympt – No Rx; In Oxaliplatin chemo for CRLM, Bevacizumab reduces NRH incidence • Manage PHT • If NRH +  Avoid major resection OR do PVE
• MC liver d/s assctd with FNH Like Lesions – • BCS • HHT • Congenital Hepatic Fibrosis • PV Cavernomatous transform
HCC • R/F • VIRAL – HBV/HCV • Heavy alcohol, smoking – Independent & synergistic • Aflatoxin B1 • T2DM – increase risk in HCV pts • Coffee intake reduces risk • Cirrhosis underlies HCC in - 90% of cases • MCC of death in Cirrhotics - HCC • NAFLD/NASH - increased risk • GENETIC INFLUENCE IN HCC • Chronic hepatitis  Persistent inflammation HCC • Maintained injury --> repair with high proliferation rate  increase DNA mutn • HBV – Genetic damage by – inflammation + integration (genetic &epigenetic) into host DNA • HBV – Genetic damage –even without much liver insult –(cirrhosis) • HCV – Chronic inflammation
FLHCC • Well demarcated, encapsulated, +/- central fibrotic area • Longterm survival – 50-75%; recurrence – 80% • Lymph node mets – worse outcome • LN mets & mets – Rx – resection • Gain in Protein kinase A activity – genetic basis for FLHCC • nonelevated AFP with large tumor, normal liver. • Plasma neurotensin levels, vit B12 binding capacity - increased
PATHOLOGICAL VARIANTS OF HCC Mixed Hepatocellular-Cholangiocellular Tr Prognosis – better than HCC, worse than IHCC Clear cell HCC Resemble RCC Better prognosis than std HCC – controversial Pleiomorphic/Giant Cell Variant Origin – primary hepatic cells Sarcomatoid HCC/Carcino-Sarcoma Higher incidence of mets; No AFP Childhood HCC 25% of pediatric liver tumors Rare in infancy Viral Hepatitis, metabolic causes of liver cirrhosis Longterm survival 10-20% -higher multifocal, vasc. Invasion, extrahepatic mets Resection
• Preventable R/F – • Preventn of viral infn – Vaccn HBV, Prevent blood transmissn of HCV • Alcohol intake • Aflatoxin contaminatn • Obesity  NASH • Decrease in viral replication  reduce HCC incidence • Antiviral therapy – SVR in HCV pts  cirrhosis/fibrosis regression • SVR  Reduced HCC risk • SCREENING FOR HCC • Abdominal US 6 mthly for cirrhotics – if HCC in them is treatable • AFP – NOT RECOMMENDED – Suboptimal accuracy - cholangiocarcinoma, Ca stomach, Liver mets – may produce AFP • Contraindication – LTx candidates with advanced liver d/s < 1 cm, Cirrhotic Not Malignancy in 60% Close F/U > 1 cm, Cirrhotic Characteristic AHE + Venous washout Single imaging enough to diagnose HCC No AHE + Washout FN Bx
• Preop biopsy – not reqd for diagnosis – Risk of Tumor spillage(1%), H’ge • Mets – MC – Lung, bone, peritoneum • Chest CT – Mandatory, bone scan – only if symptoms • Staging Lap – indications – • Clinically apparent cirrhosis • Radiologic evidence of vascular invasion • Bilobar tumors • STAGING SYSTEMS – • CUPI – Population specific system • CLIP • Okuda
• Non-Cirrhotic liver – Diagnosis of lesion of any size – by Histology • PIVKA, Glypican 3, AFP fractions • Bx – Not 100% Sn - -ve Bx – doesn’t R/O HCC • STAGING, PROGNOSIS • Prognosis – Tr stage at diagnosis, underlying liver status • Staging & Prognostic systems – • Recognize end-stage d/s • Not universally reproducible • BCLC – Tr burden; Liver Function; Ca related symptoms • 4 stages • Each stage - its own prognosis prediction, appropriate treatment strategy
• Multiple satellite lesions in HCC develop due to involvement of • A. Portal V • B. Hepatic A • C. Hepatic Venules • D. Intrahepatic lymphatics • Ans? • Portal Vein
SURVEILLANCE FOR HCC
RADIOLOGY - USG • For Surveillence – Sn – 60 – 90%; 6 monthly better than annual; • USG screened Cirrhotics – improved median survival & OS – in CHILD B, not in CHILD C • Small HCC tumors (< 5 cm) - hypoechoic OR hyperechoic(fatty metamorphosis) • Larger HCC – heterogeneous(liquefaction necrosis, fibrosis). • Sonographic depiction of HCC - limited in severe cirrhosis • HCC – PV/ HV thrombosis • Tumor v/s Bland thrombus – • CEUS – best characterize lesion > 2 cm • AHE, PV washout – typical feature • 22% HCCs – delayed venous washout • FLHCC – variable echo; Calcification, central scar,(30-60% pts) LAP Tumor thrombi Bland thrombi Expand PV Expand PV Spectral Doppler – Hepatofugal Arterial flow Spectral Doppler - Noise
RADIOLOGY – CECT • HCC Diagnosis in CECT – difficult in cirrhotic livers • Enhancing PV Tumor thrombus – high Sp for HCC in cirrhotic liver
LIRADS – DEFINITELY HCC CRITERIA EITHER OF Major features Enhancing tumor + in PV Washout appearance, -Diameter >/= 1 cm, < 2 cm - Hypervascular - At least 2/3 major features, Enhancing Tr capsule -Diameter >/= 2 cm -Hypervascular, - At least 1/3 major features Threshold growth(Dia increase >/= 50% in < 6 mths >/= 100% in > 6 mths New lesion > 1 cm • FLHCC • Unenhanced CT - hypoattenuating large solitary mass , welldefined margins • Central scar. • Calcification (Differentiate from FNH) – in 35% to 55% of tumors • A, PV phases - Nonscar portion of tumor – heterogeneous enhance • (FNH - homogeneous arterial enhancement around central scar) • Delayed phase - increasing homogeneity, occasional scar enhancement • Pseudocapsule - liver surrounding the mass • may be compressed • Vascular invasion/lymphadenopathy/Lung/peritoneal mets
RADIOLOGY HCC - MRI • Hypo T1, hyper T2-weighted images • APHE, Delayed Phase WashOut(DPWO) • Signal intensity may be variable for < 2 cm HCCs • Large HCCs – T2 phase – mosaic pattern(Tr necrosis) • Intracellular lipid - important clue to small • DPWO – Sp only for Mod/Poor diff HCCs • Well diff HCCs – may not show DPWO • Peri-tumoral capsule – enhanced in delayed phase • FLHCC • Central scar – T1 & T2 - low signal intensity(FNH – Central scar - high T2)
HVPG> 10, EG
• BCLC Stage wise survival • Treatment Stage Migration • BCLC Assessment prior to Rx • Backgrund liver function – CTP scoring • Tumor characteristics – Satellite nodules, PVT, Extrahepatic spread, Vascular invasion • Extrahepatic spread – CT Chest, Bone scan • If expected LTx wait period > 6 mths – Percutaneous Rx • RFA/MWA; PEI (Subcapsular Tr, GB/ Heart near Tr) • Ablation best results – Size < 2 cm – recurrence rates = resection EARLY (A) 5 yr – 50-70% INTERMEDI ATE(B) 3 yr – 66% ADVANCED (C) < 1 yr
• More advanced (unresectable/large/multifocal HCC) , NO PV invasion  TACE (if liver function preserved + Good PS) • If chemoembolization not feasible but preserved liver function (CTP class A or B) + Good PS - , OR advanced stage sorafenib
IMAGE GUIDED ABLATION - HCC • Indication – early HCC • Single tumor <5 cm OR </= 3 nodules < 3 cm—when Sx precluded • Very early stage Trs (</= 2 cm) • Limited unresectable hepatic mets (esp CRLM) • Global Ablation Margin(A0) – Tr free margin 5-10 mm •
Method Crux Advantages Disadvantages RFA -Highfrequency (375-480 kHz) A/C -Target cell death – Frictional heating -USG/CT guided High rates of local control </= 3 cm Tr Estd safety profile Known limitations Experience in combination Rx (HCC) Widely available High incomplete ablation rates in >3 cm Tr Heat-sink effect (“heat sumping”) - perivascular tumors(vessel>3mm) Thermal injury risk to critical str. Variability in RFA devices MWA -EM wave radn from probe Excite water within soft tissue “broadcast” at freq 900 - 2450 MHz -2 cm tissue sphere around probe Ablate Trs 3-5 cm dia in 5-8 min Less impacted by heat-sink effect Can activate multiple probes at same time No grounding pads required Efficacy data, safety data - limited Thermal injury risk to critical str (and vessels?) Variability in devices Cryo 17 gauge Ar cryoprobes/Liquid N2 Target tissue phase change Therapeutic iceball formnCell lethal isotherm (- 30 to -40 degree) Can activate multiple probes at the same time Can image the ice-ball formation Insufficient clinical data Risk of bleeding Risk of cryoshock IRE nonthermal ablation mS D/C current pulses Btw parallel monopolar probes within the Tr. Rx Trs near critical str( spares collagen/ conn. Tissue str) Heat-sink effect not relevant Insufficient clinical data Neuromuscular blockage, cardiac gating reqd
• Local Recurrence after RFA – factors • Tr size > 5 cm • Tr Close to major vessel • Subcapsular Tr location • Intentional margin < 1 cm • Lack of vascular occlusion • Physician experience • Complications • IRE. • MWA - bleeding, bile leak, liver abscess, PVT • RFA • Other Ablation techniques • HIFU - Thermal ablation Rx – Acoustic energy  convtd to heat coag necrosis • Adv – No BV injury (No direct dependence on thermal energy) • Tr locn -< 1 cm from IVC, PV, or a main HV • PEI – Absolute alcohol/Acetic A – Coag necrosis- Lowest cost • Complete radio-response – 100% if Tr < 2 cm • Indications - • Smaller HCCs not amenable to RFA ( near major vascular structures/GB/Hilum)
METHOD OF ABLATION COMPLICATIONS MWA Bleed, Bile leak, LA, PVT RFA Bleed, Bile leak/Stricture, LA, pleural effusion, pneumothorax, hypoxemia during treatment, S.C hematoma IRE PVT, pneumothorax, biliary occlusion, arrhythmias Cryo Bleed, biliary injury, LA, liver shearing,,“cryoshock.”
HAE, TACE • Only 20% to 30% HCCs - candidates for curative Sx(resection, LTx) • Recurrence > curative resection - 50% - 70% at 5 years • Principles – • 90% to 100% of liver Tr BS – Hepatic A • Selective HAE  selective ischemic damage to Tr, spares normal liver (PV) • Hepatic Drug exposure if given through HA compd to systemic V - • Max for 5-FU(10*)>Mitomycin C(8*)>Cisplatin(7*)> Doxo(2*) systemic V admn • Tr stage/type • Encapsulated nodular HCC(HA) v/s well difftd Extracapsular infiltrating advanced HCC(PV/PV+HA) • Mets – whe < 200um – sinusoidal blood); midway – arterialized; but even if advanced – distinct PV supply.
• Targeted tumor ischemia(embolization) + intraarterial chemotherapy • MC used – doxorubicin • Mixed in water/ water soluble contrast  mixed with lipiodol; • Water in oil type emulsion
• Excess Lipiodol - flow back into PV via arterio- portal communication (“plastic” nature adjusts to microvessels size) • Transient arterial and • Portal embolization of HCC  Rx extracapsular infiltrative Trs, satellite nodules(perfused via portal venules). • Lipiodol – retained 6-12 wks in Tr cells only(Absent Kupfer cells) • F/B Lipiodol infusion HAE • Optimal size of embolizing material – small to occlude terminal Arterioles v
• Embolising Agents – • A-P shunts – more in large Trs – embolise before TACE • INDICATIONS • MC – Unresectable HCC • Preserved liver function (Child-Pugh A or B7, PS(ECOG 0/ 1). • 1st line Rx - BCLC intermediate stage HCC (multinodular/asymptomatic Trs, no vascular Invasion/extrahepatic spread) • Alt Rx with curative intent – early stage HCC not fit for resection/ ablation(comorbidities/ anatomic problems)
• CONTRAINDICATIONS – • CPS >/= B8 • Extensive Tr - massive replacement of both lobes of the liver • Major PV thrombus • Active UGI bleed/Refractory ascites/HE • Renal insufficiency/Anaphylaxis to contrast/severe PVD/Uncorrectable coagulopathy • INDICATIONS • Spontaneous rupture of HCC – Emergency TACE regardless of underlying liver function. • Nodular HCC showing exophytic growth – even in advanced cirrhosis TACE to prevent tumor rupture • Hypervascular metastatic lLiver Trs – NETs, GISTs, uveal melanoma
• Doxorubicin dose - 20 to 75 mg – max 150 mg. • Lipiodol upper limit - 15 mL. • End points for emulsion administration - stasis in tumor-feeding arteries +/- Lipiodol appearance in PV branches • Therapeutic efficacy – • Tr necrosis extent - 60% to 100%. • Mean necrosis – selective TACE (75%)> Lobar TACE(52%) • 2-year survival of TACE in HCC > conservative management • TACE - benefit in 2 yr survival +; absent in HAE. • TACE as neoadjuvant Rx before liver resectn– No improvement - reduces resectability; increases operating time. • TACE as bridge before LTx - drop-out rate due to tumor progression – lower(3.0 - 9.3%) if mean waiting time on LTx list > 6 months • MS-GEP-NET – TACE as first-line Rx - 70% complete sympt. Response, 20% partial response. 5yr & 10 yr survival rate - 83% & 56% if used as first line Rx
COMPLICATIONS - TACE • 4% • R/F – • Major PV obstruction • Compromised FLR • Biliary obstruction • Previous biliary Sx • Excessive Lipiodol use • Nonselective embolization • PES – Post Embolization syndrome • 60% - 80% of pts • Pain, fever, nausea, vomiting • Type of tumor lysis syndrome - Abrupt tr cell death by ischemic damage  intracellular toxins into circulation • Transient, non specific • Antiemetics, analgesics, and antipyretics. • ALF – 20%(3%- IRREVERSIBLE) • Liver Abscess – rare – 0.5 – 2% • Prior BEA/SOD – R/F
• BDI – • Peribiliary plexus – from hepatic A. • 2% - 12.5% • Manifestation - intrahepatic biloma, focal stricture of CBD, diffuse dilation of IHBR • MC in - Mets, noncirrhotic liver, and in selective embolizn of distal hepatic A • NTE(Non Target Embolizn) – MC – GB • Skin – Int mammary A, Intercostall A • Gastroduodenal ulcers – LGA, RGA • Pulm. Complicns – Inf phrenic A • IATROGENIC VASC. COMPLICNS – • Coeliac, CHA - dissection
• BLAND EMBOLIZN – MICROSPHERES • Equivalent effect as TACE in Rx of hypervascular Liver primaries & Mets • Inert elastic polymer with hydrophilic surface • tris-acyl gelatin microspheres (Embosphere); spherical PVA; Bead Block; polyphosphazene coated polymethylmethacrylate microspheres (Embozene) • DEB- TACE • DEB – release drugs at target tissue for extended time • 2 types of DEB - PVA based Microspheres, Superabsorbant polymer(SAP)[Hepsph./Quadrasph.] • PVA – 100 – 900 um hydrogel microsph. • Objective response - DEB-TACE (51%) >cTACE group(44%) • Objective response margin DEB TACE V/S c TACE – Higher in – • Child-Pugh class B, ECOG 1, bilobar/ recurrent d/s • DEB – Better tolerability, Reduced liver toxicity • No diff in TTP, OS
RADIOEMBOLIZATION • Nolan & Grady – First studied – Y90 in metal particles 50-100um – HA • Y90 Microspheres (detail) • Pre-Treatment – ECOG> 2 – Not RE candidate • Pre-Rx Diagnostic mesenteric angiogram  Vascular anatomy, Patency PV, A-P shunts • Coil embolization of non target vessels • Inferior esophageal, L inferior phrenic, Accessory left gastric, supraduodenal, retroduodenal A • Tc99m Macroaggregated Albumin scan – for assessing splancnic/Pulmonary shunt (Extrahepatic shunting)
CARRIERS FOR RE
INDICATIONS • IHCC – RE warrants further invx • SECONDARY LIVER TUMORS • IN PRIMARY HCC • Pts within Milans criteria – Bridging to LTx • Pts outside Milans but no Malignant PVT/Mets – downstage, bring to within Milans • Advanced liver d/s – • Malignant PVT – not a CI for RE with Y90 – Have shown favorable response • Survival benefit(10-13 months) in vascular involvement • Y90 – has minimum embolic effect, so not CI in Malignant PVT • Compd to chemoemb – RE – lower TTP, lower toxicity
• MS Trs candidates for RE • MS CRC • MS NETs(unresectable, progressive d/s – Favorable factors - BR<1.2, ECOG 0) • MS Mixed Neoplasia (Ca breast) • MS Melanoma (Y90 – favorable factors – Child A, <10 liver mets, no extrahep mets) • Post Rx F/U – • 1st Radiological F/U – 1 mth > Rx • Earlier than 6 mths – f MRI is best • RECIST & EASLD Tr necrosis criteria used • COMPLICATIONS • Post radioembolizn syndrome(Fatihue,Nx,Vx,Fever, Abd sympt) • Hepatobiliary toxicity(BR,Alb,Enz; VOD-like) • Radiation pneumonitis(CT – Batwing app) • PHTN – RE causes FIBROSIS - Usu in bilobar d/s, CASH pts) • Biliary – Biloma, Abscess cholangitis • GI complications – Inadvertnt microsph deposit Ulcer - CT Angio, PPI prophylaxis • Vascular
CHEMOTHERAPY FOR HCC • SHARP TRIAL • Phase III study • Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol) trial • Improvement in survival of 10.7 months in sorafenib group v/s 7.9 months for placebo arm
PREOP PVE • By – Maakuchi • INDICATIONS – • Sflr - insufficient to permit safe hepatectomy(quality of underlying liver, type of planned hepatectomy) . • Absolute contraindications for PVE: • Estd Portal HTN (>10-15 mm Hg) • Extensive Tr Thrombus
• C/L approach for R PVE. • Occlusion balloon catheter – through L lobe into the RP branch • Embolic agent delivered in antegrade direction
• I/L approach for RPVE extended to segment IV (Nagino et al) • Different • balloon catheters are used for B1 antegrade embolization of segment IV veins, and B2, retrograde delivery of the embolic agent into the right portal • venous system.
• Modification of I/L approach for RPVE extended to segment IV. • C1, vascular sheath - in RP branch  5-Fr catheter – in LP system  microcatheter into seg IV branch. Particulate embolizn  Coil placement--until all the branches are occluded. • C2, After seg IV is completely occluded  reverse-curve catheter for RPVE. • C3, Access tract embolized with • coils - prevent subcapsular hemorrhage.
PREOP PVE Trans-ileocolic Venous P.C Transhepatic C/L(Kinoshita et al) P.C Transhepatic I/L(Nagino et al) First approach introduced Laparotomy USG guided; Seg III approach; Subxiphoid route; 18 G/22G PV branches within tumor- bearing liver Ileocolic V cannulation PV catheterizn RAPV puncture - Addnal Rx needed during Sx explorn - IR suite NA, P..C approach NA DISADVANTAGE GA, Laparotomyneeded Inferior Through the FLR!!  LPV thrombus/Injury to FLR No multiple pricks, No injury to central str to be done! can be challenging - sharp angles of the RPVs – use reverse curve Catheters ADVANTAGE RPV Catheterizn – easier – no need of awkward angles better visualization of embolized portal br. on final Catheters through the FLR. I/L approach - straightfwd antegrade catheterization of
• OPTIMAL EXTENT OF PVE – • RPVE – L lateral bisegment hypertrophy is greater after RPVE + Seg IV (50% inc) than only RPVE (31% inc) – Nagino et al • LPVE – rarely needed • SEQUENTIAL AE PVE • Rationale – • HCCs - hypervascular, supplied by arterial BF – PVE  compensatory “arterialization of liver”) in embolized segment rapid Tr progression > PVE. • Arterioportal shunts in cirrhotic livers & HCC may limit effectiveness of PVE • Sequential AE  PVE – FLR > that in PVE alone • SAE PVE – Tr necrosis > PVE alone • SAE – PVE Time gap – at least 3 wks recommended • Degree of Hypertrophy(DH)(>5%/s FLR>20%); Kinetic Growth Rate(KGR) (>2% /wk) – low postop morbidity.
COMPLICATIONS • S.C hematoma • Hemoperitoneum, • Hemobilia • Arterio-portal shunts • A-V fistula, pseudoaneurysm • Transient liver failure • Pneumothorax • Sepsis. • Risk of injury to FLR with C/L approach – so, I/L approach should be tried first • Overall incidence of complications with either pproach – 5% • OUTCOMES – • Longterm – in HCC • No difference in PVE & Non PVE pts in OS/ DFS
ALPPS • Hans Schlitt • Associating liver partition and portal vein • ligation for staged hepatectomy • ALPPS = R PV Ligation + In situ splitting of liver • INDICATIONS – • 1st done in Hilar cholangioCa • Bilobar CRLM • HCC in cirrhotic liver • PHC & IHC – Controversial • Indications – same as 2 stage hepatectomy, PVE/PVL • Rescue ALPPS – ALPPS wen classic 2 Stage approach/PVE – Not feasible/failed • Extrahepatic metastases, • Severe portal hypertension • High Anesthesiologic risk • Medical contraindications to major hepatectomy
• (FLRV) before surgery, reevaluated before the 2nd stage • Measured by CT volumetry • Cut-off values fto proceed to stage 2 (> 7 - 14 days ) - sFLR > 30% (BWR > 0.5%) 40% (BWR > 0.8%) • FAILED ALPPS – • Anterior sectional PV from LPV missed during surgery deportalization of the R liver lobe – incomplete reduced hypertrophy of the FLR • Undivided PV at hilum – Absolute contraindication for ALPPS • Smadja & Blumgarts Type A & Type B – faborable for ALPPS • Type C & Type D – High risk of biliary complications > stage I ALPPS • Type E – risk of damage to L Bile duct @ stage 2 ALPPS • MHV should not be transected @ stage 1 ALPPS unles infiltrated by Tr – (To maintain the outflow to FLR)
STEPS of R ALPPS/CLASSIC ALPPS Liver mobiliseLAD of hepatic pedicleRPV lign, transctn; liver transection hanging maneuver(anterior approach) Results – Volumetric redn of de-portalized liver(Auxillary liver), hypertrophy of FLR – Fibrin sponge/plastic bag on cut
• Usual waiting time – 1-2 wks • Min s-FLR – 30% -40% depeding on liver qlty • Mechanism • ISS(In Situ Split) – cuts off Intrahepatic Portal collaterals to ipsilateral liver • Sx trauma to liver – cytokines  growth stimuln • But – compensatory hyper-perfusn by Hepatic A • COMPLICATIONS • MC – Biliary fistulae, collections, Sepsis • Most severe complication – Liver Failure Stage 2 – RHA RHD Divided, RHV+/- MHV - divided deportalised Liver removed
• Technical detail to improve results • Accurate 3D volumetric calculation • Colored plastic loops during stage 1, • Intraop cholangiography • White test to detect biliary leaks at end of stage 1, • Preserving of MHV when possible • TIMING OF STAGE 2 ALPPS – • Clinincal condition good; No Sx complication • Not always @ 2 wks • Interval > 2 wks – increased difficulty stage 2 • OUTCOMES • Perioperative 90-day mortality - 9% • Severe complications, including mortality (grade > IIIa) - 28%. • Packed cell/ Stage I duration > 300 min/Age > 60 yrs/Indication of ALPPS(Primary HCC>CRLM) – significant R/F. • Leading cause of death & severe complicn post ALPPS - POLF
Classic ALPPS – R ALPPS Central ALPPS – Division along Cantlies line btw R & L livers
L ALPPS – Tr in L side – seg VI, VII = FLR Central ALPPS – Stage I – L lateral sectionectomy + RPVL Stge 2 – R hemihepatectomy – FLR =Seg I, IV
TYPES OF ALPPS
• Pringle Maneuver involves clamping of A. PV Only B. PV, HA C. PV, HA, CBD and Lymphatics D. Hepatic A Only • End point of Pringle Maneuver? • Pringle Maneuver Applied, Unsuccessful – What are the probable scenarios? • Normal Liver can tolerate Inflow occlusion under normothermic conditions for? • Diseased liver can tolerate inflow occlusion under normothermic conditions for?
PEDICLE CLAMPING • HD response to PEDICLE CLAMPING • Easiest method to reduce bleeding in Liver resectioninflow control. • Pedicular clamping – minimal HD consequence + greatest efficiency(Low filling) • Continuous clamping - ischemic injury to liver parenchyma + splanchnic congestion. • Intermittent clamping has supplanted continuous clamping – GOLD STANDARD METHOD Cardiac pre-load Mild- Mod decrease PAP 5% decrease Cardiac index 10% decrease MAP INCREASE!!!(Symp. Reflex, SVR) Recurrent clamping-declamping cycles  Hypotension Ischemia-reperfusion; toxic VD accumulation
• WOTF is Not a side effect of continuous clamping for inflow control during liver resection? A. Post-op ileus B. Abdominal Compartment Syndrome C. Pancreatitis D. Spontaneous splenic rupture E. Hypotension F. None of these
• HD Response to THVE • SEQUENCE OF THVE – Pedicle Infra Supra • Compensatory response to THVE – 5 min – Facilitated by bolus IV flds(PRELOADING) • MAP fall to < 80 mm – Intolerance of THVE  Declamp, optimize Cardiac preload Severe decrease PAP 25% decrease Cardiac Index 40-50% decrease MAP 10% decrease HR 50% increase SVR Severe increase
• INTERMITTENT CLAMPING • MC used vasc. Clamping method • 15 min clamping. 5 min reperfusion (Unclamping) • Unclamping => No parenchymal transection • Cumulative clamping – upto 1 hr in D/S LIVER • 3 hrs – in normal liver • BEST IN DONOR HARVEST OF LIVER – No compromise in Donor safety/ Graft qlty • ISCHEMIC PRE-CONDITIONING • Initial ischemia time(10 min) F/B Reperfusion(10 min) • Protects liver against prolonged ischemia • Benefits of IPC – Only for 30 min of continuous clamping & for small vol liver resection • PHARMACOLOGICAL PRECONDITIONING • 30 min intraop preconditioning with sevofluorane – reduced postop AST & ALT • Postop complications reduced • Benefits strongest in hepatic steatosis pts
Clamping Tech Tech. difficulty HD Tolerance Liver Tolerance Bleed Prevention Contraindicn Complicatio ns No clamping - Most Most Least - Bleed, needing BT Intermittent Pedicle clamping Least Most Intermediate Intermediate - - Continuous pedicle clamping Least Most Least Intermediate D/s liver Splancnic congestion Partial pedicle clamping Intermediate Most Most Most Pedicle involvement - Pedicle + Infrahepatic IVC clamping Least Intermedi ate Intermediate Intermediate Low CVP - HVE(Classic) Intermediate Least Least Least D/s liver/ Cardiac D/s Splancnic congestion; AKI Intermittent HVE + IVC flow preservation Most Intermedi ate Intermediate Most Juxta-caval Tr -
• MC indication of partial hepatectomy – Metastatic lesions • Benign lesions • Malignant lesions – ideal closest Tr free margin – 1 cm; but not necessary – unavailable –ve margin in pre-op imaging – Not CI for resection • Parenchyma-sparing resections - without sacrificing oncologic efficacy • Minimal/ no risk of POLF exists if most of the specimen volume has been replaced by extensive tumor mass  compensatory hypertrophy of unaffected residual liver occurs preoperatively  limited functional parenchymal loss • Comparable resection for multiple smaller lesions or unfavorably located lesions  greater risk of POLF.
ANTERIOR & POST SECTIONECTOMY, CENTRAL HEPATECTOMY
ANESTHETIC CONSIDERATIONS • Bleeding in Liver resection- usu. during parenchymal transection -from HV or IVC • Deliberate retrohepatic dissection of minor& major HV before parenchymal transection – Unless the Tr location & size mandate anterior approach. • Minimal CVP < 5 mm Hg • Healthy patient – Central line not needed • 15 degree Trendelenberg position(prevent air embolism)/neutral/reverse trendelenberg • Low IVF till transection complete/Venodilator • Avoid peri-op BT – ADVERSE Periop outcome, ?increased recurrence • Indications of BT in LR - • Excessive blood loss • HD instability / Hb < 7 g/dL. • Acute Normovolemic hemodilution • Vascular isolations – Rarely used, even for Large Trs
• STEPS OF HEPATECTOMY • Exposure • Vascular – Inflow/Outflow ctrl • Parenchymal Transection • PARENCHYMAL TRANSECTION p1584, Blumgart • Digitoclasty/Finger #/Clamp crushing – spare vessels & BD along transection plane • Hydrojet(Waterjet based device); CUSA – Parenchmal destruction & vessel, BD preservation • V/S Digito/finger/clamp – greater accuracy, +/- increased speed - poor hemostasis • RFA based – Tissuelink, AquaMantys, Habib4X – Hemostatic devices – Rapid indiscriminate coagln cut surface- • Bipolar(LIGASURE), US vessel seal(Harmonic scalpel) – seal BV 7-8 mm dia. • Stapling devices – Ctrl large vessels in plane OR as primary method of transection
ANTERIOR APPROACH, HANGING MANEUVRE(Lai et al) • INDICATIONS – FOR RIGHT HEPATECTOMY • Larger Trs invading diaphragm • Invading lateral wall of IVC higher • Large HCCs/Adenomas – which may # or bleed during mobilization • May avoid risks of massive bleeding from HV avulsion, prolonged ischemia in remnant liver, spillage of cancer cells • HANGING MANEUVRE • To ctrl bleed in deeper parenchymal planes • Pre-requisite – Absence of Tr in contact with anterior IVC wall
• Exposure of liver at level of suprahepatic IVC • Dissect btw MHV & RHV for 2 cm • Expose liver @ level of infrahepatic IVC • Caudate lobe tributaries to IVC –ligated, divided • Dissection of plane anterior to IVC – Kelly clamp – upwards btw IVC, Caudate comes out btw RHV & MHV • Umbilical tape passed thru this tract lift liver away from IVC • RPV, RHA divided • Parenchymal transectn(with pull on umbiical tape) exposed deeper planes easily • IVC protected by umbilical tape traction • IVC exposed  dissection of R side IVC wall to separate it from Tr • Division of Hepatocaval lig, RHV, RIHV - now
PARENCHYMA SPARING LIVER RESECTION TECH. Mini-Meso hepatectomy – Seg VIII, Part of seg I – Tr invading MHV 4 cm from MHV-IVC confluence R Posterior sectionectomy – for posteriorly located Trs
• Upper Transversal Hepatectomy – for Trs invading RHV – IVC confluence • Redefining ANATOMICAL RESECTION – Removal of territory of one or more 3rd order portal br. • Assisted by – IOUS, NIR fluorescent imaging, Biliary/ Vascular injection of ICG • RH v/s RPS – POLF – more likely in RH; severe liver insufficiency – RH> RPS; No diff in OS/ Other short term parameters
CRLM • PRE-OP EVALUATION • Med. Resectability(PS, Comorb, liver status) • Oncologic. Resectability(Tr markers, Rdio- resectability, Scopy) • Technical resectability (Volumetric) • CECT Abd, Chest, Pelvis • MRI - Indeterminate lesions; Liver-sp. Contrast sub cm lesions in S.C location; in Macrovesicular steatosis • PET-CT – prior to Metastasectomy, suspected recurrence, RT planning, response assessment, Incidental CRLM discovery (occult omental/ peritoneal d/s) • Evaluate indeterminate nodal/ST mass on CT/ MRI; • unremarkable scans but elevated CEA level out of proportion to liver d/s.
liver copy.pptx
liver copy.pptx
liver copy.pptx
liver copy.pptx
liver copy.pptx
liver copy.pptx
liver copy.pptx
liver copy.pptx
liver copy.pptx

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liver copy.pptx

  • 2. • LIVER ANATOMY • LIVER PHYSIOLOGY • LIVER FUNCTION TESTS – ENZYMES, ESTIMATION OF REMNANT • RADIOLOGY – SEGMENTS • DILI; CHOLESTASIS • ALF, LIVER SUPPORT SYSTEMS • ISCHEMIC HEPATITIS • HEPATIC TRAUMA • HEPATIC CYSTS • HYDATID LIVER • LIVER ABSCESS – ALA, PLA; • HEPATIC BENIGN NEOPLASMS
  • 3.
  • 4. • Invested with peritoneum except posteriorly • Posteriorly - peritoneum reflects onto the diaphragm – forms R & L triangular ligaments.
  • 5. • RHV - largest – short extrahepatic course – 1- 2 cm • LHV & MHV – drain separately/ common venous channel 2 cm long – to L of IVC, infra- diaphragmatically • Umbilical vein- MC single - • runs beneath falciform – btw MHV & LHV – into - into – LHV(MC)>MHV> Confluence • 15% patients - accessory RHV - present inferiorly • Caudate lobe – HV drainage -directly into the IVC
  • 6. • R portal triad – short extrahepatic course - 1 - 1.5 cm • L portal pedicle - 3 - 4 cm beneath segment IV – separated fron segment IV by Hilar plate (connective tissue) enters umbilical fissure • branches of L portal pedicle – supply segment II segment III, recurrent(feedback) branches to segment IV • Beneath segment IV - pedicle has – LPV, LHD – Joined by LHA later at the base of the umbilical fissure
  • 7. • 3 Portal Scissurae (PS) – with HV – divide liver into 4 sectors (Couinaud)/ Segments(Goldsmith)/ Sections(IHPBA, Brisbane) - each sector receives a portal pedicle. • MPS – has MHV – Cantlie line – divides liver into R & L • RPS – Has RHV – R liver into RA Sector, RP Sector • LPS – not in umbilical fissure – inside liver, carries LHV; Umbilical fissure has Portal pedicle
  • 8.
  • 9. CAUDATE LOBE • Anterior surface within parenchyma - covered by posterior surface of segment IV the limit an oblique plane slanting from the LPV to LHV. • Constant L portion (Spheigel lobe/Papillary process) & variable R portion(caudate process/segment IX) (size).
  • 10. CAUDATE LOBE • Major blood supply – arises from left branch of LPV & LHA close to base of umbilical fissure • The hepatic veins (MHV, LHV) -short in course – drain from caudate directly into the anterior & left aspect of IVC
  • 11. CAUDATE LOBE • Anterior to IVC • Posterior to PV • B.S – mainly by LPV • Occasionally, br. From MPV
  • 12. CAUDATE LOBE • Caudate mobilisation from Left side • Caudate branch of portal V, Veins from IVC – divided • Tunnel between the MHV - LHV & IVC – to clamp
  • 13. CAUDATE LOBE • Various approaches to Caudate lobectomy • Lesser omentum opened – Caudate Br of LPV divided • Ligamentous attachments of caudate lobe divided – Retrohepatic V divided – Caudate this approaches from left / Right
  • 14. CAUDATE – BLOOD SUPPLY, VENOUS DRAINAGE • Caudate Blood supply, biliary & venous drainage – from R and L portal triad. • The RCL including the caudate process, predominantly receives PV blood from RPV/ from MPV bifurcation. • LCL - portal supply - from the LPV exclusively. • Arterial supply & biliary drainage of the RCL - most commonly associated with RPS vessels; LCL blood supply and biliary drainage – with L main vessels. • HV drainage of caudate - unique - the only hepatic segment that drains directly into IVC. • Some Veins from R Posterior section and caudate lobe drain directly into the IVC. • Can sometimes drain into posterior aspect of IVC if a significant retrocaval caudate component is present.
  • 15. PORTAL VEIN • PORTAL VEIN • High flow, low pressure (No valves – PV press measured anywhere along PV) • 75% of Liver BF, but 50 – 70% of Liver O2 reqt(due to high flow) • 5.5 – 8 cm long, 1 cm diameter; • Formation – behind pancreas neck – SMV, splenic V • Inside lesser omentum – receives coronary V • Larger RPV (RA, RP, Caudate process), smaller LPV(Caudate br. Before umbilical fissure; • Most constant anatomy among portal triad
  • 16. HEPATIC ARTERY • HEPATIC ARTERY • 25% of the Liver BF, 30 - 50% of oxygenation. • High flow, high pressure • RHA – usually posterior to CHD – enters Calots – gives cystic A • LHA – into umbilical fissure; to the R of fissure – gives segment IV A • Hepatic A anatomy – Highly variable
  • 17. H.A VARIATION • Variations – • Accessory vessel – in addition to original • Replaced vessel – substituting original vessel • Replaced/Accessory RHA – from SMA – 11- 21% • Replaced/Accessory LHA – from LGA – 4-10% • GDA – from – CHA/RHA • Cystic A – anywhere from Coeliac axis to RHA Michelles classification I Normal Anatomy II Replaced LHA from LGA III Replaced RHA from SMA IV Replaced RHA & LHA V Accessory LHA VI Accessory RHA VII Accesory RHA & LHA VIII Replaced RHA/ LHA with other hepatic artery being an accessory one IX Hepatic trunk as a branch of the SMA X CHA from LGA
  • 18. • NERVE SUPPLY • Sympathetic fibres from T7 - T10  through coeliac ganglia • Parasympathetic fibers from both vagal N • R sided Coeliac ganglia & R Vagus  Anterior hepatic plexus – along hepatic A • L sided coeliac ganglia & L Vagal N – Posterior Hepatic plexus – posterior to BD, PV • Hepatic A – sympathetic; BD and PV – parasympathetic • LYMPHATICS • HDL; Hepatic A  Coeliac LN  Cysterna chyli • OR • HV  Suprahepatic IVC/ Diaphragmatic hiatus
  • 19. MICROSCOPIC ANATOMY • Hepatic parenchyma - microscopic functional units – acinus/ lobule • Central terminal hepatic venule (HV) surrounded by 4 – 6 terminal portal triads (PT) - polygonal unit • PT – in connective tissue – space of MALL • Btw HV & PT – Hepatocytes – in one-cell-thick plates - surrounded on each side by sinusoids. • Blood flow – PT  HV • Bile flow – Biliary canaliculi (lateral walls of hepatocyte)  Bile ducts  PT
  • 20. • PV, Hepatic Arterioles(HA) – blood supply to sinusoids • PV & HA flow inversely varies in sinusoids • Sinusoid BF - PV component – constant, minimal; HA component – pulsatile, low volume • Sinusoids - 7 -15 μm wide - can increase in size by up to 10-fold  low-resistance and low-pressure (2 -3 mm Hg) • Zones – 1, 2, 3 – from PT  HV • Zone 1 (periportal) – high nutrients, oxygen. • Zone 2 (intermediate) • Zone 3 (perivenular) - low oxygen, nutrients
  • 21. • Space of (SD)– perisinusoidal space – exchange of proteins, plasma components btw Hepatocytes, sinusoids. • Endothilial cells in SD – lack BM, Inter-cellular junctions; have fenestrations – Bidirectional mmt of high, low molecular wt solutes
  • 22. Cells of Liver Hepatocyte(HC) Kupffer cell Stellate cells(Ito cells) NK cells, CD4, CD8 cells 60% of hepatocellular mass, 80% of cytoplasmic mass Line sinusoids among endothelial cells In Space of Disse Innate immunity in liver Has surface contact with – Adjacent hepatocytes,bile canaliculus & perisinusoidal space Phagocytic High retinoid content Sinusoidal membrane- microvilli – with Disse – blood- HC solute exchange Migrate along sinusoids to injury site vitamin A storage/ synthesis of collagen, ECM proteins Lateral domain – HC-HC interface - intercell communication Initiate inflammation Change to myofibroblastic phase in liver injury (less vit A production, more ECM, cellular contractility Canalicular membrane – HC- canaliculi interface – Zona occludens Express MHC II Ags Progression of fibrosis to cirrhosis
  • 23. HEPATOCYTE MICROSOMAL FUNCTION • Hepatocyte Mt – 1000/cell; 20% of cell mass; ATP via oxidative phosphorylation; Fatty acid oxidation; • HePar-1(Hepatocyte Paraffin-1) – Antigen on hepatocyte Mt – Hepatocyte Trs • Hepatocyte microsomal fraction – interconnected membrane complexes – SER, RER, Golgi complex – Lipid, glucose metabolism, protein synthesis, cholesterol prodn & metabolism • Function of hepatocytes – dependent on their location in the 3 zones in lobule – FUNCTIONAL HETEROGENEITY • BUT – Under specific physiological conditions – functions can change irrespective of anatomic location
  • 24. ZONES IN LIVER FUNCTION Zones Feature Hepatocye function 1 (Periportal) High substrate conc. Narrow, tortuous sinusoids High O2, solute uptake Glucose Uptake & release, bile formation, Albumin & Fibrinogen synthesis 2 (Intermediate) 3 (Perivenular) Most susceptibe to hypoxia Sinusoids– Larger fenestrations Larger molecule uptake Glucose catabolism, xenobiotic metabolism, AFP, α1-AT Urea cycle enzymes
  • 25. BLOOD SUPPLY TO LIVER • Dual B.S – PV(75% of LBF, 50-70% of O2, though partly de-oxyganated) HA – 25% of LBF • LBF - Reduced in exercise; increased after ingestion of food. • Oxygen conc. – max(85%) in fasting state • Carbohydrates – most profound effect on LBF • Pressure – HA (=systemic BP); PV – 6-10 mm Hg, Sinusoids – 2-3 mm Hg • Factors controlling LBF – ANS, hormones, Bile salts, metabolites; Endogenous subst • As portal perfusion decreases, hepatic arterial flow generally increases (Hepatic Arterial buffer response – LAUTT et al) – by Adenosine washout • HABR - capable of buffering 25% to 60% of the decreased portal flow; increases LBF by 30%
  • 26. HEPATIC VEIN • Free pressure in HVs & IVC - 1 to 2 mm Hg; 1 - 5 mm Hg lower than sinusoidal & PV pressure • Portal pressure gradient, defined as the difference in PV and IVC pressures - • Pressure gradient in the liver is thus extremely low - 5 mm Hg
  • 27. PHYSIOLOGY OF HEPATIC SINUSOIDS • Hepatic sinusoids – • Absent BM • Endothilial lining with fenestrae(arranged in clusters of 10-50 pores– sieve plates) • Fenestrae –contract & dilate in response to sinusoidal BF changes • HSC – Ito –(Space of Disse) - compress sinusoids by squeezing endothelial cells - ctrl BF through sinusoids • KC (Luminal side) - Secrete large amounts of vasodilator NO
  • 28. • Regarding Portal BF All are true except – a. Ito cells causes contraction of sinusoids b. Endothelin & Endothilium derived NO – cause contraction of sinusoids c. Smooth muscle cells of endothelium cause contraction of sinusoids d. Sinusoids and portal venules are sites of resistance
  • 29. Endothelial mediators controlling vascular tone by acting on HSC contractility agent Function Source Target TXA2 VC, plt Activation, aggregation, leukocyte adhesion SEC, KC SEC, platelet, leukocyte PGI2 VD,platelet aggregn inhibn SEC SEC, HSC AT-II VC HSC HSC NO VD (i NOS) VD(e NOS) SEC, KC, VSMC,HSC, HC SEC VSMC, HSC VSMC, HSC ET1 VD SEC, HSC, KC VSMC, HSC, SEC, KC ET1 VC SEC, HSC, KC SEC CO VD SEC, KC, VSMC,HSC, HC VSMC, HSC H2S VD HSC, HC VSMC
  • 30. • Liver-extrinsic NO - vasodilation in the hepatic arterial & mesenteric vascular beds. • Endothelin - prolonged generalized systemic constriction + direct effect on LBF. • Endothelins reduce hepatic perfusion; increase portal pressure; reduce sinusoidal diameter • Angiotensin - decreases hepatic arterial & portal blood flow - significant vasoconstrictor • effect on the HA. • H2S endogenously or exogenously - reverse the norepinephrine-induced vasoconstriction • SYMPATHETIC NS - HA - both α-adrenergic, β-adrenergic receptors; PV - only α-receptors • Low doses, epinephrine  hepatic & mesenteric arterial vasodilation; high doses,vasoconstriction
  • 31. FUNCTIONS OF LIVER – BILE SECRETION • Water – 85% of bile • Major Organic solutes in bile - bilirubin, bile salts, phospholipids, cholesterol. • Bilirubin – RBC breakdown product • Bile salts(BS) – Steroids – by hepatocytes • Primary (80% of BS) – Cholic, Chenodeoxycholic • Secondary – Lithocholic, Deoxycholic • Phospholipids – by liver – Lecithin MC form(95%) • Cholesterol – 80% synthesized by liver • Normal bile – 750 – 1000 ml/d Stimulate bile flow Inhibit bile flow Vagal stimulation Splancnic stimulation Secretin, CCK, gastrin, and glucagon Major important – rate of hepatocyte Bile Slt synthesis
  • 32. BILE COMPOSITION • Lipids, bile salts, phospholipids, cholesterol - concentrated in the GB
  • 33. BILE SALT, LIPID SECRETION Na dependent Na independent ABC-11 PFIC Phospholipid
  • 34. • Bile acid (BA) – synthesized from cholesterol – CLASSIC(cholic acid), ALTERNATIVE(Chenodeoxycholic) Pathways • BA – from Disse space to hepatocyte • OATP(Organic Anion Transport Protein) – wide substrate affinity, transport many organic ions • OATP-C - major Na-independent BS uptake system • OATP-A - bile acids uptake; OATP- taurocholate uptake. • Rate limiting step in BS secretion – BS transport across canalicular membrane • ABC-11 – Major transport of monovalent BS into the canaliculus • MDR-related protein-2 (MRP2) – transports sulfated, glucuronidated BS into canaliculus – also organic anions, toxins, heavy metals, ABs • Progressive familial intrahepatic cholestatis type 3 - MDR3 deficiency - no phosphatidylcholine in bile – no mixed micelle formn with bile salts – injury to biliary epithelium by BS - resulting in neonatal cholestasis, cholestasis of pregnancy, cirrhosis
  • 35.
  • 36. ENTEROHEPATIC CIRCULATION • Circulating bile pool - total amount of bile acids in EHC • 95% of bile salts – reabsorbed; extracted by hepatocytes • Colon – Bacterial action on primary BS  Secondary BS(Deoxy, litho) • Active steps involved in EHC – Secretion of bile acids from hepatocytes into canaliculi; from ileum/small bowel into Portal Vein • Bile acids – passively absorbed in jejunum • Function of EHC – reusing BA/ Excretion of cholesterol/Absorption of dietary dats, Fat soluble vtamins
  • 37. BILIRUBIN METABOLISM • Heme breakdown – • early phase - accounting for 20% of bilirubin – is from hemoproteins - occurs within 3 days of labeling with radioactive heme • late phase - accounting for 80% of bilirubin - from senescent RBCs – within 110 days • Heme  Green BV(Heme oxygenase) Orange BR(BV reductase) • Circulation – BR-Alb complex  dissociates in Disse space  Free BR into HepatocyteConjugation(UDP Glucuronidase)into bile canaliculi(energy dependent)GIT Deconjugn(bacteria) • Urobilinogens Oxidation into BS Reabsorption  EHC/spillage to urine • Kernicterus – encephalopathy/cochlear damage in neonates – Unconjugated Unconjugated HyperBR Conjugated HyperBR Neonatal; Hemolytic anemia, Enzyme def – Gilbert, Criggler Najjar Cholestasis, Rotor, Dubin Johnson
  • 38. CARBOHYDRATE METABOLISM • Storage, distribution of glucose to peripheral tissue • Storage of glucose as glycogen – Liver, muscle • Breakdown into glucose from glycogen– only by liver • 65g/kg liver – glycogen store; used in post- absorptive state – depleted after 48 hpurs • > 48 hrs – liver shifts to gluconeogenesis – alanine(muscle); glycerol(adipose) • Cori cycle -
  • 39. COAGULATION • Synthesize coagulation factors, fibrinolytic system compnents • Vitamin K absorption, Vitamin K–dependent coagulation factor synthesis • Gamma carboxylation of • Thrombocytopenia, platelet abnormalities, vitamin K deficiency; DIC • Warfarin – acts on liver - blocks vitamin K–dependent activation of factors II, VII, IX, and X. • Hepatic synthetic dysfunction – Abnormal PT/INR
  • 40. IMMUNOLOGY • INNATE – Initial, non specific defence; NK, PMN, DC, Mac, complement, epithelial barriers • Direct kill Tumor/Infectious cells – present Ag to Acqd immunity • ACQD – Later, specific targeted – B cell, T cell MAC PMN NK DC B Cell CD4 CD8 INNATE ADAPTIVE 0 – 12 Hrs 1 – 5 days
  • 41. • APC signals to B/T Cells • Signals from APCs – Antigen presentation; Co- stimulation; Cytokine release • Naïve CD4+ T cells – differentiate into T cells—Th1, Th2, Th17, and Treg • Programmed CD4+ T cells - modulate CD8+ T cells - differentiate into cytotoxic / regulatory cells.
  • 42. • Liver – Tolerance v/s excessive immunity balance • Tolerance - oral tolerance, chronic hepatitis infection, Tx • Drawback of tolerance - distant metastatic disease MC deposited in liver . • Excessive immunity - AI Hepatitis, PSC, PBC. • Immune responses to intrahepatic Ags – if - effector CD4+, CD8+ T cells - not suppressed by regulatory T cells (Treg) OR Immuno- inhibitory pathways (PD1/PDL1) • Tolerance – if Treg/ PDL1/PD1 upregulated
  • 43. CELLS • DC • Myeloid (CD11b+)/ lymphoid (CD8α+) liver DCs (10% of liver DC) - activate T cells, • Remaining DCs(90%) - low-to-no expression of CD11b & CD8α poor T-cell stimulators. • Human liver DCs - weaker stimulators of T cells; produce antiinflammatory cytokine interleukin-10 (IL-10) • KCs • Liver Macrophages • largest pool of macrophages in the body - from monocytic precursors • Location - hepatic sinusoids; also can migrate through space of Disse to interact with hepatocytes. • Antigen presentation, portal venous tolerance. • induce immune tolerance to liver allografts
  • 44. • LSECs • Fenestrations -facilitate the selective passage of Ags btw sinusoid and hepatocyte; • LSECs - capable of capturing various Ags in vivo & in vitro • But cant activate T cells in the absence of exogenous costimulation
  • 45. • Type of APC & presence/absence of costimulatory molecules – determine whether a T cell has no response (anergy) or is activated • Ag presentation by APC to T cell  trigger adaptive immune response unless suppressor cells or immunoinhibitory signals intervene.
  • 46.
  • 47. LIVER FUNCTION TESTS • MARKERS OF CELLULAR INJURY • ALT(Cytoplasm; liver only) – More specific of liver injury >AST(Mt; not only in liver) AST or ALT 100s Mild viral hepatitis >1000 Acute viral hepatitis >3000 Acetaminophen, ischemic liver injury AST or ALT >300 IU/mL, AST/ALT>2 ALD ALT>AST NAFLD/Viral hepatitis AST>ALT Hypoxic/Toxic ALT t1/2 – 17 hrs AST t1/2 – 47 hrs ALT > AST Recovery phase AST significantly raised than ALT Extrahepatic source - myocardial infarction, rhabdomyolysis, strenuous exercise, hemolysis
  • 48. LIVER FUNCTION TESTS • BILE FLOW MARKERS – • Alk Phos – Zinc metalloproteinase – by hepatocyte canalicular membrane • Also - bone, intestine, placenta, kidney, WBC • Increase – childhood(Bone growth); Old age(Bone resorption) • Alk Phose >/= 3 fold –BD obstruction/ Intrahepatic Cholestasis • GGT – non specific; monitor alcohol abstinence if AST, ALT Normal Acute cholestasis Bile duct obstruction Drug-induced cholestasis – Macrolide ABs, Azole antifungals Sepsis-induced cholestasis Parenteral nutrition–related cholestasis Critical illness–related cholestasis Chronic cholestasis Primary biliary cholangitis Hepatic sarcoidosis PSC, IgG4 - cholangitis Drug-induced cholestasis - Chronic bile duct obstruction
  • 49. • SYNTHETIC FUNCTION Albumin T1/2 – 20 days Significant reduction Prolonged/mjor liver d/s PT – (PTThrombin) severe liver dysfunction, dietary vitamin K deficiency, antibiotic administration, vitamin K malabsorption, DIC, drugs (warfarin)
  • 50. HEPATIC FUNCTION ASSESSMENT • VOLUMETRIC • required to assess FLR prior to major ( >4 segments) liver resection • MC – CT/ MRI • FLR volume = FLR/TLV; TLV includes Tumor volume – (apparently high TLV & low FLR) • So – TELV(Total estimated liver vol) – TLV for BSA • FLR/TELV = sFLR • TELV (i.e., sFLR) - better predictor of postoperative hepatic insufficiency • Exact volumetric threshold? • Normal background liver – 20-30% • Post chemotherapy – 30% • Known liver d/s – < 40% - indication for PVE • DH < 20%/ KGR - < 2.6% /wk-
  • 51. • FUNCTIONAL ASSESSMENT • Hepatocyte injury – AST, ALT, ALP • Synthetic – Alb, INR • Hepatic metabolism marker – BR • CHILD TURCOTTE PUGH  CHILD PUGH • Developed to predict the risk of death in surgery for portal hypertension • Now – risk in cirrhotics undergoing varous procedures • 3 Lab tests (BR, Alb, INR) 2 Clinical findings – Ascites, enceph) • If no cirrhosis – CTP will be normal – alternative scores needed • Marker of global liver function in cirrhosis • Patient selection of for liver resection in HCC. • Class A cirrhosis - Sx • Class B – Approached cautiously • Class C cirrhosis – Avoid Sx
  • 52. • MELD – • Initially – prediction of short-term survival in h cirrhotics; now – longterm survival also • Used in LTx to allocate organs. • In Cirrhotic/Partial hepatectomy – MELD >8 – predicts peri-op mortality, less long term survival • If no background liver injury – not useful • HEPATIC UPTAKE, METABOLISM, ELIMINATION • ICG – water soluble dye • Cleared from circuln by liver – Hepatocyte uptake, biliary excretion • IV inj.  ICG levels @ 5 min, 15 min • Measured as - ICGR15/ ICG-PDR/ICG - k • ICGR15 >14-20% - assctd with PHLF/complicns • Limitations – Not reliable in Hyper BR/ Intrahepatic shunting/ sinusoidal capillarization; • ICG – not remnant specific – only global liver function
  • 53. NUCLEAR IMAGING FOR LIVER FUNCTION MODALITY RATIONALE ADVANTAGE LIMITATION Tc99m-GSA(Galactosyl Serum Alb)(glycoprotein analogue) scintigraphy Binds to hepatocyte receptors CLD – reduced hepatocyte receptors plasma glycoprotein increased Provides anatomic and functional information ?Specific to remnant liver function if combined with SPECT High interrater interinstitution variability Limited availability No measure of regional liver function HBS with Tc99m Mebrofenin[IDA(Imino- diacetic Acid) derivative] Metabolized by liver correlates well with ICG Good marker of post resection liver function
  • 54. Other measures of metabolic function (lidocaine, galactose, 13C breath tests) Metabolized almost exclusively by the liver (P450) Poor clearance  liver dysfunction Correlated with other measures of total liver function Not widely available High interrater variability Time consuming Not specific to remnant Altered based on environmental conditions MRI with Gd-EOB-DTPA Contrast(50% excretion in N liver) Taken up and cleared by Hepatocytes Poor uptake  liver dysfunction Routinely available Assessment specific to remnant liver Not directly correlated with postresection clinical outcomes Galactose elimination test Accurately reflects metabolic function of the liver Altered based on envtl conditions US Transient elastography Provides assessment of liver fibrosis Noninvasive Fast User dependent Not correlated with clinical outcomes Gold standard remains volumetric-based assessment of the FLR with cross-sectional imaging (CT or MRI).
  • 55.
  • 56.
  • 57. • DRUG INDUCED CHOLESTASIS Bland cholestasis Anabolic steroids, some antiandrogens, OCPs, Azathioprine, cetirizine, glimepiride, infliximab, metolazone, tamoxifen, warfarin Inflammatory cholestasis Penicillins, Macrolides, Sulfonamides, Tetracyclines, Antivirals, TCAs, BZDPs, Antipsychotics Vanishing Bile duct syndrome Psychotropes, ABs, NSAIDs Sclerosing cholangitis Chemo(Floxuridine), Intralesional agents – Absolute Alcohol, HTS, Iodine
  • 58. ALF • Acute liver injury • Coagulopathy (iNR>/= 1.5) • Encephalopathy • Duration < 26 wks • No P/H/O liver disease • ETIOLOGY • Drug iduced • Acetaminophen – (dose>12g/d, but even at 3- 4g/d); intermediate NAPQI uses up glutathione • Centrilobular hepatocyte necrosis • Others • Antimicrobials MC ATT – Less favorable clinical response • VIRAL • HAV(3%), HBV(7%) – 10% of ALF • Others – • Indeterminate(12%), AI(7%), ischemic(6%) Wilsons(1%) HAV HBV Sptneous recovery 58% 24% OS 87% 69% Rx Supportive Antiviral
  • 59. ALF – MEDICAL MANAGEMENT Grad e I HE changes in behavior, Normal consciousness level Out of ICU set-up Grad e II HE disoriented, delayed mentation, asterixis ICU; GCS/Unresponsiveness score charting CT brain – R/O SDH b4 ICP monitor insertion Enteral/Parenteral nutrition; electrolytes Avoid sedation III In & out of consciousness, confusion ICP monitor(controversial), ETT, If ICP to be – INR < 1.5; ICP in place – INR< 3 CPP - > 60 mm Hg; 30 degree head elevation; If AKI with III/IV HE – vasopressin – MAP; Prophylactic HTS – Na – 145- 155 Increased ICT – Mannitol  Hypothermia Vasopressors – MAP - CPP Continuous veno-venous HD for AKI
  • 60. • UNOS 1A urgent waiting list pt • > 18 yrs • < 7 days’ life expectancy without LTx • Onset of HE within 8 weeks • No pre-existing liver disease • Currently underICU care • + One of : • Ventilator dependent, • Requires renal replacement therapy • INR > 2.0
  • 61. LIVER SUPPORT SYSTEMS • Features – • Free passage of toxins requiring breakdown • Free passage of newly synthesized proteins • Exclusion of the patient’s antibodies/complement components to prevent cytotoxic effects • Prevention of cells in the support system entering the patient’s circulation
  • 63. • Artificial Liver Support • Extracorporeal liver assist – No biological materials(hepatocytes/ cell lines) • Bio-Artificial Liver Support • Ideally – Human Hepatocytes; • Currently used - human hepatoblastoma cell • line HepG2/C3A; primary hepatocytes from pig livers.
  • 64. Plasma exchange/Hemodiafiltrn PE – exchange non cellular components from blood with FFPs HDF – Washes plasma in dialysate to detoxify Molecular Adsorbent Recirculating System(MARS) Albumin dialysis within 3 circuit system 70 kDa pore size membr Charcoal filter, resin binding column Albumin doesn’t pass Fractionated Plasma Separation & Absorption(Prometheus) Larger porosity membr – 200kDa; toxin-albumin complex passes the membrane – alb purified ELAD(Extracorporeal Liver Assist Device) HepG2/C3A cells Hemoperfusion from patient through columns containing C3A cells Has 2 acellular membranes – to prevent hepatoblastoma cell spill into patient blood HepatAssist 70g cryopreserved porcine hepatocytes Plasmapheresis activated charcoal  Oxygenation  Hepatocyte bioreactor
  • 65. • Drawbacks of ALS • No specific drawbacks • FULMAR Trial – RCT on MARS in ALF - no statistical significance in 6-mth & 1 yr OS • RELIEF Trial – RCT – MARS on ACLF – No significant survival benefit • MARS – No increased incidence of adverse events • HELIOS study – Prometheus in Acute decompensation in cirrhotic pts – No survival benefits – but subgroup analysis – MELD> 30 & HRS –type I – survival advantage • Drawbacks of BALS • Hep G2/C3A Migration into patient circulation(ELAD) • Zoonotic infections eg. Porcine Endogenous RetroVirus (PERV) • Isolated Primary hepatocytes(IPH) – lose function, undergo apoptosis under ex-vivo conditions ? • In 3D clusers, IPH don’t lose functions
  • 66. ISCHEMIC HEPATITIS • Shock liver/ Hypoxic liver injury • Hypoperfusion/systemic hypoxemia  extensive hepatocyte necrosis • Transient massive rise - serum aminotransferases, rapid decline after oxygen supply restored. • 79% - predisposing acute cardiac event; 23% - sepsis • Passive congestion of liver  elevated R- sided pressures increase sinusoidal pressure impedes flow from PV • Trauma; Hemorrhage; Sepsis; Acute cardiac Injury(Myocardial stunning) • Sepsis – reduce oxygen extraction, increase hepatocellular O2 use • Rx – improve hepatic perfusion by increasing intravascular volume/ Inotropes
  • 68. • Not precise enough to predict the requirement of intervention • A, B, C  additional injuries; monitoring response to resuscitation • Deciding factors - mechanism of injury(Blunt v/s Penetrating), hemodynamic instability(+/-), response to resuscitation • FAST – • Rapid imaging in hemodynamically stable/ unstable patients with possible hepatic injuries • 4 views of abdomen - cardiac (for pericardial effusion), R& L upper quadrants, suprapubic (presence of fluid). • Sn – 83%; Sp – 99% • FAST for blunt abdominal trauma with hypotension – Sn & Sp may increase to 100%. • HD unstable FAST - + No Extraperitoneal source/ Exploration Hemoperitoneum suspect Rpt FAST/DPL Stil –ve, but still hemopritoneum suspect Diag/Therapeutic exploration
  • 69. • CECT abdomen, pelvis – Most Sn, Sp imaging in Hepatobiliary trauma • If HD stable • Parenchymal lacerations/intrahepatic/ subcapsular hematoma +/- active extravasation of intravenous contrast • If CT worrisome for active IV contrast extravasation  repeated  active bleeding on venous phase • NOM – MC in blunt trauma pts - . 73% - NOM, with 7% - failure rate. • HD unstable/fail to respond to resuscitation/ hollow viscus injuries/peritonitis on exam  exploration • Grades I, II, III • Observe – Hb every 8 hrs for 24 hrs • Hb stable, diet Unstable/Transfusion+ • Discharge ICU/addl imaging/Sx
  • 70. • AAST Grade IV/V • SICU/Hb 6hrly for 24 hrs(NOM) • Need for BT/HD instability Successful • Repeat CT/Angioembolizn/Sx Interval CT • Bleeding parenchymal injuries - best managed by vessel ligation. • Direct suture ligation - preferable to Surgical clips • Penetrating liver trauma + uncontrolled hemorrhage Options – • Balloon occlusion of tract/Tractotomy/Angioembolizn after packing • Hepatorrhaphy – for venous bleed/Bile leak • Non absorbable suture, horiz. Mattress – to ctrl small bleeding cracks(after ctrl of major vessels & ducts)
  • 71. • Omental flap indications • Bleeding crevasses/post resection coverage of remaining surface/For larger area without liver capsule/Ruptured/surgically entered subcapsular hematoma with bleed
  • 72. Principles of Hepatic packing Choose the appropriate patient Control arterial bleeding by Sx / angioembolization Lesser venous bleeding/coagulopathy - Packing Timing - before excess bleeding/ coagulopathy develops Beware of acute traumatic coagulopathy Pack to compress liver in superior to inferior plane Anteroposterior packing – compresses IVC Count sponges when feasible - facilitates later removal Temporary abdominal closure - avoids tension/ secondary abdominal compartment syndrome Operative Techniques for Control of Liver Injury Cautery Argon beam coagulation Hemostatic adjuncts Individual vessel ligation Parenchymal reapproximation with large mattress sutures (Hepatorrhaphy) Selective hepatic artery ligation(SHAL) Resectional débridement Hepatic lobectomy (or major resection Omental packing Packing and planned reoperation
  • 73. Major HVI confined to liver parenchyma Sututre Ligation Bleed not readily apparent, collecting in deep crevasse Finger #, Tractotomy, localize  suture Avulsion of HV from VC Pack Fine vascular clamps to reapproximate anterior wall of VC & major HVs fenestrated endovascular stent grafts Historically – Cavo-Atrial shunting – ICD tube/ET tube through R atrium to IVC THVE – Pringle Suprehepatic Intrathoracic VC Suprarenal Infrahepatic VC DCS Perihepatic packing Avoid fascial closure(Prevent ACS) wait – 6 – 24 hrs Adjuncts of NOM Arterial blush Angioembolisation Hemobilia Angioembolisation Bile leaks ERCP, Sphincterotomy, stent Perihepatic collections Pigtail Large amt blood/bile/ascites  ACS D-lap (gasless system)  evacuation of major collections
  • 74. Special PROBLEMS IN LIVER INJURY • S.C HEMATOMA • Less likely delayed bleed than splenic S.C.H • Indication of intervention – rupture(Temporary packing/Omental flap); contd expansion/assctd arterial blush(Angioembolisation) • HEMOBILIA • Blunt liver trauma days to weeks  Melena, jaundice(clinical/subclinical) • IOC – Arteriography(CTA) TOC – Angioemb. • BILHEMIA – Fistula btw IHBR to Vein • Bile Blood – Jaundice • TOC – Angioemb +ERCP/Stenting • LIVER AVULSION • Venovenous bypass  Autotransplant of liver • GB INJURY  TOC - Cholecystectomy
  • 76. SIMPLE HEPATIC CYSTS • Origin – biliary tree – Microhamartomas/ peribiliary glands isolated from biliary ducts • Lining - Simple cuboidal epithelium • Contents – MC serous/ proteinaceous material from previous hemorrhage • Mucinous/ solid - implies infectious or neoplastic process. • MC in age > 40 yrs; F>M (some studies) • Symptoms –due to mass effect, liver capsule stretch; more in elderly • LFTs - N • USG – btw cyst/solid; Anechoic masses/smooth margins/thin walls/ Lack of septations • CT - nonenhancing/water density (0-10 U)/ smooth,thin walls – drawback – small lesions not characterized • MRI – Imaging of choice for newly discovered liver lesions; smaller lesions; homogenous hypoT1, hyperT2/Non-enhancing – Hemorrhage – hyper T1,T2; fluid-fluid level
  • 77. SIMPLE HEPATIC CYST • INTERVENTION – Symptoms/suspicion • Aspiration – 100% recurrence • Aspiration & sclerosant injection (if no bilious communication)– 20 – 80% recurrence • Cyst fenestration – lap/open – 1st aspirate – if bilious – look for communication – oversew • Lap v/s open – recurrence/morbidity - <10% • Resection – least recurrence, max morbidity • TOC – Lap fenestration – min morbidity, comparable recurrence
  • 78. POLYCYSTIC LIVER D/S • ADPKD/ADPLD • ADPKD – PKD1, PKD2 gene mutations ; ADPKD – predicts size of renal cysts, not liver • ADPLD – SEC63, PRKCSH genes • Prevalence – F>M, increases with age, exposure to pregnancy, hormonal Rx • Symptoms – mass effect, capsule stretch • Complications – 5% - cyst infection, PHT, ascites, variceal bleed, HVOO • Gigot et al classfn of PLD – CT scan based – guides Rx • Type 1: </= 10 cysts >10 cm/large uninvolved liver parenchyma. • Type 2: Diffuse liver involvement/ medium- sized cysts/large uninvolved liver parenchyma. • Type 3: Massive, diffuse liver involvement/ a few areas of normal liver parenchyma.
  • 79. POLYCYSTIC LIVER D/S • TREATMENT - if reduces hepatomegaly/long term relief • Medical – Immunotherapy – sirolimus/Somatostatin analogues – studies – palliative • Percut Transcatheter Hep A embolization - palliative • Aspiration & sclerosant – 30-100% recurrence • Sx – Fenestration(for type 1)MC complication – Ascites)/resection/LTx(for type 3- NO SURVIVAL ADVANTAGE).
  • 80. HYDATID DISEASE • E. granulosus (worldwide; unilocular, spherical)/multilocularis (metastatic d/s)/oligarthrus(peripheral ie skeletal muscles)/vogeli • Dvptl stages: adult tapeworm (sexual stage), cystic/ infiltrative larval metacestode (asexual) • Adult tapeworm – head/scolex, body/strobila, with three or four proglottids –The last proglottid - largest -have mature eggs - eggs have embryo/oncophere/hexcanth -3 pairs hooklets. • Cyst expansion – slow - < 1 cm diameter per year • Symptoms are unusual until cysts reach 10 cm
  • 81. HYDATID DISEASE • 3 layers: Germinal layer/Laminated layer/Advential layer. The • Central hydatid cavity with fluid Germinal – layer(Germinative membrane/living part)  Laminated layer. • Germinal + Laminated layers = Endocyst • Ectocyst/pericyst - fibrous layer(Compression of host tissue around endocyst). • Germinative layer - produces protoscolices
  • 82. HYDATID DISEASE • Adult tapeworm – in dog(MC definitive host) intestine – releases infected EGGS  dog feces soil/water/plants intermediate host, sheep (humans - accidental intermediate hosts) eggs hatch, embryo migrates through intestinal wall portal system. • Metacestodes (larval forms) - liver, lung, spleen, kidney, brain, bone – hydatid cyst with proctoscolices – ingested by dog • 80%- single organ involved.
  • 83. HYDATID DISEASE • Brood capsules – Invaginations into cyst cavity by undifferentiated cells in germinal layer – contain numerous proctoscolices • Germinal layer – secretes fluid/source of daughter cysts • Daughter cysts lack - adventitial layer . • Daughter cyst formation – by endogenous (MC)/exogenous vesiculation (leak in laminated layer – ‘satellite’ daughter cyst – 16-65%) • Ectocyst/Pericyst – host response - present in – liver, spleen; absent in – lung, brain • Uncomplicated cysts – sterile hydatid fluid • Bile-stained cyst fluid - cystobiliary communication. • Superadded infection – purulent fluid • Degenerated cyst – turbid fluid • MC site of liver involvement – R lobe; seg VII/VIII
  • 84. HYDATID DISEASE • COMPLICATIONS : • COMPRESSION – Compensatory HT(Adj liver); OJ(Bile duct); Budd Chiari – like(IVC/HV); Sinistral HT(Splenic V) • INFECTION – bacteremia/biiary communication • RUPTURE – 1. Bilary tract 2. Bronchial tree 3. Peritoneum 4. Other organs • Cysto-biliary communication(CBC) – MC complication • Minor(size < 5mm – reveal postop – bile leak); Major (5-10% incidence, size > 5mm)– OJ/Cholangitis • Incidence – symptomatic - 1 – 42%; total - 90% • Cyst size > 10 cm/near hilum/high pre-op GGT – high risk factors predictive of CBC • Major CBC – daughter cysts slip into biliary system (65%) – cholangitis; less in minor CBC • Diagnosis – US/CT – detached membranes, IHBRD/EHBRD; ERCP - Confirm obstruction • Rx – ERCP; sphincterotomy, extraction of debris with balloon
  • 85. HYDATID CYST D/S • BRONCHIAL RUPTURE (BBF) - Rare – MC in cysts in posterior, upper segments of the liver (IVa, VII, and VIII) • INTRAPERITONEAL RUPTURE – secondary hydatidosis; Spontaneous/trauma – 1-8% - silent/symptomatic/ acute abdomen +/-; anaphylaxis – 1% • Incidence of primary peritoneal hydatidosis – 2% • < 5 cm – usually asymptomatic • Abdominal pain; cholangitis; anaphylaxis(intraperitoneal rupture); bronchobiliary fistula • DIAGNOSIS – • Increased ALP, GGT – CBF • Increased TLC – infected cyst; Eosinophils > 3% - in 25-45% of pts • Serology – confirmatory - for D/D, Post Rx F/U, Epidemiological surveillance – MC used – Ab detection – IEP, Blotting, ELISA • False +ve – other helminth infn; low +vity in children • ELISA – Sn – 85-98% - IgM - -ve after 6 months of successful Rx; IgG - +ve for 4 yrs
  • 86. • RADIOLOGY – • CT and MRI - indications – • Subdiaphragmatic location • Disseminated disease • Extraabdominal location • Complicated cysts (abscess, CBF) • Presurgical evaluation. • MRI > CT – For characterization of lesion; higher Sn • US - first-line imaging -at both individual & population levels • WHO Classification, GHARBI Classification
  • 87. HYDATID CYST DISEASE – WHO CLASSIFICATION - USG Cyst type WHO Classification GHARBI Description CL (D/D needed) well-circumscribed liquid image with clearly defined wall – Early stage active, fertile cysts CE1 I Concentric hyperechoic halo around cyst; hydatid sand + – free floating active, fertile cysts CE2 III Multivesicular; daughter cysts; Rosette/honeycomb/spoked wheel/cluster active, fertile cysts CE3a, CE3b II Laminated layer detaches; undulating membranes; Water lilly/ water snake transitional, active or inactive cysts CE4 IV Solid & Liquid components; no daughter cysts Degenerated, inactive CE5 (Least typical of hydatid; D/D needed) V Amorphous mass; solid/ semisolid components; calcification in pericyst Partially/ totally calcified
  • 88. • CT/MRI - indications • If Sx Rx planned • subdiaphragmatic location • disseminated disease • extraabdominal location • Cysts close to hilum • Complicated cysts (abscess, cystobiliary fistulae) suspected • T2-weighted MRI - low signal intensity rim - characteristic sign of hydatic disease • Daughter cysts – T1 – hypo; T2 – hyper re;ative to cyst fld • MRI + MRCP - preoperative diagnosis of cystbiliary fistula (80% Sn, 100% Sp) • Intracystic fat density in MR – CBC
  • 89. HYDATID CYST TREAMENT • Goals – • Entire parasite removal • Residual cavity removal • Identification, treatment of biliary fistula • Modalities - • Radical surgery • Conservative Sx • PAIR • Benzimidazoles (BMZs)
  • 90. HYDATID CYST TREATMENT Modality Indications Contraindications Medical < 5 cm CE1, CE3a Peritoneal cysts Multiple cysts in > 2 organs Prevent recurrence following surgery or PAIR Pregnancy Uncomplicated CE4 and CE5 Alone if cyst > 10 cm Cysts at risk of rupture Chronic hepatic disease Bone marrow depression PAIR >5 cm; CE1, CE3a Inoperable/Refusal/Relapse/Failure to respond to Rx Biliary fistulae CE2 CE3b CE4 CE5 Surgery Large CE2-CE3b cysts with multiple daughter vesicles Single superficial liver cysts Complicated cysts(CBC, Infn, compression) General contraindications for surgery Uncomplicated CE4 and CE5 Very small cysts
  • 91. Sx • Avoid spillage; protection of peritoneal tissue & organs - protoscolicide-soaked surgical drapes, soft injection • Protoscolicides - 70% - 95% ethanol, 15% - 20% HTS, 0.5% cetrimide • At present - 20% HTS - recommended • Contact germinal layer - >/= 5 min; • Avoid in CBC – Chemical sclerosing cholangitis • Periop Albendazole(ABZ) – 1 day before – 3 mnths after Sx • Thoraco-abdominal incision only when simultaneous R lung & liver d/s – combined Sx • Lap v/s open – Chinese literature – results comparable; MC performed lap procedure – Cystectomy
  • 92. Conservative Sx • Cystectomy/ closed cystectomy/ cyst unroofing – simple, safe than radical Sx • No liver resection; • Risk – spillage, secondary hydatidosis – Highest in cystectomy • Steps – 2 layered packing – NS, HTS  punction aspiration injection (if no CBC) hydatidectomy (daughter cysts, laminated, germinal layers) unroofing (adventitia layer and thinned-out liver). • Min contact time with proctoscolicide (20% HTS) – 6 min) – Risk - Hypernatremia • CBC – IO Cholangiogram/GB compression/Transcystic methylene blue • Rx – MC – Suturing> RYHJ, Liver resection • Residual cavity – MC – Omentoplasty + DT; Capitonnage, capsulorrhaphy – not used • Post-op complications – • Biliary fistula (1-10%) – Sphincterotomy/ENBD/Combinations – 85- 100% success – closure in 2-4 wks • Biliary stricture  secondary cirrhosis – Sx not feasible – Long term endoscopic stenting safe
  • 93. Radical Surgery • Pericystectomy - radical cystectomy/capsulectomy/total pericystectomy/cystopericystectomy/pericyst ectomy –complete removal of the hydatid cyst. • Sx plane – just outside pericyst layer without opening the cyst • Plane – no difference from that of classical • Contraindication - cyst impinging on Hepatic V, IVC, liver hilum. • Liver resection – • The only surgical Rx for E. multilocularis; but too radical for E. granulosus • Other rare indications – • Atrophic remnant liver parenchyma, • Large bile leak untreatable Roux loop. • Peripherally placed cysts in left lateral segment • Pedunculated lesions
  • 94. • Recurrence – incidence – 10% • Predictive factors – Lap approach; cysts> 7 cm • H/O liver hydatid cysts, number of liver cysts, surgeon’s degree of practice • Close F/U @ 6 month intervals • +ve serological test during F/U – not s/o recurrence; Rising titre – s/o
  • 95. • PAIR – destruction of germinal layer • PAIR Catheterization - evacuation of enrire endocyst • PEVAC - percutaneous evacuation of cyst content • Risk - spillage of hydatid fluid during puncture • Prevention - US/ CT guidance, transhepatic approach to the cyst approach, • PAIR – Ben Amor et al. – • Indications for PAIR + MBZ/ABZ(Pre & post procedure) - large (>5 cm) CE1 & CE3a cysts. • Interval between injection of proctoscolicidal agent and Reaspiration – 15 min • Signs of involution - 3 mths heterogeneous reflections of cyst content 5 mths obliteration and pseudotumor appearance 9 mths loss of echogenicity, cyst disappearance
  • 96. • PAIR Catheterization – Akhan et al – • PAIR followed by catheter – iin situ for 24 hrs – if no Bile stain  cystogram to confirm • < 10 ml bile for 24 hrs – absolute alcohol injected (25-35% of cavity volume) 20 min  aspirate  withdraw catheter • > 10 ml bile for 24 hrs – catheter left in situ – till < 10 ml • PEVAC(Percut evac of cyst content) – Saremi, McNamara et al – • Aspiration  catheter left in situ  catheter replaced with 14 -18 Fr stiff sheath  suction catheter into cavity  cyst contents – evacuated by suction  Special cutting instrument - to fragment & evacuate daughter cysts, laminated membrane – Simultaneous scolicide irrigation • Catheter left in situ – remove > 24 hrs > 6 cm OR volume > 100 ml PAIR Catheterization < 6 cm OR volume < 100 ml PAIR
  • 97. • Benzimidazoles – MBZ & ABZ – • Kill by impairing glucose intake • ABZ better – better absorption in GIT, better results • 10 mg/kg BD with meals – NOT with antacid/H2 blockers/PPI • Alopecia – completely reversible; side effects – 1-10% • Single cysts – Rx Duration - 3 - 6 months. • Most relapses – within 2 yrs after treatment – but can occur 2 - 8 yrs • Efficacy of preoperative ABZ treatment – • Pre-op ABZ - 1 week before surgery. • Post-op treatment – 3 – 8 wks if no spillage; 3 -6 mths if spillage • ABZ - 10 - 15 mg/kg/day 2 doses • Fat rich meals - increase bioavailability. • Contiuous – No monthly treatment interruption • MBZ - 40 to 50 mg/kg/day, in 3 divided doses with fat rich meals
  • 98. • WAIT & WATCH - • Uncomplicated cysts (types CE4/ CE5). • CL cysts - not treated until diagnosis certain • ALVEOLAR ECHINOCOCCOSIS - • Metacestodes of E. multilocularis – infective form • Definitive & intermediate hosts – wild animals - exclusively in the liver - does not form cysts • Primary extrahepatic locations – rare • Infiltration/ metastasis – from liver to other organs
  • 99. ALVEOLAR ECHINOCOCCOSIS • Treatment • Radical surgery (R0 resection) - first choice if suitable • ABZ - mandatory in all - temporarily after complete resection of the lesions; for life - in all other cases; and (3) • Interventional procedures - preferred to palliative Sx.
  • 100. LIVER ABSCESS - PLA • ETIO-PATHOGENESIS • MC – Ascending biliary infection due to obstruction – East – stones; West – malignancy (cholangioCa) • GIT • Hematogenous spread – endocarditis, IV drug abuse • Trauma, TACE – necrosis – Secondary infn • BEA stricture – infn • Cryptogenic – 25% • Predisposing – DM, Cirrhosis • Presentation – initially non sp. Prodrome  later localize – RUQ pain, fever/chills, malaise(Triad); • MC symptom – Fever> RUQ pain • DIAGNOSIS – • Lab – TLC increase, Hypoalbuminemia, increased liver enzymes – Non specific • Radiology – • Chest X-Ray – elevated R hemidiaphragm/air- fld level in subdiaphragm. area, Pleural eff; Atelectasis – 50%
  • 101. LIVER ABSCESS - PLA • USG – Initial IOC – Sn – 83 – 95% • Assesses maturity of abscess – Hyperechoic, indistinct initially hypoechoic, distinct walled • IHBR, Hepatolithiasis, CBD calculi • CECT Abdomen – PLA v/s other liver lesions • Sn – 93-100% • Smallest size of liver abscesses detected – 0.5 cm • Micro v/s Macroabscess - < 2cm v/s > 2 cm
  • 102. LIVER ABSCESS - PLA • Microabscesses – Miliary v/s Clustered • PV phase - peripheral rim enhancement(hypodense cystic lesion + segmental wall enhancement, surrounding low-density edema) • Narrow Transition zone btw hypodensity & peripheral rim • MR – No sp. Advantage compd to CT • Indication – Diagnostic uncertainty even after CT abdomen • T1 – hypo, T2 – Hyper; MRCP – level of obstrn
  • 103. LIVER ABSCESS - PLA • MICROBIOLOGY • Pathogen isolation – Cavity > blood C/s • 33-55% of abscess cavity C/S – polymicrobial; less frequency of blood C/S polymicrobial • GP, GN, Anerobes • MC – E. coli, Strep,Enterococcus, Kleb • K. pneumoniae- (Asia> West) – Invasive K. pneumoniae liver abscess syndrome – Lungs, CNS, Eyes • K. pneumoniae in this – addl virulence factors – Capsular type K1, K2 Ag, magA, rmpA • MC isolated anerobes – Bacteroides> Strep milleri • Hematogenous spread – Staph aureus, Strep sp. – Solitary • GI spread – Polymicrobial, Aerobic GN, GNAnerobic • Gm staining – Sn Sp Gram + cocci 90 100 Gram –ve bacilli 52 94
  • 104. LIVER ABSCESS - PLA • TREATMENT – • ABs • Blood C/S, Abscess cavity aspirate C/S • Initially Broad spectrum AB • Biliary disorders - GNB, Pyeliphlebitis - GN & Anerobic • Extended-spectrum penicillins (piperacillin- tazobactam, ticarcillin-clavulanate, ampi- sulbactam), carbapenems, or 2nd gen ceph +/- metro • Started parenterally for 2 - 3 wks  convt to oral - complete 4-6-week course • DRAINAGE PROCEDURES - • PCA, PCD – Mainstay of Rx for PLA(1st line) • Multiple PCD/ multiple aspirations – effective • Rx underlying cause – MC – biliary obstruction/ communication • Predictors of failure of PCD - • Abscess C/S – yeast; Abscess cavity – biliary communication • If PCA/ PCD fails – Sx drainage/ liver resection
  • 105. LIVER ABSCESS - PLA • ENDOSCOPIC PROCEDURES – • EUS guided TG/TD plastic/metal stent/ catheter drainage • For PLA with communication with IHBD  ES + Nasobiliary drainage/ stent – removed > 4-6 wks • Median time for fistula closure – 6 days • LAP Rx of PLA & ASSCTD PATHOLOGY - Indicns • Failure of medical Rx & PCD • C.I to PCD • Septic shock needing emergency Sx • Surgically accessible lesion, minimal vasculobiliary injury risk • No previous major Sx in RUQ • No concomitant conditions requiring additional surgery • Shorter time to oral intake, LOS - in laparoscopic group (P <.05). • Video – Assisted Hepatic Abscess Drainage, VARD.
  • 106. LIVER ABSCESS -PLA • SURGICAL DRAINAGE • INDICATION • Failure of medical management • Failure of PCD • Complications secondary to PC treatments(bleeding/ spillage) of pus into the peritoneal cavity • Exploration - control of any associated intraabdominal pathology is performed. Localization of all abscesses (palpation liver & IOUS). • Needle aspiration to confirm location abscess & C/S & Gram stain. • The area of abscess isolated from abdomen with laparotomy sponges. • Suction  Suction drainage
  • 107. LIVER ABSCESS - PLA • HEPATIC RESECTION • Single/ multiple PLA is with severe hepatic destruction partial hepatectomy – best therapeutic option • Low mortality rate • Underlying malignancies who require hepatectomy for liver destruction secondary to PLA poor outcomes • Worldwide – 3-30% • INCIDENCE OF MALIGNANCY IN PLA • Incidence of GI cancer was 4.3 times higher in patients with PLA • PLA pts - highest incidence of colorectal cancer > biliary tract > pancreas > small intestine
  • 108. LIVER ABSCESS - ALA • E. hystolytica(invasive form) • Majority – asymptomatic • Liver – MC extraintestinal site – Hepatic abscess - 3-9% incidence in amebiasis • R/F – • Male (though intestinal amebiasis – M=F) – Alcohol/Menstruation/hormonal • 4th – 5th decade; Poor health & sanitation • Immunocompromised – HIV • LIFE CYCLE • Trophozoites – shortlived outside; Cysts – days – wks outside human body • Resistant to gastric pH, excystation in alk pH – R colon (MC affected intestinal amebiasis) – PV radicle – R lobe liver • Anchovy paste – sterile usually – dead PMN + dead hepatocytes • IMMUNOPATHOLOGY – • Early stage – PMN surrounding trophozoites • Later – 3 days – Lymphocytes, Macrophages, Epithiloid cells – Granuloma formn
  • 109.
  • 110.
  • 111. • CLINICAL PRESENTATION • Amebiasis – MC asymptomatic • ALA MC symptom – High grade Fever, RUQ pain/ ?previous dysentery • Pleuritic & right scapular pain - if the diaphragmatic surface of the liver – involved • Young males - tender, solitary, R-lobe abscess. • Amebic serology titers > 1 : 256 IU • Jaundice – uncommon – Compression >> fistulization • LAB INVESTIGATIONS • Amebiasis/ dysentery – First step – Feces Light MS • Trophozoites in feces/submucosal biopsies • 3 stool specimen – different days over 10 days • Charcot leyden crystals & blood - acute stage • Fecal occult blood • Diagnosis of ALA - confirmed by +ve serology Sn -> 94% & highly Sp >95%. • False neg – in 7th – 10th day • Ab detection - IHA, LA, CIE, • Amebic gel diffusion test, immunodiffusion, CFT, IFA, ELISA – ELISA MC
  • 112. • Serology +vity – endemic v/s non endemic area (acute infn) • PCR – IOC for clinical/ epidemiologic studies – In West - feces, tissues, abscess aspirate. • IMAGING • CXR – 50% shows changes • USG – Hypoechoic well defined; round edges – 90% diagnostic accuracy; guided aspn • CT – Imaging study of choice – solid lesions D/D; Guided aspn • ALA V/S PLA – less clear • Radiological resolution – 3 – 9 mths to yrs • SITES – • Liver>> Brain(CT – irregular lesions – no capsule/enhancement) • Intestine – ameboma(mimic Colon Ca; GI bleed, Rectovag fistula) ALA PLA Sero titres Amebic sero> 1:256 < 1:256 Albumin Less severe Severe HypoAlbuminemia Liver enzyme(no value) Less elevated More elevated ALT, ALP
  • 113. LA in children • PLA >> ALA(Rare) • Rx – Amebicides (Metronidazole); No indication for aspn if uncomplicated • Porraz Ramirez criteria – Per cut. Aspn of ALA • No clinical improvement • Abscess diameter > 6 cm • Sepsis • Imminent rupture • Sharma criteria – Both ALA & PLA – Indications for PCD Sx drainage Large volume, high risk rupture Failed PCD Rupture already happened Pts on steroids E/O Liver failure Addl mgmt. of underlying abdominal problem Lack of response to med Rx ascites
  • 114. ALA - Rx • MEDICAL • Predictors • PCD, Sx Drainage • Indication for aspn • Age 55 years or • Old age, >/= 5 cm, Bilobar involvement, > 7 days Class Prototype dose Features Nitroimidazoles Metro 750 mg IV/oral TDS 7 – 10 d High tissue diffusion, cross abscess wall Dehydroemetine paromomycin,(DOC) diloxanide furoate; and iodoquinol
  • 115. Rx of ALA Drug treatment Uncomplicated ALA Both amebic colitis and LA— nitroimidazole derivatives (e.g., metronidazole) Amebic colitis—luminal agents - paromomycin, diloxanide furoate, iodoquinol PCD Deterioration in clinical condition despite adequate treatment Sx Ruptured abscess Impending rupture Inadequate catheter drainage
  • 116. • BILIARY COMMUNICATION – • OJ, Longer duration, larger abscess • ERCP Sphincterotomy – CBD Stent/ NBS • COMPLICATIONS • Rupture – into chest, abdomen • R/F – L lobe; 5-10 cm size • MC – peritoneum – 20-70% > pericarditis (30% mortality) • HV & IVC thrombosis. • Bacterial superinfection/ anemia/ARDS/sepsis • R/F for poor outcome for ALA • BR>3.5 mg/Dl • Encephalopathy • Hypoalbuminemia <2.0 g/dL • Multiple abscess cavities • Abscess volume> 500 mL/ anemia/ DM • Liver resection in LA • Infected hepatic malignant neoplasm, • Hepatolithiasis • Intrahepatic biliary stricture
  • 117. Hemangioma • MC; 70% of solid benign liver Trs. • F:M = 5:1; Middle age • > 10 cm = Giant hemangioma • Mostly solitary; 40% Multiple(same lobe) • Compressible/capsule • Endothelial cells/fibrous septa - cavernous vasc. spaces lined endothelium by connective tissue • B.S - Hepatic A/lack biliary or portal structures. • Endothilium – Vasc. Diffntn; Not portal • MC asymptomatic; incidental – at Sx/imaging • Symptomatic - giant hemangiomas - abdominal pain. • Mass effects - size, early satiety/biliary stasis/vasc obstn. • Complication – Rupture/Inflammatory reaction/ Kasabach Meritt syndrome (Intravasc coagulation, clotting, fibrinolysis  systemic DIC Uncontrolled bleed - 30-40% mortality Reversible by Sx removal)
  • 118. Hemangioma • Etiology – Congenital vasc. Malformn/Hamartoma – Growth is by Ectasia/ No e/o Hormonal etiology • Diagnosis – • USG – Hyperechoic/acoustic enhancement/Sharp margins; if large – heteroechoic • CEUS/CECT - rapid peripheral nodular enhancement (arterial phase) F/B centripetal filling • IOC – MRI – T1 hypo, T2 strong hyper/DWMRI – High apparent diffusion coefficient • Others – SPECT/Tc 99m scan/Hep Angiogram • Hepatic Angiogram - COTTONWOOL app. - large feeding vessel – displacement, pooling of IV contrast. • No Percut Bx – low yield/Risk of bleed • Treatment – Asymptomatic, estd diagnosis – No intervention • Indications for Intervention –Diagnosis uncertain/symptoms/inflammatory reaction/Kasabach-Merritt syndrome/rupture • Standard liver resection preferred to enucleation • LTx – Giant Hemangioma (difficult resection)/associated Glycogen storage d/s
  • 119. HEMANGIOMA – T2, T1, A, PV, Delayed phases
  • 120. Hemangioma • Medically Unfit for Sx/Technical reasons – Arterial embolization/ RT • Kasabach Meritt – Gold standard is resection – pre-op FFPs
  • 121. FOCAL NODULAR HYPERPLASIA • 2nd MC Benign hepatic neoplasm; • F:M = 8:1 • usually < 5 cm, 80% - Solitary. Only 3% >10 cm • Macroscopy - Lacks a capsule • Central scar around arterial vessel with fibrous septa radiating outward. • Microscopy - Normal hepatocytes arranged in thickened plates. • Kupffer cells +, hepatocyte-derived • biliary ductules, nodules + • No bile ducts bile • MC asymptomatic, incidental diagnosis • If symptomatic – compression/torsion • Rupture – rare • Malignant transform – not documented • Etiology - hyperplastic, regenerative response to malformed arterial structures • Associations – hepatic hemangioma, hereditary hemorrhagic telangiectasia (Osler- Weber-Rendu disease) • Genes involved – deregulation of vascular remodeling • Female hormonals & OCPs – not proven
  • 122. FOCAL NODULAR HYPERPLASIA • Pre-contrast – lesion - same US echogenicity/ CT attenuation/ MRI signal intensity as the surrounding liver tissue • Arterial phase - strong homogeneous enhancement with central vascular supply, & sparing of central scar • Portal,delayed phases – Contrast fades, lesion similar to surrounding liver • MRI – Precontrast – T1 – lesion – ISO/HYPO; • T2 – ISO/HYPER; Central scar – Strong HYPER • Superparamagnetic iron oxide (SPIO) contrast uptake – by Kupffer in FNH – differentiate from adenoma on MRI. • Scintigraphy with technetium 99m– sulfur colloid – Due to Kupffer • Angiography demonstrates a “spoked wheel appearance • Bx – in diagnostic uncertainty – low yield • Management – Asympt – No Rx/No stopping OCPs/Pregnancy • If sympt – resection – lap/open • Pedunculated lesions – Risk of torsion - Sx
  • 123. HCA • Rarer type • Young women - childbearing age • long-term - OCPs - 30-fold HCA increase • Newer low-dose estrogen +/- progesterone formulations- reduction in HCA • Multiple adenomas – in 30% pts • Adenomatosis – Multiple HCAs in all liver segments – No relation to hormones; associated with Glycogen storage d/s (Type Ia glycogenosis) • Types of HCA – Inflammatory(Telangiectatic)vHNF-1A mutn, Beta Catenin mutn; Unclassified • MACRPSCOPIC – Well circumscribed; pseudocapsule; C.S – Heterogenous, yellow brown, H’ge, necrosis
  • 124. • MICROSCOPY – Hepatocyte cords sepd by sinusoids; No KC or ductules • PRESENTATION – MC – Asympt, incidental; MC symptom – Abd. Pain; 1/3rd of IHCA pts – inflammatory syndrome + fever • MC Complication – bleed – 25% - sudden pain, shock; > Malignant transform(4-5% risk) • ETIOLOGY – Hormonal – OCPs(Dose dependent),pregnancy enlargement; androgen preparations, illicit androgen use by bodybuilders, NASH, GSD I, III, Obesity/metabolic syndrome R/F for bleed R/F for malignancy large tumors (>5 cm) Large Trs > 5 cm lesional arteries male gender (6- to 10-fold increased risk) IHCA subtype Beta catenin subtype L Lateral location of Tr Androgen use Exophytic growth
  • 125. • RADIOLOGY • USG - variable echogenicity; often hyperechoic (high lipid content) • Internal hemorrhage - cystic areas, +/- calcification • Intratumoral veins - on Doppler • CEUS arterial phase, - diffuse/ centripetal hypervascular enhancement from dysmorphic arteries. • PV phase -showing equal enhancement/soft washout relative to the liver • CECT Abdomen – • Appearance overlaps with FNH & HCC. • Plain CT - Similar attenuation to normal liver • A phase – • homogeneous enhancement, sharply marginated hypervascularity • Capsulated appearance(30%) • PV phase – fade. • Larger adenomas - more heterogeneous than smaller lesion(Hemorrhage)
  • 126. MR IMAGING FEATURES – HCA Type of HCA T1 T2 A PHASE Dynamic phase Delayed HB phase Inflammatory (30- 50%) Sn-87-91; Sp- 91-100 Hypo Strong Hyper – diffuse/rim- like(atoll sign) Moderate enhance Persistent enhance Variable uptake HNF – 1A(30-35%) Exclusive women Sn- 85-88%, Sp-88- 100%) Slightly hyper (Homogenous) Iso/hypo (varying) Less avid enhance than inflammatory Low uptake Homogenous low uptake Beta Catenin type(10-15%) – GSD, Androgen, male – almost HCC like Hypo/hetero Hyper/hetero Moderate/hetero enhance variable variable Unclassified (10%) – Almost HCC like No specific imaging characteristics
  • 127. IHCA – Plain T2, A, Delayed V
  • 128. HNF-1A HCA – T2; T1, A, PV, Delayed
  • 129. TREATMENT OF HCA • HCA • Male Female • • Resect < 5 cm > 5 cm • HNF1A Others • F/U Resect • F/U – 5 yrs > cessation of HRT/OCPs – Annual MR(Non IHCA)/ Bi-annual MR(IHCA subtype) • LTx – sympt. Unresectable HCA/ Adenomatosis/assctd GSD • Risk of complicns in adenomatosis(mostly HNF-1A type) v/s solitary adenoma – same • HCC< 5 cm with no bleeding – no need to discourage pregnancy
  • 130. Benign Hepatic Neoplasms Prevalence 3 – 20% HEMANGIOMA 1% FNH < 0.05% HCA Pathogenesis Vascular malforn/Hamartoma - congenital Hereditary; Hyperplastic response to vasc. malformn Sex Hormones/NASH/Glycogen storage d/s I, III AFP Normal Normal Normal Gross appearance Compressible/well ademarcated/Pseudocapsule (blood-filled “cyst”) No capsule/Brown, lobulated/central scar Pseudocapsule/ yellow-brown lipid/H’ge/Necrosis/Calcifn Microscopy Cavernous vascular spaces/endothelial lining/no bilio- portal str. Normal hepatocytes in thick plates/Kupffer cells, hepatocyte- derived biliary ductules – no bile duct Lipid/Gycogen rich Hepatocytes in plates; sepd. By sinusoids – Arterial perfusion Complications Mass effect, inflammatory reaction, Kasabach- Merritt syndrome Mass effecr/torsion if pedunculated Malignant Transformation N N Y, Male/Androgen/b-HCA, Tr diameter > 5 cm Rx Sx if sympt - enucleation/resect; Unresectable – LTx/embolisation Sx if sympt/Pedunculated; Hormonal Rx cessation – Not needed Sx – size, gender, subtype Hormonal Rx cessation - needed
  • 131. • Angiomyolipomas - mesenchymal tumors from perivascular epithelioid cells • MC in kidey; also appear in liver • Associated with tuberous sclerosis • MC in women between 30 and 50 years of age. • MC – asymptomatic, incidental diagnosis – less accurate • Inconsistent appearance(varying content - smooth muscle cells, adipose tissue, and blood vessels) • Liver biopsy often needed • Asympt, size < 5 cm  Surveillance with serial imaging • Size > 5cm – resect(Malignant transform risk) • IPL(Infl. Pseudotumor of Liver) • Benign, mimic cholangio Ca • Fibroblastic proliferation with PMN infiltration • Fever, abd. Pain, LOW, Jaundice • Imaging – challenging diagnosis • D/D – Cholangio Ca/AI cholangiopathy/ PSC
  • 132. • BILIARY HAMARTOMA (von Meyenburg complex) • Benign tumors – with disorganized bile ducts, ductules with fibrocollagenous stroma • Size - range from 1 to 15 mm; no biliary tree communication • Scattered throughout the liver • MC multiple, may be solitary • Nonspecific imaging appearance • T2-weighted MR images - multiple small strongly hyperintense lesions • D/D – cysts/metastases or microabscesses • No treatment needed • PELIOSIS • Multiple small blood filled pools in liver parenchyma – various sizes • Due to focal rupture of sinusoidal walls • Post Oxaliplatin chemo for CRLM; Anabolic steroids, OCPs, HIV, severe TB • Strong hyper T2-weighted MRI, anarterial phase enhancement in CT/MR • Usually – asymptomatic – rarely – rupture, bleed • Rx – withdrawal of causative agent
  • 133. • NODULAR REGENERATIVE HYPERPLASIA • Benign, diffuse, micronodular transformation of liver with hyperplastic hepatocytes • Primary vascular process  PV obliteration  ischemia, central zone hepatocyte atrophy proliferation of hepatocytes • Preneoplastic theory (Assctd HCC, Neoplasia) • 2% prevalence • Assctd with systemic d/s, drugs, steroids • Incidence in oxaliplatin-based chemotherapy for CRLM - 24% • Usu. Asymptomatic, clinically preserved Liver fn; occasionally PHT features – bleed • APRI score – AST: Plt Ratio Index >0.36, Plt < 1 L in CRLM chemotherapy pts – predictive of NRH • MR – T1 – hyper; T2 – Iso/hypo to liver • No central scarring • If imaging –ve PC Needle Open Bx • Rx – Asympt – No Rx; In Oxaliplatin chemo for CRLM, Bevacizumab reduces NRH incidence • Manage PHT • If NRH +  Avoid major resection OR do PVE
  • 134. • MC liver d/s assctd with FNH Like Lesions – • BCS • HHT • Congenital Hepatic Fibrosis • PV Cavernomatous transform
  • 135. HCC • R/F • VIRAL – HBV/HCV • Heavy alcohol, smoking – Independent & synergistic • Aflatoxin B1 • T2DM – increase risk in HCV pts • Coffee intake reduces risk • Cirrhosis underlies HCC in - 90% of cases • MCC of death in Cirrhotics - HCC • NAFLD/NASH - increased risk • GENETIC INFLUENCE IN HCC • Chronic hepatitis  Persistent inflammation HCC • Maintained injury --> repair with high proliferation rate  increase DNA mutn • HBV – Genetic damage by – inflammation + integration (genetic &epigenetic) into host DNA • HBV – Genetic damage –even without much liver insult –(cirrhosis) • HCV – Chronic inflammation
  • 136. FLHCC • Well demarcated, encapsulated, +/- central fibrotic area • Longterm survival – 50-75%; recurrence – 80% • Lymph node mets – worse outcome • LN mets & mets – Rx – resection • Gain in Protein kinase A activity – genetic basis for FLHCC • nonelevated AFP with large tumor, normal liver. • Plasma neurotensin levels, vit B12 binding capacity - increased
  • 137. PATHOLOGICAL VARIANTS OF HCC Mixed Hepatocellular-Cholangiocellular Tr Prognosis – better than HCC, worse than IHCC Clear cell HCC Resemble RCC Better prognosis than std HCC – controversial Pleiomorphic/Giant Cell Variant Origin – primary hepatic cells Sarcomatoid HCC/Carcino-Sarcoma Higher incidence of mets; No AFP Childhood HCC 25% of pediatric liver tumors Rare in infancy Viral Hepatitis, metabolic causes of liver cirrhosis Longterm survival 10-20% -higher multifocal, vasc. Invasion, extrahepatic mets Resection
  • 138. • Preventable R/F – • Preventn of viral infn – Vaccn HBV, Prevent blood transmissn of HCV • Alcohol intake • Aflatoxin contaminatn • Obesity  NASH • Decrease in viral replication  reduce HCC incidence • Antiviral therapy – SVR in HCV pts  cirrhosis/fibrosis regression • SVR  Reduced HCC risk • SCREENING FOR HCC • Abdominal US 6 mthly for cirrhotics – if HCC in them is treatable • AFP – NOT RECOMMENDED – Suboptimal accuracy - cholangiocarcinoma, Ca stomach, Liver mets – may produce AFP • Contraindication – LTx candidates with advanced liver d/s < 1 cm, Cirrhotic Not Malignancy in 60% Close F/U > 1 cm, Cirrhotic Characteristic AHE + Venous washout Single imaging enough to diagnose HCC No AHE + Washout FN Bx
  • 139. • Preop biopsy – not reqd for diagnosis – Risk of Tumor spillage(1%), H’ge • Mets – MC – Lung, bone, peritoneum • Chest CT – Mandatory, bone scan – only if symptoms • Staging Lap – indications – • Clinically apparent cirrhosis • Radiologic evidence of vascular invasion • Bilobar tumors • STAGING SYSTEMS – • CUPI – Population specific system • CLIP • Okuda
  • 140. • Non-Cirrhotic liver – Diagnosis of lesion of any size – by Histology • PIVKA, Glypican 3, AFP fractions • Bx – Not 100% Sn - -ve Bx – doesn’t R/O HCC • STAGING, PROGNOSIS • Prognosis – Tr stage at diagnosis, underlying liver status • Staging & Prognostic systems – • Recognize end-stage d/s • Not universally reproducible • BCLC – Tr burden; Liver Function; Ca related symptoms • 4 stages • Each stage - its own prognosis prediction, appropriate treatment strategy
  • 141.
  • 142.
  • 143.
  • 144. • Multiple satellite lesions in HCC develop due to involvement of • A. Portal V • B. Hepatic A • C. Hepatic Venules • D. Intrahepatic lymphatics • Ans? • Portal Vein
  • 146. RADIOLOGY - USG • For Surveillence – Sn – 60 – 90%; 6 monthly better than annual; • USG screened Cirrhotics – improved median survival & OS – in CHILD B, not in CHILD C • Small HCC tumors (< 5 cm) - hypoechoic OR hyperechoic(fatty metamorphosis) • Larger HCC – heterogeneous(liquefaction necrosis, fibrosis). • Sonographic depiction of HCC - limited in severe cirrhosis • HCC – PV/ HV thrombosis • Tumor v/s Bland thrombus – • CEUS – best characterize lesion > 2 cm • AHE, PV washout – typical feature • 22% HCCs – delayed venous washout • FLHCC – variable echo; Calcification, central scar,(30-60% pts) LAP Tumor thrombi Bland thrombi Expand PV Expand PV Spectral Doppler – Hepatofugal Arterial flow Spectral Doppler - Noise
  • 147.
  • 148. RADIOLOGY – CECT • HCC Diagnosis in CECT – difficult in cirrhotic livers • Enhancing PV Tumor thrombus – high Sp for HCC in cirrhotic liver
  • 149. LIRADS – DEFINITELY HCC CRITERIA EITHER OF Major features Enhancing tumor + in PV Washout appearance, -Diameter >/= 1 cm, < 2 cm - Hypervascular - At least 2/3 major features, Enhancing Tr capsule -Diameter >/= 2 cm -Hypervascular, - At least 1/3 major features Threshold growth(Dia increase >/= 50% in < 6 mths >/= 100% in > 6 mths New lesion > 1 cm • FLHCC • Unenhanced CT - hypoattenuating large solitary mass , welldefined margins • Central scar. • Calcification (Differentiate from FNH) – in 35% to 55% of tumors • A, PV phases - Nonscar portion of tumor – heterogeneous enhance • (FNH - homogeneous arterial enhancement around central scar) • Delayed phase - increasing homogeneity, occasional scar enhancement • Pseudocapsule - liver surrounding the mass • may be compressed • Vascular invasion/lymphadenopathy/Lung/peritoneal mets
  • 150.
  • 151. RADIOLOGY HCC - MRI • Hypo T1, hyper T2-weighted images • APHE, Delayed Phase WashOut(DPWO) • Signal intensity may be variable for < 2 cm HCCs • Large HCCs – T2 phase – mosaic pattern(Tr necrosis) • Intracellular lipid - important clue to small • DPWO – Sp only for Mod/Poor diff HCCs • Well diff HCCs – may not show DPWO • Peri-tumoral capsule – enhanced in delayed phase • FLHCC • Central scar – T1 & T2 - low signal intensity(FNH – Central scar - high T2)
  • 152.
  • 153.
  • 154.
  • 156.
  • 157.
  • 158. • BCLC Stage wise survival • Treatment Stage Migration • BCLC Assessment prior to Rx • Backgrund liver function – CTP scoring • Tumor characteristics – Satellite nodules, PVT, Extrahepatic spread, Vascular invasion • Extrahepatic spread – CT Chest, Bone scan • If expected LTx wait period > 6 mths – Percutaneous Rx • RFA/MWA; PEI (Subcapsular Tr, GB/ Heart near Tr) • Ablation best results – Size < 2 cm – recurrence rates = resection EARLY (A) 5 yr – 50-70% INTERMEDI ATE(B) 3 yr – 66% ADVANCED (C) < 1 yr
  • 159. • More advanced (unresectable/large/multifocal HCC) , NO PV invasion  TACE (if liver function preserved + Good PS) • If chemoembolization not feasible but preserved liver function (CTP class A or B) + Good PS - , OR advanced stage sorafenib
  • 160. IMAGE GUIDED ABLATION - HCC • Indication – early HCC • Single tumor <5 cm OR </= 3 nodules < 3 cm—when Sx precluded • Very early stage Trs (</= 2 cm) • Limited unresectable hepatic mets (esp CRLM) • Global Ablation Margin(A0) – Tr free margin 5-10 mm •
  • 161. Method Crux Advantages Disadvantages RFA -Highfrequency (375-480 kHz) A/C -Target cell death – Frictional heating -USG/CT guided High rates of local control </= 3 cm Tr Estd safety profile Known limitations Experience in combination Rx (HCC) Widely available High incomplete ablation rates in >3 cm Tr Heat-sink effect (“heat sumping”) - perivascular tumors(vessel>3mm) Thermal injury risk to critical str. Variability in RFA devices MWA -EM wave radn from probe Excite water within soft tissue “broadcast” at freq 900 - 2450 MHz -2 cm tissue sphere around probe Ablate Trs 3-5 cm dia in 5-8 min Less impacted by heat-sink effect Can activate multiple probes at same time No grounding pads required Efficacy data, safety data - limited Thermal injury risk to critical str (and vessels?) Variability in devices Cryo 17 gauge Ar cryoprobes/Liquid N2 Target tissue phase change Therapeutic iceball formnCell lethal isotherm (- 30 to -40 degree) Can activate multiple probes at the same time Can image the ice-ball formation Insufficient clinical data Risk of bleeding Risk of cryoshock IRE nonthermal ablation mS D/C current pulses Btw parallel monopolar probes within the Tr. Rx Trs near critical str( spares collagen/ conn. Tissue str) Heat-sink effect not relevant Insufficient clinical data Neuromuscular blockage, cardiac gating reqd
  • 162. • Local Recurrence after RFA – factors • Tr size > 5 cm • Tr Close to major vessel • Subcapsular Tr location • Intentional margin < 1 cm • Lack of vascular occlusion • Physician experience • Complications • IRE. • MWA - bleeding, bile leak, liver abscess, PVT • RFA • Other Ablation techniques • HIFU - Thermal ablation Rx – Acoustic energy  convtd to heat coag necrosis • Adv – No BV injury (No direct dependence on thermal energy) • Tr locn -< 1 cm from IVC, PV, or a main HV • PEI – Absolute alcohol/Acetic A – Coag necrosis- Lowest cost • Complete radio-response – 100% if Tr < 2 cm • Indications - • Smaller HCCs not amenable to RFA ( near major vascular structures/GB/Hilum)
  • 163. METHOD OF ABLATION COMPLICATIONS MWA Bleed, Bile leak, LA, PVT RFA Bleed, Bile leak/Stricture, LA, pleural effusion, pneumothorax, hypoxemia during treatment, S.C hematoma IRE PVT, pneumothorax, biliary occlusion, arrhythmias Cryo Bleed, biliary injury, LA, liver shearing,,“cryoshock.”
  • 164. HAE, TACE • Only 20% to 30% HCCs - candidates for curative Sx(resection, LTx) • Recurrence > curative resection - 50% - 70% at 5 years • Principles – • 90% to 100% of liver Tr BS – Hepatic A • Selective HAE  selective ischemic damage to Tr, spares normal liver (PV) • Hepatic Drug exposure if given through HA compd to systemic V - • Max for 5-FU(10*)>Mitomycin C(8*)>Cisplatin(7*)> Doxo(2*) systemic V admn • Tr stage/type • Encapsulated nodular HCC(HA) v/s well difftd Extracapsular infiltrating advanced HCC(PV/PV+HA) • Mets – whe < 200um – sinusoidal blood); midway – arterialized; but even if advanced – distinct PV supply.
  • 165. • Targeted tumor ischemia(embolization) + intraarterial chemotherapy • MC used – doxorubicin • Mixed in water/ water soluble contrast  mixed with lipiodol; • Water in oil type emulsion
  • 166. • Excess Lipiodol - flow back into PV via arterio- portal communication (“plastic” nature adjusts to microvessels size) • Transient arterial and • Portal embolization of HCC  Rx extracapsular infiltrative Trs, satellite nodules(perfused via portal venules). • Lipiodol – retained 6-12 wks in Tr cells only(Absent Kupfer cells) • F/B Lipiodol infusion HAE • Optimal size of embolizing material – small to occlude terminal Arterioles v
  • 167. • Embolising Agents – • A-P shunts – more in large Trs – embolise before TACE • INDICATIONS • MC – Unresectable HCC • Preserved liver function (Child-Pugh A or B7, PS(ECOG 0/ 1). • 1st line Rx - BCLC intermediate stage HCC (multinodular/asymptomatic Trs, no vascular Invasion/extrahepatic spread) • Alt Rx with curative intent – early stage HCC not fit for resection/ ablation(comorbidities/ anatomic problems)
  • 168. • CONTRAINDICATIONS – • CPS >/= B8 • Extensive Tr - massive replacement of both lobes of the liver • Major PV thrombus • Active UGI bleed/Refractory ascites/HE • Renal insufficiency/Anaphylaxis to contrast/severe PVD/Uncorrectable coagulopathy • INDICATIONS • Spontaneous rupture of HCC – Emergency TACE regardless of underlying liver function. • Nodular HCC showing exophytic growth – even in advanced cirrhosis TACE to prevent tumor rupture • Hypervascular metastatic lLiver Trs – NETs, GISTs, uveal melanoma
  • 169. • Doxorubicin dose - 20 to 75 mg – max 150 mg. • Lipiodol upper limit - 15 mL. • End points for emulsion administration - stasis in tumor-feeding arteries +/- Lipiodol appearance in PV branches • Therapeutic efficacy – • Tr necrosis extent - 60% to 100%. • Mean necrosis – selective TACE (75%)> Lobar TACE(52%) • 2-year survival of TACE in HCC > conservative management • TACE - benefit in 2 yr survival +; absent in HAE. • TACE as neoadjuvant Rx before liver resectn– No improvement - reduces resectability; increases operating time. • TACE as bridge before LTx - drop-out rate due to tumor progression – lower(3.0 - 9.3%) if mean waiting time on LTx list > 6 months • MS-GEP-NET – TACE as first-line Rx - 70% complete sympt. Response, 20% partial response. 5yr & 10 yr survival rate - 83% & 56% if used as first line Rx
  • 170. COMPLICATIONS - TACE • 4% • R/F – • Major PV obstruction • Compromised FLR • Biliary obstruction • Previous biliary Sx • Excessive Lipiodol use • Nonselective embolization • PES – Post Embolization syndrome • 60% - 80% of pts • Pain, fever, nausea, vomiting • Type of tumor lysis syndrome - Abrupt tr cell death by ischemic damage  intracellular toxins into circulation • Transient, non specific • Antiemetics, analgesics, and antipyretics. • ALF – 20%(3%- IRREVERSIBLE) • Liver Abscess – rare – 0.5 – 2% • Prior BEA/SOD – R/F
  • 171. • BDI – • Peribiliary plexus – from hepatic A. • 2% - 12.5% • Manifestation - intrahepatic biloma, focal stricture of CBD, diffuse dilation of IHBR • MC in - Mets, noncirrhotic liver, and in selective embolizn of distal hepatic A • NTE(Non Target Embolizn) – MC – GB • Skin – Int mammary A, Intercostall A • Gastroduodenal ulcers – LGA, RGA • Pulm. Complicns – Inf phrenic A • IATROGENIC VASC. COMPLICNS – • Coeliac, CHA - dissection
  • 172. • BLAND EMBOLIZN – MICROSPHERES • Equivalent effect as TACE in Rx of hypervascular Liver primaries & Mets • Inert elastic polymer with hydrophilic surface • tris-acyl gelatin microspheres (Embosphere); spherical PVA; Bead Block; polyphosphazene coated polymethylmethacrylate microspheres (Embozene) • DEB- TACE • DEB – release drugs at target tissue for extended time • 2 types of DEB - PVA based Microspheres, Superabsorbant polymer(SAP)[Hepsph./Quadrasph.] • PVA – 100 – 900 um hydrogel microsph. • Objective response - DEB-TACE (51%) >cTACE group(44%) • Objective response margin DEB TACE V/S c TACE – Higher in – • Child-Pugh class B, ECOG 1, bilobar/ recurrent d/s • DEB – Better tolerability, Reduced liver toxicity • No diff in TTP, OS
  • 173. RADIOEMBOLIZATION • Nolan & Grady – First studied – Y90 in metal particles 50-100um – HA • Y90 Microspheres (detail) • Pre-Treatment – ECOG> 2 – Not RE candidate • Pre-Rx Diagnostic mesenteric angiogram  Vascular anatomy, Patency PV, A-P shunts • Coil embolization of non target vessels • Inferior esophageal, L inferior phrenic, Accessory left gastric, supraduodenal, retroduodenal A • Tc99m Macroaggregated Albumin scan – for assessing splancnic/Pulmonary shunt (Extrahepatic shunting)
  • 175. INDICATIONS • IHCC – RE warrants further invx • SECONDARY LIVER TUMORS • IN PRIMARY HCC • Pts within Milans criteria – Bridging to LTx • Pts outside Milans but no Malignant PVT/Mets – downstage, bring to within Milans • Advanced liver d/s – • Malignant PVT – not a CI for RE with Y90 – Have shown favorable response • Survival benefit(10-13 months) in vascular involvement • Y90 – has minimum embolic effect, so not CI in Malignant PVT • Compd to chemoemb – RE – lower TTP, lower toxicity
  • 176. • MS Trs candidates for RE • MS CRC • MS NETs(unresectable, progressive d/s – Favorable factors - BR<1.2, ECOG 0) • MS Mixed Neoplasia (Ca breast) • MS Melanoma (Y90 – favorable factors – Child A, <10 liver mets, no extrahep mets) • Post Rx F/U – • 1st Radiological F/U – 1 mth > Rx • Earlier than 6 mths – f MRI is best • RECIST & EASLD Tr necrosis criteria used • COMPLICATIONS • Post radioembolizn syndrome(Fatihue,Nx,Vx,Fever, Abd sympt) • Hepatobiliary toxicity(BR,Alb,Enz; VOD-like) • Radiation pneumonitis(CT – Batwing app) • PHTN – RE causes FIBROSIS - Usu in bilobar d/s, CASH pts) • Biliary – Biloma, Abscess cholangitis • GI complications – Inadvertnt microsph deposit Ulcer - CT Angio, PPI prophylaxis • Vascular
  • 177. CHEMOTHERAPY FOR HCC • SHARP TRIAL • Phase III study • Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol) trial • Improvement in survival of 10.7 months in sorafenib group v/s 7.9 months for placebo arm
  • 178. PREOP PVE • By – Maakuchi • INDICATIONS – • Sflr - insufficient to permit safe hepatectomy(quality of underlying liver, type of planned hepatectomy) . • Absolute contraindications for PVE: • Estd Portal HTN (>10-15 mm Hg) • Extensive Tr Thrombus
  • 179. • C/L approach for R PVE. • Occlusion balloon catheter – through L lobe into the RP branch • Embolic agent delivered in antegrade direction
  • 180. • I/L approach for RPVE extended to segment IV (Nagino et al) • Different • balloon catheters are used for B1 antegrade embolization of segment IV veins, and B2, retrograde delivery of the embolic agent into the right portal • venous system.
  • 181. • Modification of I/L approach for RPVE extended to segment IV. • C1, vascular sheath - in RP branch  5-Fr catheter – in LP system  microcatheter into seg IV branch. Particulate embolizn  Coil placement--until all the branches are occluded. • C2, After seg IV is completely occluded  reverse-curve catheter for RPVE. • C3, Access tract embolized with • coils - prevent subcapsular hemorrhage.
  • 182. PREOP PVE Trans-ileocolic Venous P.C Transhepatic C/L(Kinoshita et al) P.C Transhepatic I/L(Nagino et al) First approach introduced Laparotomy USG guided; Seg III approach; Subxiphoid route; 18 G/22G PV branches within tumor- bearing liver Ileocolic V cannulation PV catheterizn RAPV puncture - Addnal Rx needed during Sx explorn - IR suite NA, P..C approach NA DISADVANTAGE GA, Laparotomyneeded Inferior Through the FLR!!  LPV thrombus/Injury to FLR No multiple pricks, No injury to central str to be done! can be challenging - sharp angles of the RPVs – use reverse curve Catheters ADVANTAGE RPV Catheterizn – easier – no need of awkward angles better visualization of embolized portal br. on final Catheters through the FLR. I/L approach - straightfwd antegrade catheterization of
  • 183. • OPTIMAL EXTENT OF PVE – • RPVE – L lateral bisegment hypertrophy is greater after RPVE + Seg IV (50% inc) than only RPVE (31% inc) – Nagino et al • LPVE – rarely needed • SEQUENTIAL AE PVE • Rationale – • HCCs - hypervascular, supplied by arterial BF – PVE  compensatory “arterialization of liver”) in embolized segment rapid Tr progression > PVE. • Arterioportal shunts in cirrhotic livers & HCC may limit effectiveness of PVE • Sequential AE  PVE – FLR > that in PVE alone • SAE PVE – Tr necrosis > PVE alone • SAE – PVE Time gap – at least 3 wks recommended • Degree of Hypertrophy(DH)(>5%/s FLR>20%); Kinetic Growth Rate(KGR) (>2% /wk) – low postop morbidity.
  • 184. COMPLICATIONS • S.C hematoma • Hemoperitoneum, • Hemobilia • Arterio-portal shunts • A-V fistula, pseudoaneurysm • Transient liver failure • Pneumothorax • Sepsis. • Risk of injury to FLR with C/L approach – so, I/L approach should be tried first • Overall incidence of complications with either pproach – 5% • OUTCOMES – • Longterm – in HCC • No difference in PVE & Non PVE pts in OS/ DFS
  • 185. ALPPS • Hans Schlitt • Associating liver partition and portal vein • ligation for staged hepatectomy • ALPPS = R PV Ligation + In situ splitting of liver • INDICATIONS – • 1st done in Hilar cholangioCa • Bilobar CRLM • HCC in cirrhotic liver • PHC & IHC – Controversial • Indications – same as 2 stage hepatectomy, PVE/PVL • Rescue ALPPS – ALPPS wen classic 2 Stage approach/PVE – Not feasible/failed • Extrahepatic metastases, • Severe portal hypertension • High Anesthesiologic risk • Medical contraindications to major hepatectomy
  • 186. • (FLRV) before surgery, reevaluated before the 2nd stage • Measured by CT volumetry • Cut-off values fto proceed to stage 2 (> 7 - 14 days ) - sFLR > 30% (BWR > 0.5%) 40% (BWR > 0.8%) • FAILED ALPPS – • Anterior sectional PV from LPV missed during surgery deportalization of the R liver lobe – incomplete reduced hypertrophy of the FLR • Undivided PV at hilum – Absolute contraindication for ALPPS • Smadja & Blumgarts Type A & Type B – faborable for ALPPS • Type C & Type D – High risk of biliary complications > stage I ALPPS • Type E – risk of damage to L Bile duct @ stage 2 ALPPS • MHV should not be transected @ stage 1 ALPPS unles infiltrated by Tr – (To maintain the outflow to FLR)
  • 187. STEPS of R ALPPS/CLASSIC ALPPS Liver mobiliseLAD of hepatic pedicleRPV lign, transctn; liver transection hanging maneuver(anterior approach) Results – Volumetric redn of de-portalized liver(Auxillary liver), hypertrophy of FLR – Fibrin sponge/plastic bag on cut
  • 188. • Usual waiting time – 1-2 wks • Min s-FLR – 30% -40% depeding on liver qlty • Mechanism • ISS(In Situ Split) – cuts off Intrahepatic Portal collaterals to ipsilateral liver • Sx trauma to liver – cytokines  growth stimuln • But – compensatory hyper-perfusn by Hepatic A • COMPLICATIONS • MC – Biliary fistulae, collections, Sepsis • Most severe complication – Liver Failure Stage 2 – RHA RHD Divided, RHV+/- MHV - divided deportalised Liver removed
  • 189. • Technical detail to improve results • Accurate 3D volumetric calculation • Colored plastic loops during stage 1, • Intraop cholangiography • White test to detect biliary leaks at end of stage 1, • Preserving of MHV when possible • TIMING OF STAGE 2 ALPPS – • Clinincal condition good; No Sx complication • Not always @ 2 wks • Interval > 2 wks – increased difficulty stage 2 • OUTCOMES • Perioperative 90-day mortality - 9% • Severe complications, including mortality (grade > IIIa) - 28%. • Packed cell/ Stage I duration > 300 min/Age > 60 yrs/Indication of ALPPS(Primary HCC>CRLM) – significant R/F. • Leading cause of death & severe complicn post ALPPS - POLF
  • 190. Classic ALPPS – R ALPPS Central ALPPS – Division along Cantlies line btw R & L livers
  • 191. L ALPPS – Tr in L side – seg VI, VII = FLR Central ALPPS – Stage I – L lateral sectionectomy + RPVL Stge 2 – R hemihepatectomy – FLR =Seg I, IV
  • 193. • Pringle Maneuver involves clamping of A. PV Only B. PV, HA C. PV, HA, CBD and Lymphatics D. Hepatic A Only • End point of Pringle Maneuver? • Pringle Maneuver Applied, Unsuccessful – What are the probable scenarios? • Normal Liver can tolerate Inflow occlusion under normothermic conditions for? • Diseased liver can tolerate inflow occlusion under normothermic conditions for?
  • 194. PEDICLE CLAMPING • HD response to PEDICLE CLAMPING • Easiest method to reduce bleeding in Liver resectioninflow control. • Pedicular clamping – minimal HD consequence + greatest efficiency(Low filling) • Continuous clamping - ischemic injury to liver parenchyma + splanchnic congestion. • Intermittent clamping has supplanted continuous clamping – GOLD STANDARD METHOD Cardiac pre-load Mild- Mod decrease PAP 5% decrease Cardiac index 10% decrease MAP INCREASE!!!(Symp. Reflex, SVR) Recurrent clamping-declamping cycles  Hypotension Ischemia-reperfusion; toxic VD accumulation
  • 195. • WOTF is Not a side effect of continuous clamping for inflow control during liver resection? A. Post-op ileus B. Abdominal Compartment Syndrome C. Pancreatitis D. Spontaneous splenic rupture E. Hypotension F. None of these
  • 196. • HD Response to THVE • SEQUENCE OF THVE – Pedicle Infra Supra • Compensatory response to THVE – 5 min – Facilitated by bolus IV flds(PRELOADING) • MAP fall to < 80 mm – Intolerance of THVE  Declamp, optimize Cardiac preload Severe decrease PAP 25% decrease Cardiac Index 40-50% decrease MAP 10% decrease HR 50% increase SVR Severe increase
  • 197.
  • 198.
  • 199.
  • 200. • INTERMITTENT CLAMPING • MC used vasc. Clamping method • 15 min clamping. 5 min reperfusion (Unclamping) • Unclamping => No parenchymal transection • Cumulative clamping – upto 1 hr in D/S LIVER • 3 hrs – in normal liver • BEST IN DONOR HARVEST OF LIVER – No compromise in Donor safety/ Graft qlty • ISCHEMIC PRE-CONDITIONING • Initial ischemia time(10 min) F/B Reperfusion(10 min) • Protects liver against prolonged ischemia • Benefits of IPC – Only for 30 min of continuous clamping & for small vol liver resection • PHARMACOLOGICAL PRECONDITIONING • 30 min intraop preconditioning with sevofluorane – reduced postop AST & ALT • Postop complications reduced • Benefits strongest in hepatic steatosis pts
  • 201. Clamping Tech Tech. difficulty HD Tolerance Liver Tolerance Bleed Prevention Contraindicn Complicatio ns No clamping - Most Most Least - Bleed, needing BT Intermittent Pedicle clamping Least Most Intermediate Intermediate - - Continuous pedicle clamping Least Most Least Intermediate D/s liver Splancnic congestion Partial pedicle clamping Intermediate Most Most Most Pedicle involvement - Pedicle + Infrahepatic IVC clamping Least Intermedi ate Intermediate Intermediate Low CVP - HVE(Classic) Intermediate Least Least Least D/s liver/ Cardiac D/s Splancnic congestion; AKI Intermittent HVE + IVC flow preservation Most Intermedi ate Intermediate Most Juxta-caval Tr -
  • 202. • MC indication of partial hepatectomy – Metastatic lesions • Benign lesions • Malignant lesions – ideal closest Tr free margin – 1 cm; but not necessary – unavailable –ve margin in pre-op imaging – Not CI for resection • Parenchyma-sparing resections - without sacrificing oncologic efficacy • Minimal/ no risk of POLF exists if most of the specimen volume has been replaced by extensive tumor mass  compensatory hypertrophy of unaffected residual liver occurs preoperatively  limited functional parenchymal loss • Comparable resection for multiple smaller lesions or unfavorably located lesions  greater risk of POLF.
  • 203. ANTERIOR & POST SECTIONECTOMY, CENTRAL HEPATECTOMY
  • 204. ANESTHETIC CONSIDERATIONS • Bleeding in Liver resection- usu. during parenchymal transection -from HV or IVC • Deliberate retrohepatic dissection of minor& major HV before parenchymal transection – Unless the Tr location & size mandate anterior approach. • Minimal CVP < 5 mm Hg • Healthy patient – Central line not needed • 15 degree Trendelenberg position(prevent air embolism)/neutral/reverse trendelenberg • Low IVF till transection complete/Venodilator • Avoid peri-op BT – ADVERSE Periop outcome, ?increased recurrence • Indications of BT in LR - • Excessive blood loss • HD instability / Hb < 7 g/dL. • Acute Normovolemic hemodilution • Vascular isolations – Rarely used, even for Large Trs
  • 205. • STEPS OF HEPATECTOMY • Exposure • Vascular – Inflow/Outflow ctrl • Parenchymal Transection • PARENCHYMAL TRANSECTION p1584, Blumgart • Digitoclasty/Finger #/Clamp crushing – spare vessels & BD along transection plane • Hydrojet(Waterjet based device); CUSA – Parenchmal destruction & vessel, BD preservation • V/S Digito/finger/clamp – greater accuracy, +/- increased speed - poor hemostasis • RFA based – Tissuelink, AquaMantys, Habib4X – Hemostatic devices – Rapid indiscriminate coagln cut surface- • Bipolar(LIGASURE), US vessel seal(Harmonic scalpel) – seal BV 7-8 mm dia. • Stapling devices – Ctrl large vessels in plane OR as primary method of transection
  • 206. ANTERIOR APPROACH, HANGING MANEUVRE(Lai et al) • INDICATIONS – FOR RIGHT HEPATECTOMY • Larger Trs invading diaphragm • Invading lateral wall of IVC higher • Large HCCs/Adenomas – which may # or bleed during mobilization • May avoid risks of massive bleeding from HV avulsion, prolonged ischemia in remnant liver, spillage of cancer cells • HANGING MANEUVRE • To ctrl bleed in deeper parenchymal planes • Pre-requisite – Absence of Tr in contact with anterior IVC wall
  • 207. • Exposure of liver at level of suprahepatic IVC • Dissect btw MHV & RHV for 2 cm • Expose liver @ level of infrahepatic IVC • Caudate lobe tributaries to IVC –ligated, divided • Dissection of plane anterior to IVC – Kelly clamp – upwards btw IVC, Caudate comes out btw RHV & MHV • Umbilical tape passed thru this tract lift liver away from IVC • RPV, RHA divided • Parenchymal transectn(with pull on umbiical tape) exposed deeper planes easily • IVC protected by umbilical tape traction • IVC exposed  dissection of R side IVC wall to separate it from Tr • Division of Hepatocaval lig, RHV, RIHV - now
  • 208. PARENCHYMA SPARING LIVER RESECTION TECH. Mini-Meso hepatectomy – Seg VIII, Part of seg I – Tr invading MHV 4 cm from MHV-IVC confluence R Posterior sectionectomy – for posteriorly located Trs
  • 209. • Upper Transversal Hepatectomy – for Trs invading RHV – IVC confluence • Redefining ANATOMICAL RESECTION – Removal of territory of one or more 3rd order portal br. • Assisted by – IOUS, NIR fluorescent imaging, Biliary/ Vascular injection of ICG • RH v/s RPS – POLF – more likely in RH; severe liver insufficiency – RH> RPS; No diff in OS/ Other short term parameters
  • 210. CRLM • PRE-OP EVALUATION • Med. Resectability(PS, Comorb, liver status) • Oncologic. Resectability(Tr markers, Rdio- resectability, Scopy) • Technical resectability (Volumetric) • CECT Abd, Chest, Pelvis • MRI - Indeterminate lesions; Liver-sp. Contrast sub cm lesions in S.C location; in Macrovesicular steatosis • PET-CT – prior to Metastasectomy, suspected recurrence, RT planning, response assessment, Incidental CRLM discovery (occult omental/ peritoneal d/s) • Evaluate indeterminate nodal/ST mass on CT/ MRI; • unremarkable scans but elevated CEA level out of proportion to liver d/s.

Editor's Notes

  1. Wall thickening/irregularity/papillary mural projections/ nodules/internal septations/ intracystic debris - neoplastic etiology