Cadaveric Liver Transplantation - Where do ‘we’ stand Today

Dr. Rajasekhar PerumallaMS, FRCS

Senior Consultant Transplant SurgeonSIMS (SRM Institute of Medical Sciences)

VadapalaniChennai

Important milestones in transplantation

Dr.Thomas Starzl

1963- Denver, Colarado,US• INTRODUCTION OF CYCLOSPORINE

A – JEAN BOREL• SIR ROY CALNE – CAMBRIDGE

UNIVERSITYInitial results 130 LTX by 1970, 12 alive in 1976Scope for improvement

Transplant scenario in India

Brain Death and deceased donor organ donation is legal - Human Organ transplantation Act 1994

Liver transplant - First DDLT - 1998First LDLT - 1999 (Paediatric)First LDLT - 2000 (Adult)

Transplants Oct 2008 to Jan 2015

Donors From TN 587 Heart 116 Lung 50 Liver 542 Kidney 1052 Pancreas 4 Small Bowel 1 Total Major organs 1765 Heart Valve566 Cornea 886 Skin 13

Total Organs 3231

Liver transplant - survival

1 year survival - 88- 90% 2 year survival - 80- 85% 5 Year survival - 70- 75%

Complication rate – 10- 15%Artery, Bile duct, Infection, rejection

Improved outcomes

Patient selection Organ preservation Refined surgery & anaesthesia Immunosuppression Early recognition of complications &

management

Prognostic Models

CTP Score MELD score

Importance of HCC screening in Cirrhotics

6 monthly AFP and Ultrasound

Deceased Donor Vs Living Donor – Which to offer and when?

Time available for the Recipient -Stable – Can waitStable – not ideal to waitUnstable

Donor

Deceased donor 1. Brain Dead Donor2. DCD (Donation after cardiac

death) Organ preservation time

Liver – 12 -24 hrs Whole organ / Reduced graft / Split

Organ harvesting /Procurement

Laparotomy/Asessment Aortic cannulation Portal cannulation Goal: Cool the organs and perfuse

with preservative solution (HTK (Custodial)

UW (Belzer) while exsanguinating the organs

Cold Ischemia Time

Retrieval of liver following clamping the Aorta

Packaging and Transport Recipient Hepatectomy Implantation of New Liver –

Vena Caval anastomosis, Portal Vein Anastomosis, Reperfusion

TOTAL TIME 6 – 12 hrs.Always a race against Time!

Selection Selection of transplant type depends on Organ availability ABO match Physical size (HT, WT, Abdominal girth) Medical condition - MELD, CTP score) Age match – Donor / Recipient DDLT preferred in a recipient

High BMI Portal vein thrombosis Re-transplantation Sick recipients

In India: organ shortage

DDLT- Is there a need for Speed?

Keys to a safe and quick transplant Prepare well - Know your patient, review the

case history, diagnosis & Lab values. Review the CT scan & Know the anatomy Start slowly, progress gradually with careful

mobilisation of liver & no traction Ensure haemostasis at every step

DDLT is usually faster Implantation is less complex & quicker

DDLT Emergency - Race against time to CIT

Recipient hepatectomy

Level of dissection

High ligation of the hilar structures: Arteries and bile ducts

Beware of vascular intimal dissection

LDLT- High ligation of structures

Cava preserving hepatectomy

Preferred technique

Avoids caval clamping

Could be avoided in select DDLT cases.

Veno venous bypass

Difficult hepatectomy

Caudate lobe hypertrophySevere portal hypertensionVolume overload- Tissue oedemaRetransplantationPrevious upper abdominal surgeryAbdominal cocoon

Temporary porto caval shunt Belghiti et al

Difficult recipient hepatectomyTraining periodNo portal hypertension

Acute liver failure Non cirrhotic

Implantation - Classic technique

Hepatic vein implantation

DDLT

Piggyback technique Preferred Single cava

anastamosis Cavacavoplasty

Side to side cavo-caval Caval replacement

Budd chiari syndrome Massive caudate lobe Retransplantation

LDLT

Multiple veins to be drained

RHV in right lobe grafts

Seg 5/8/ IRHV reconstruction

Caval anastomosis – “pyggy-back” technique

Caval anastomosis – Belghiti technique

Final aspect of anastomoses

1. Hepatectomy – can sometimes be the toughest2. Anhepatic Phase – Major role for Anesthesiologist3. Reperfusion – “ Anesthesia- watch for Toxin release

to the heart , Surgeons - Watch for golden bile”

Good graft function

Haemodynamic stability Awakening from anesthesia Clearence of lactate Resolution of hypoglycemia Normalisation of coagulation profile Resolution of elevated transaminases Bile (Golden) production on the table

Uncomplicated post op period

Stable Haemodynamics- Minimum to no inotropes

Patient wakes up - 1- 2 hrs. Acid base balance Extubation – 4-6 hrs. Doppler – day 1 Out of ICU to wards Diet – NE feeds 6 hrs. to 12 hrs. OUT OF HOSPITAL – 10 -14 days

Factors? : Immediate outcome

Graft selection / Graft quality Organ preservation Warm & cold ischaemia times Donor – Recipient matching Surgical & Medical problems

Post Op Care –MULTI-FACETED APPROACH

FLUID AND ELECTROLYTE BALANCE

RESPIRATORY STATUS RENAL FUNCTION – RRT INFECTION CONTROL IMMUNO-SUPPRESSION IMAGING ALL THE

‘PLUMBING’

Early complications

Primary Non Function of Graft (2%) Delayed Graft Function Technical (Arterial, bile duct) 10-

12% Acute Rejection Infection

Post Transplant Phase - PNF

Age Electrolyte imbalance Inotropes Prolonged ICU stay CIT PNF Prevention

Careful management of donor

Long Term Complications

Recurrence of primary disease Metabolic complications –

Hypertension Renal failure Dyslipidemia PTDM (Immunosuppression related)

Malignancy- PTLD, Skin tumors

Care of Transplant Patient

Primary Care physician

Hepatologist

Transplant Team

Expansion of the Organ Donor Pool

Improving results Increasing demand Scanty resource Decrease the waiting list

mortality Efforts are on to expand the pool

Future?

ORGAN SUPPLY – “Political”

Opting out system (Spanish model)

Infrastructure? ITU beds

ORGAN SUPPLY – Surgical

Using marginal grafts

Resuscitation of grafts Ischaemic preconditioning

Avoidance of cold ischaemia

Fewer technical complications

Split liver for 2 adults

Future?

The First Split & Auxiliary Liver Transplant in India was performed by Prof Mohamed Rela and his team to save the lives of two different individuals.

Ms. Himani Koshala and Ms. Kamala Bulledulla

1919thth September 2009 September 2009

Split the liver graft for 2 adult recipients

Ex-situ Split Liver TransplantationKing’s College Hospital – Survival data

n 1 yr 3 yr 5 yr

Overall patient survival 256 87% 84% 84%

Patient survival – LLS 140 90% 88% 88%

Patient survival – RL 116 85% 81% 80%

Results of Ex-situSplit Liver Transplantation

Author Year Number Age group Technique Patient Graft

Survival % Survival %

Broelsch et al 1990 30 Adults Ex situ 67 55

Otte et al 1995 29 Mixed Ex situ 79 69De Ville et al 1995 96 Mixed Ex situ 71 64

Azoulay et al 1995 27 Mixed Ex situ 79 79

Rela et al 1998 41 Mixed Ex situ 90 88Mirza et al 1998 24 Mixed Ex situ 78 68

Reyes et al 2000 12 Paediatric Ex situ 64 4513 Adult Ex situ 83 -

Azoulay et al 2001 34 Adult Ex situ 88 (LLS) 74 (RL)

Kings 2001 156 Mixed Ex Situ 88.6 88

Biliary anatomy of Caudate Lobe

Marginal Donor

Definition Organs considered unsuitable for

transplantation are currently being used.

New Terminology “Marginal” donor, “Expanded” donor “Extended criteria” donor

Marginal Donor Older donors Diabetes mellitus Hypertension Renal insufficiency Selected cases

Hepatitis B & C HIV

Marginal Donor-Disadvantages

risk of delayed graft function Primary non function (PNF)

Assessment Extended Criteria Donor

Donor age and history Donor haemodynamics Donor Anatomy Donor liver Biopsy Pump parameters Recipient selection

important

Steatotic graft Western population: steatosis is prevalent in

30 to 70% of people Most common type of ‘‘extended criteria’’

organs Problems – depending on severity of steatosis

Primary/delayed function Post transplant complications Poor long-term outcomes ??

Nocito A, et al. J Hepatol 2006;45:494–499

Steatotic Graft - Assessment

Assessment Visual inspection and palpation Biopsy – Two cores from the right and left liver were

regarded to best predict overall liver histological characteristics

Frozen section may overestimate

Hepatic Steatosis Quantitative evaluation - based on the

percentage of hepatocytes containing cytoplasmic fat inclusions Mild - ≥ 30% Moderate - 30 -60%, Severe - > 60%

Fatty infiltration - Two categories Macrosteatosis Microsteatosis

1.

Donor Risk Index

May be acceptable to transplant with up to 60% steatosis in the graft

McCormack L, et al. Journal of Hepatology 2011; 54: 1055–1062

Cold ischemic time 5hrs. for grafts with steatosis

Consider donor < 40 year Recipient MELD:

Those with low MELD seem to tolerate steatotic grafts betterBest scenario would be use this for low MELD score recipients with urgency such as those with HCC

Long term outcome

Steatotic Graft show a dramatic decrease in fatty infiltration after LT

Mechanism – not fully understood Factors that negatively affect this reversal of steatosis - donor age

(>50 years) and prolonged cold ischemia time (>12 h) Severe macrosteatosis : Biliary complications Steatosis in the liver graft – negative prognostic factor

for HCV recurrence Literature is divided on the effect of donor graft steatosis as a

facilitator or stimulator of fibrosis on patients with post-LT HCV recurrence

Baccarani U, et al. Clin Transplant 2009.

Li J, et al. Transplant Proc 2009;41: 3560–3563.

Future Challenges Ongoing work by the Pioneers

Long Term Complications IMMUNE Tolerance

Ever Increasing Demand Xenotransplantation

LIVER TX– TEAM EFFORT

TX SURGEONS ANESTHESIOLOGISTHEPATOLOGISTINTENSIVISTSCRUB NURSEPERFUSIONISTDIALYSIS TECHNICIANSBLOOD BANKPATHOLOGISTLAB PERSONNELTX COORDINATORS

Don’t take your Organs to heaven, heaven knows we need

them here.

Thank you