Liver: An Enigma

By
Dr. S K Mathur MS, FACS
Sr. Consultant GI Surgeon
HPB Surgery & Liver Transplantation,
Wockhardt hospitals, Mumbai

Past President :
Indian Chapter of International HPB Association
Indian Association
 Liver
Unique

Functionally Complex

Enigmatic

Resectable

Transplantable
 Liver: An Enigma

•Liver is the largest organ in the body: wt 1.2-1.5 Kg

•Liver is the most complex organ in the body

•From ancient times liver is considered the “organ of fate”

•Egyptians considered the liver to be the “seat of the life force”

 Liver: a Unique organ

• Anatomy:
- Dual blood supply
* Portal Vein
* Hepatic artery
HA supplies 35% of blood flow

 Segmental anatomy
 Prediction of Hepatic
Insufficiency
Hepatic Volumetry
Normal Liver :

Segments Volume
5+8 30 %
65 % of Right Liver
6+7 35 %

1+4 20 %
35 % of Left Liver
2+3 15 %
(Stone et al Am J Surg 1969)
 Liver : Uniqueness
It has large functional reserve

For survival:
35% of functional liver
 Liver : Uniqueness
Capacity for Regeneration

In 6 weeks liver regenerates

to 90% of its original volume
 In Greek mythology, Prometheus (Ancient
Greek:"forethought")[1] is a Titan known for his
wily intelligence, who stole fire from Zeus and gave it
to mortals for their use.[2] Zeus then punished him
for his crime by having him bound to a rock while an
eagle ate his liver every day only to have it grow back
to be eaten again the next day.
 Liver: an enigma
to Clinicians

 Liver Tumors

 Parenchymal Liver Diseases

Cirrhosis

Liver cell failure Death

 Liver Tumors
• Benign
Malignant
Primary:
- FNH - HCC
- Adenoma - hepatoblastoma
- Hemangioma - cystadenocarcinoma

• Cystic - Neuroendocrine
- Congenital - Lymphoma
- Hydatid
Metastasis:
- Cyst adenoma - Colo-rectal
• Infective: - Neuroendocrine
- Tuberculoma
 Liver Cancer
(Hepatocellular Carcinoma)
 Hepatocellular Carcinoma
• 80 % of all liver tumors
• Male : Female = 3 : 1

• HCC Underlying chronic liver

disease (Cirrhosis : 80-90%)
Normal Liver

Tumour doubling time :

median 4-5 months (<5cm)
 Hepatocellular Carcinoma
• Prevalence:
* Annual incidence of 1 Million new cases
* Geographical distribution parallels
The incidence of HBV infection
• High Incidence areas:
South-east Asia: 10-20 per 100,000 population
• Intermediate Incidence:
Japan, Middle-east, Mediterranean
• Low Incidence: India, South Africa
• Lowest Incidence: 1-3 per 100,000 population
Australia, USA, Europe
 Hepatocellular Carcinoma
• Prevalence:
* Annual incidence of 1 Million new cases
 Digestive cancers at TMH
1994-95
Site 1994 1995

All GI 2277 2347

Esophagus 902 921
Large bowel 617 666
Stomach 359 341
Gall bladder 161 167
Pancreas 1 12 134
Liver 88 88
Others 28 30
 Hepatocellular Carcinoma
Etiology
: Viral Hepatitis:
Chronic

• Hepatitis B virus: 80 % of all HCC have HBs Ag +ve

Relative risk : 200 fold greater than non-infected

- Duration of Chronic HBs Ag carriers and risk of HCC:

Strong correlation
Childhood infection : risk of HCC 40%
Adults: risk of HCC 10%

• Hepatitis C virus: - In Japan, Spain, and Italy

80% of all HCC are +ve for Anti HCV
 Hepatocellular Carcinoma
Etiology
:
Cirrhosis of liver: due to-
• Chronic Alcohol abuse
• Non-alcoholic Fatty Liver Disease (NASH)
• Other Causes:
- Budd - Chiari syndrome
- α 1 antitrypsin deficiency
- Haemochromatosis
• Aflotoxins :
Toxins of Aspergillus flavus & parasiticus
(B1,B2 & G1,G2)
Food products: e.g. peanuts & grains
Hepatocellular Carcinoma
Etiology
:
• Synthetic heaptocarcinogens :
- Azo dyes, aromatic amines,
- pesticides, chlorinated hydrocarbons
• Miscellaneous :
- Oral contraceptives
- Anabolic steroids
- Radiation
- Thorotrast
 Hepatocellular Carcinoma
Clinical Presentations
• Delayed: - Absence of Specific Symptoms
- Non-palpable liver
- Large Functional hepatic reserve
• Anorexia & Weight loss
• Fever
• Pain in abdomen: Rupture & bleed:
Localised: D/D Acute MI
• G.I. bleed: - Variceal due to acute PV Thrombosis
- Hemobilia
• Obstructive Jaundice
 Hepatocellular Carcinoma

Diagnosis :
Tumour Markers: -
- AFP > 400 ng/ml

- DCP (des - y - carboxy prothrombin)

- CEA
 Imaging Modalities:

• USG
• CT : Contrast enhanced CT - 70 %
Biphasic Helical CT (PV : tumour v/s bland thrombus)
a) Arterial phase - Hyperdense
b) Portal venous phase - Hypo or isodense
c) Delayed peripheral enhancement – capsulation

• CT angiography
• Lipiodol CT For small HCC (3mm)

• MRI - Dynamic bolus gadolinium injection

(diagnostic accuracy > CT)
• Hepatic Angiography
• PET Scan
Hepatocellular Carcinoma

Treatment Options:

 Surgical

Non-Surgical
 Hepatocellular Carcinoma

Non surgical therapies

• Systemic chemotherapy

• Intra-arterial chemotherapy (TAC)

• Trans arterial embolisation (TAE)

• Trans Arterial chemo-embolisation (TACE)

• Trans arterial Radio-embolisation: I131or Y90

 Non surgical therapies
Local Ablation Therapies:

• Intra-tumoural ethanol injection

• Radio frequency ablation

• Cryoablation
Surgical Therapies

Liver Resection

Liver Transplantation
 SURGERY- ANTERIOR
TRANSHEPATIC RESECTION

Weight 2 .5Kg
 Management of HCC
• Surgical resection : best therapy
Survival - 3yrs : 68 – 76%
- 5yrs : 51 – 68%
*Resection rates : 9 – 37%
(Ref: SCNA 2004, Ann Surg 2002)
• Liver Transplantation :
Cures underlying liver disease
Survival : 5yrs : 50 – 60% (71 – 78%)
Selection criteria : T1 & T2 lesions
Problem : Donor shortage
( Ref: Am J Surg 2002, Arch Surg 2001, Hepatology 2001)
 Management of HCC

• Recurrence of Liver tumor after resection:

Incidence: 30%
What are the treatment options?

Repeat Surgery
( Re-resection of Liver)
Or
Non- surgical therapies
Story of a patient with recurrent
liver cancer

Agony to Smile
 HISTORY

• 58 year old male

• October 2006: Diagnosed to have a tumor in his liver on
USG
• CT Scan Confirmed the tumor to be single and localised
in his right half of the liver
• CT guided biopsy reported as:
well differentiated Hepatocellular Carcinoma
• Tumor Marker : AFP was normal
 Story of a patient with
recurrent liver cancer

October 2006:
• Evaluated at a Cancer hospital
• No Co –morbid diseases
• No spread of tumor out side liver
• He underwent Liver resection for his tumor
• Was asymptomatic 2 ½ years post surgery.
• In April 2009 : during a follow up USG at the
previous hospital
- detected to have recurrence of his tumor at the
cut margin of the liver
- CT Scan confirmed the recurrence of the
tumor : Three tumors close to each other
•Deemed not suitable for re surgery i.e. re-
resection of the liver tumor:

•Resurgery on liver is considered hazardous due

to adhesions to surrounding organs:
e.g. Diaphragm, colon, duodenum

•One tumor nodule was close to & extending

behind the IVC
Liver

Tumors Tumor
IVC
Advised Palliative Treatment:

Underwent two cycles of TACE in April

and June 2009

One tumor nodule which was flush with

the IVC could not be embolised
 Management of HCC
• Recurrence of Liver tumor after resection:
Incidence: 30%
What are the treatment options?

Repeat Surgery
( Re-resection of Liver)
Or
Non- surgical therapies
 Selection Criteria for Repeat Hepatectomy in Patients With
Recurrent Hepatocellular Carcinoma Masami Minagawa, MD,*
Masatoshi Makuuchi, MD,* Tadatoshi Takayama, MD,† and
Norihiro Kokudo, MD* Ann Surg. 2003

• The most widely used treatment of intrahepatic recurrence is

transarterial chemoembolization (TACE).
• The 5-year survival rate has ranged from 0% to 27% in
patients with postresectional recurrence, even with repeated
TACE.
• It is questionable whether this procedure actually enhances
survival in such cases.
 Selection Criteria for Repeat Hepatectomy in Patients
With Recurrent Hepatocellular Carcinoma Masami
Minagawa, MD,* Masatoshi Makuuchi, MD,* Tadatoshi Takayama, MD,† and
Norihiro Kokudo, MD* Ann Surg. 2003

• Repeat resection for recurrent HCC has been

reported to be a highly effective treatment in selected
patients.

• The 5-year survival rate after repeat resection has

been reported to be from 37% to 70%.
Repeat resection for recurrent HCC in selected
patients:-
hepatic resection is the treatment of choice for patients

• who have previously undergone resection of a single

HCC at the primary resection
• in whom recurrence developed after a disease-free
interval of 1 year or more
• the recurrent tumor had no portal invasion.
 Story of a patient with
recurrent liver cancer
• August 2009:Came for 2nd opinion:
Evaluation at Wockhardt Hospitals:
 Patient is well built and nourished
 No comorbid illness
 No spread of tumor out side the liver
 Remaining liver normal
 Treatment Offered: Re-resection of the liver
CT Scan
Sectorectomy
Right hepatectomy
Story of a patient with
recurrent liver cancer

Video
•Postoperative course was uneventful

•Out of ICU on Day 2

•Discharged from the hospital on Day 6

•Histopathology reported as necrotic tumor at the

previous resection site

•Viable tumor adjacent to the stump of the RHV and

IVC
 Dealing with Cancer and Terrorism
 Prevention

 Early detection

 and effective damage control

Hepatocellular Carcinoma
Conclusions
• Prevention

– HBV infection: Vaccination programme

– HCV: Safe Blood bank Practices
– Alcoholism : Awareness & Control
– Obesity Control: Life style Modification
– Aflotoxins : awareness
 Early Detection
Screening or Survilliance
• Screening X
• Surveillance Yes
Diagnosed cases of Cirrhosis
• Programme:
- AFP every 3 month
- USG every 3-6 months
• Any suspicious new lesion : CECT
 Appropriate Management
• Resection is the best treatment
Assessment for resection by a Liver Surgeon
• Unresectable: due to Anatomical factors
- Chemo-embolisation +/- RFA: to shrink
- Portal vein Embolisation:
Induce hypertrophy of Normal liver
Re-asses for Resection
• Unresectable due to Advanced liver disease:
Evaluate for Liver Transplantation
 Appropriate Management
Unresectable & Non-Transplant Candidates
- No evidence of Metastasis
• Consider Palliation:
- PEI
- RF Ablation
- TACE
- Trans arterial radio-embolisation

• Long-acting Octeriotide: Selected patients