Liver: An EnigmaLiver: An Enigma
ByByDr. S K Mathur MS, FACSDr. S K Mathur MS, FACSSr. Consultant GI SurgeonSr. Consultant GI Surgeon
HPB Surgery & Liver Transplantation, HPB Surgery & Liver Transplantation, Wockhardt hospitals, Mumbai
Past President : Indian Chapter of International HPB Association Indian Association
LiverLiver
Unique Unique
Functionally ComplexFunctionally Complex
EnigmaticEnigmatic
ResectableResectable
TransplantableTransplantable
Liver: An EnigmaLiver: 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 VolumetryNormal Liver :
Segments Volume
5 + 8 30 %
6 + 7 35 %
1 + 4 20 %
2 + 3 15 %
65 % of Right Liver65 % of Right Liver
35 % of Left Liver35 % of Left Liver
(Stone et al Am J Surg 1969)(Stone et al Am J Surg 1969)
Liver : UniquenessIt has large functional reserve
For survival:For survival: 35% of functional liver 35% of functional liver
Liver : UniquenessCapacity 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 enigmato Clinicians
Liver Tumors
Parenchymal Liver Diseases
Cirrhosis
Liver cell failure Death
Liver Tumors• Benign
- FNH
- Adenoma
- Hemangioma
• Cystic
- Congenital
- Hydatid
- Cyst adenoma
• Infective: - Tuberculoma
MalignantPrimary: - HCC - hepatoblastoma - cystadenocarcinoma - Neuroendocrine - Lymphoma
Metastasis: - Colo-rectal - Neuroendocrine
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
Chronic Viral Hepatitis:
• 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
Etiology Etiology ::
Hepatocellular Carcinoma
Cirrhosis of liver: due to-• Chronic Alcohol abuse• Non-alcoholic Fatty Liver Disease (NASH)• Other Causes: - Budd - Chiari syndrome - 1 antitrypsin deficiency - Haemochromatosis• Aflotoxins : Toxins of Aspergillus flavus & parasiticus (B1,B2 & G1,G2) Food products: e.g. peanuts & grains
Etiology Etiology ::
• Synthetic heaptocarcinogens :
- Azo dyes, aromatic amines,
- pesticides, chlorinated hydrocarbons• Miscellaneous :
- Oral contraceptives
- Anabolic steroids
- Radiation
- Thorotrast
Hepatocellular Carcinoma
Etiology Etiology ::
Hepatocellular CarcinomaClinical 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
• 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
• MRI - Dynamic bolus gadolinium injection
(diagnostic accuracy > CT)
• Hepatic Angiography
• PET Scan
For small HCC (3mm)For small HCC (3mm)
Imaging Modalities:
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
Local Ablation Therapies:
• Intra-tumoural ethanol injection
• Radio frequency ablation
• Cryoablation
Non surgical therapiesNon surgical therapies
Surgical TherapiesSurgical Therapies
Liver ResectionLiver Resection
Liver TransplantationLiver 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-Deemed not suitable for re surgery i.e. re-resection of the liver tumor: resection of the liver tumor:
•Resurgery on liver is considered hazardous due Resurgery on liver is considered hazardous due to adhesions to surrounding organs:to adhesions to surrounding organs: e.g. Diaphragm, colon, duodenume.g. Diaphragm, colon, duodenum
•One tumor nodule was close to & extending One tumor nodule was close to & extending behind the IVCbehind the IVC
IVC
Tumors Tumor
Liver
Advised Palliative Treatment:Advised Palliative Treatment: Underwent two cycles of TACE in April Underwent two cycles of TACE in April and June 2009and June 2009
One tumor nodule which was flush with One tumor nodule which was flush with the IVC could not be embolisedthe 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 ScanCT Scan
Sectorectomy
Right hepatectomy
Story of a patient with Story of a patient with recurrent liver cancerrecurrent liver cancer
Video
•Postoperative course was uneventfulPostoperative course was uneventful
•Out of ICU on Day 2Out of ICU on Day 2
•Discharged from the hospital on Day 6Discharged from the hospital on Day 6
•Histopathology reported as necrotic tumor at the Histopathology reported as necrotic tumor at the previous resection siteprevious resection site
•Viable tumor adjacent to the stump of the RHV and Viable tumor adjacent to the stump of the RHV and IVCIVC
Dealing with Cancer and Terrorism
Prevention
Early detection
and effective damage control
Hepatocellular Carcinoma
• Prevention
– HBV infection: Vaccination programme– HCV: Safe Blood bank Practices– Alcoholism : Awareness & Control– Obesity Control: Life style Modification– Aflotoxins : awareness
ConclusionsConclusions
• Screening X
• Surveillance Yes
Diagnosed cases of Cirrhosis
• Programme:
- AFP every 3 month
- USG every 3-6 months
• Any suspicious new lesion : CECT
Early DetectionScreening or Survilliance
• 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
Appropriate Management