Www.medicalppt.blogspot.com Dr. Mukesh PUBLISHED BY MAHARANI LAXMI BAI MEDICAL COLLEGE, JHANSI “MANAGEMENT OF LIVER SECONDARIES”

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Dr. MukeshPUBLISHED BY


MAHARANI LAXMI BAI MEDICAL COLLEGE, JHANSI

“MANAGEMENT OF LIVER SECONDARIES”


MANAGEMENT OF LIVER SECONDARIES

METASTASIS

The term metastasis connotes the development of secondary implants discontinuous with the primary tumor, possibly in remote tissue.

A liver studded with metastatic cancer


INCIDENCE

Metastasis is the most common neoplasm in an adult liver.

Liver is the second most common site for metastatic spread,

after the lymph nodes.

The primary sites most commonly metastasizing to the liver

are - Colon (65%)

Pancreas (63%),

Breast (60.6%),

Gallbladder and extrahepatic bile ducts (60.5%),

Ovary (52%)

Rectum (47%)

Stomach (45%)

Lung (36%),

Kidney (26%)


Nearly two-third of patients with colorectal cancer will develop

hepatic metastasis.

25% to 50% of patients dying of cancer are found to have

hepatic metastasis.

TERMINOLOGY

Metachronous - Metastases appearing much latter than

treatment of primary eg. melanoma of chord.

Synchronous - Primary & metastasis detected at the same time.

eg-carcinoma stomach.

Precocious - Metastases appearing before primary is suspected.

eg-carcinoid, rectal carcinoma.


PATHOPHYSIOLOGY

Metastasis reach to liver by four routes -

1. Direct invasion (stomach, colon, bile ducts, gall

bladder)

2. Lymphatics (breast and lungs via mediastinal

nodes)

3. Hepatic artery (lung, melanoma.)

4. Portal vein (colorectal)


PRESENTATION

Incidental

Dull aching pain in right hypochondrium,

Loss of appetite, asthenia, weakness, mailase,

Jaundice, anemia, vomiting,

Hepatomegaly, ascitesEnlargement of Both lobes, sharp lower border,

nodular surface, hard consistency,


Prognostic factors -

1. No. of metastasis

2. Resection margin status

3. High preoperative CEA

4. Size of largest tumor

5. Stage of primary tumor

6. Disease free interval

7. Synchronous disease

8. Extra hepatic disease

9. Peripheral nodal status


Preoperative Patient Evaluation

Before even thinking on performing a liver resection, it is

necessary a thorough oncologic examination, seeking other

localizations, and also to verify the absence of contra-

indications.

Regarding morphological tests, an abdominal US, CT and

afterwards a MRI, allow to acquire a better knowledge

regarding number of metastases, precise location,

relationship with the portal pedicle and the hepatic veins.


Pulmonary localizations must be ruled out

systematically, using CT examination. If these

lesions are resectable, they don’t constitute a

contraindication to liver resection.

A colonoscopy is always performed to rule out

recurrence, even if the primary tumor has already

been resected.

If necessary, a bone scan or a brain CT can be

performed.

Regarding the blood chemistry, it consists of liver

function tests, tumor markers, coagulation profile.


Evaluation of functional hepatic reserve - in patients who

received neoadjuvant chemotherapy or those with a preexistent

liver pathology (hepatitis, cirrhosis. Tests used are--

Child pugh class

Indocyanine green clearance test

Aminopyrine & phenylalanine breath test

Galactose elimination rate

Hippurate ratio

SPECT


Treatment Options

A. Surgical resection

B. Ablation

1.Cryotherapy

2.Radiofrequency ablation

3.Laser interstitial thermal therapy (LITT)

4.Microwave coagulation therapy

C. Chemotherapy

1.Neoadjuvant

2. Intra-arterial

3.Systemic

4.Chemoembolisation


D. Radiotherapy

1. Stereo tactic body radiation

2. Selective interstitial radiation therapy

E. Liver transplantation

AIMS OF TREATMENT

Curative intent - Multimodal treatment may allow complete

tumor clearance

Combination of surgery + other ablative techniques

Neoadjuvant treatment to improve resectability


Palliative intent

Decision tree for patients with hepatic metastases. Beginning with treatment of the primary tumor, optimal management depends on careful weighing of multiple factors

and making the best individual treatment choice.


Surgical resection

80%-90% of resections of hepatic metastasis are for

colorectal cancers.

First hepatic resection for hepatic metastasis-by Garre in

1988.

1949 total right lobotomy by Wangensteen.

1959-hepatic artery infusion.

1972 implantable pump.


Functional anatomy

It is composed of eight segments each of which is supplied by a

single portal triad composed of a portal vein hepatic artery &

bile duct.

Segmental anatomy of the liver as seen at laparotomy in the anatomic position (Surgical and radiologic anatomy of the liver and

biliary tract)


Anatomical Resections

They follow the liver segmentation principles described by

Couinaud. They are considered as minor, when less than 3

segments are resected, or major, when resection includes more

than 3 segments.

Nomenclature for Most Common Major Anatomic Hepatic Resections



The most common approach to a anatomic resection in most common order,

Mobilization of liver

Dissection of inflow and outflow structure

Division of inflow

Division of outflow

Parenchymal transection

Non-Anatomical Resections

They include the resection of a portion of the liver independently of the liver scissors and glissonian pedicles. They refer mainly to metastasectomies. The liver resection depends on the size of the tumor.


Rules to Respect During Hepatectomy

Independently of the type of liver resection, one must follow

these rules in order to avoid postoperative complications:

1. Functional liver parenchyma preservation of at least 30% of

the total liver mass, to avoid hepatic insufficiency.

2. Limit blood loss, in order to avoid transfusions, because it is

a known risk factor that favors recurrence.

3. Resect the 1 mm margin, to reduce the risk of recurrence.

4. Resect glissonian pedicles destined to the remaining

segments, to avoid segmental exclusion, ischemia and

necrosis, and biliary fistulas.


ABLATION

1. Cryotherapy Destruction of tumor cells by freez thraw.

Probe positioned over tumor

Liquid nitrogen is circulated through tip of probe

Temp lowered to -100° C

1-3 cycles of freezing for 15 mins with spontaneous periods of thraw

Lethal temp -20° C

Intracellular or extra cellular ice forms

Ice ball of ~3-6cm

Complications - biliary, abscess, myoglobinuria, haemorrhage, coagulopathy, cryoshok


2. Radiofrequency ablation

Radiofrequency waves (high frequency alternating

current - 460khz) are converted into thermal energy

Friction from rapidly moving ions results in heat

Temp of ~60°C

Coagulative necrosis

Open/laparoscopic or percutaneous technique

Effective with tumors upto 5 cm

Complications - bilioma’s, biliary fistula’s, stricture’s

abscess


3. Laser interstitial thermal therapy (LITT)

Placement of laser fiber or fibers directly into the

tissue to be treated.

Infrared laser producing lethal thermal injury to tumor

cells

LITT utilizes diod laser or more frequently Nd-YAG

laser

Coagulative necrosis

Procedure is usually performed under MRI.

Extensive use if MRI is its major drawback.


4. Microwave coagulation therapy

Uses microwave of frequency 2450 Mhz

Produces heat by stimulation of water molecule

Produces rapid frictional heating and coagulative

necrosis

5. Intratumoral alcohol injection

Causes denaturation of protein leading to cell death..

Can be used for tumors <3cm.


RADIOTHERAPY

1. Stereo tactic body radiation

Tolerance of liver to radiation is poor.

Conformational radiation therapy using multiple field &

beam angles is used to deliver large doses to a target

sparing surrounding normal tissues.

2. Selective interstitial radiation therapy

Micro spheres containing yttrium 90 (sir spheres)

Injected via hepatic artery


Tumor cells receive a higher proportion of there blood

supply via hepatic artery.

200-300 Gy to tumor ,15-50 Gy to liver

B radiation with a penetrance of 2-3 mm

Half life of 64 hours.

Percutaneous cannulation of hepatic artery

Administration of spheres

Spheres selectively lodge into tumor cells


CHEMOTHERAPY

1. Neoadjuvant

Patients at high risk of recurrence should receive

neoadjuvant chemotherapy.

Drugs include oxaliplatin, irinotecan, 5fu, leucovorin.

20-30 % of patients who were unrespectable will be

rendered potentially respectable.


2. Hepatic artery infusion therapy (implantable

pump)

Rationale is that hepatic metasis is perfused almost

exclusively by hepatic artery.

Injection of floxuridine into hepatic artery demonstrates

mean tumor fudr levels are significantly increased

Can be administered by implantable pumps

Most common problems with hai are hepatic toxicity &

ulceration of stomach & duodenum.

Addition of dexamethasone in hai has resulted in

decreased toxicity.


This schematic shows the catheter inserted into the gastroduodenal artery

for hepatic infusion


3. Systemic Does not improve survival following resection or ablation.

Leads to systemic & hepatic toxicity.

Usually not tolerated by the patients.

4. Chemoembolization Administration of intra-arterial chemotherapy f/b infusion

of one of a number of embolic agents such as degradable starch, gelatin powder pvc,

Best accepted use is for patients with unrespectable metasteses from characinoid or islet cell tumors.

5. Targeted therapy Cetuximab (monoclonal antibody to egf.

Bevacizumab (monoclonal antibody to vegf)


PORTAL VEIN EMBOLIZATION

If portal vein branch of particular segment is blocked it

leads to ipsilateral lobe atrophy & contralateral lobe

hypertrophy .

Lead to the concept initiating hypertrophy of segment

of liver that would remain following a major liver

resection.

Percutaneous approach is the standard technique for

portal vein embolization.

Studies shown that future liver volume increased from

19%-36% of total liver volume pre embolization to 31-

59% postembolization.


LIVER TRANSPLANTATION

Which could an option when resection could not be tolerated

owing to inadequate liver reserve, rarely is performed for

metastatic disease because of high risk of recurrence related to

immunosuppressant.

Valid Indications and New Operative Strategies

A patient with liver metastases limited to one segment without

extrahepatic dissemination is always a candidate for liver

resection. The challenge for hepatobiliary surgeons is to achieve

the necessary resources and strategies that allow the patients’

benefit.


Patients can be divided into four groups

1. Patients with a voluminous hepatic metastases in which resection leaves an insufficient amount of functional liver parenchyma.

2. Patients with bilobar metastases.

3. Patients with recurrence after resection.

4. Patients with a primary colorectal tumor and synchronous liver metastases.

Patients with a Voluminous Liver Metastases

Two alternative may be offered: Tumor downsizing with systemic or local chemotherapy, and hypertrophy of the future remaining liver (non-tumoral) by portal embolization.


Downsizing: the use of neoadjuvant chemotherapy

with 5-fluorouracyl, folinic acid and oxalyplatin,

achieved an adequate tumoral downsizing, with similar

results as those patients initially resectable.

Liver parenchyma (usually left lobe), surgeons look for

hypertrophy of the non-tumoral liver.

Portal Embolization: When resection is not viable due

to insufficient functional nce embolization is

performed, hypertrophy is evaluated 5-6 weeks after

the procedure. If the future remaining liver is >30%,

then hepatectomy can be performed.


Hepatectomy associated to resection and tumoral

destruction by local treatment: Here, the greater

lesions are resected and the lesser ones are destroyed

locally by either RFA or cryotherapy.

Two-stage Hepatectomy after neoadjuvant

chemotherapy: The goal is to achieve an adequate

downsizing of the tumor that allows for a resection in

a one-stage or two-stage procedure.


Patients with Recurrence after Resection

Surgery is the only curative option for these patients. It has been shown that patients with a liver recurrence isolated or associated with a resectable extrahepatic metastases, resection of all the tumoral tissue achieves an overall survival similar to patients without recurrence.

Patients with a Primary Colorectal Tumor and

Synchronous Metastases

Surgical strategies remain controversial. Those who favor

simultaneous resection, and those who oppose it, differ in

terms of oncological basis, immunological techniques and

patient comfort.


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Www.medicalppt.blogspot.com Dr. Mukesh PUBLISHED BY MAHARANI LAXMI BAI MEDICAL COLLEGE, JHANSI “MANAGEMENT OF LIVER SECONDARIES”