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{{CMG}}; {{AE}} {{SH}}
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== Overview ==
== Overview ==
Hepatocellular carcinoma is best diagnosed on a core [[biopsy]] to confirm the [[diagnosis]]. Core [[biopsy]] is done in a single visit at the hospital.
Hepatocellular carcinoma is best diagnosed on a core [[biopsy]] of the [[liver]]. Core [[biopsy]] is done in a single visit at the hospital.


== Diagnostic Study of Choice ==
== Diagnostic Study of Choice ==


'''Liver biopsy'''
'''Liver biopsy'''
* The [[diagnosis]] of hepatocellular carcinoma is confirmed by [[percutaneous]] [[biopsy]] and [[histopathologic]] analysis. 
* [[Percutaneous]] [[biopsy]] should only be performed when [[Diagnosis|diagnostic]] imaging results are uncertain.


The [[diagnosis]] of hepatocellular carcinoma is confirmed by [[percutaneous]] [[biopsy]] and [[histopathologic]] analysis. [[Percutaneous]] [[biopsy]] should only be performed when [[Diagnosis|diagnostic]] imaging results are uncertain.
* [[Percutaneous]] core [[liver]] [[biopsy]] is the [[Gold standard (test)|gold standard test]] for the [[diagnosis]] of hepatocellular carcinoma.
* [[Percutaneous]] core [[liver]] [[biopsy]] is the [[Gold standard (test)|gold standard test]] for the [[diagnosis]] of hepatocellular carcinoma.
* In addition to the percutaneous approach, there are various other approaches to obtain a sample of the hepatic tissue, such as:<ref name="pmid16636018">{{cite journal |vauthors=Cholongitas E, Quaglia A, Samonakis D, Senzolo M, Triantos C, Patch D, Leandro G, Dhillon AP, Burroughs AK |title=Transjugular liver biopsy: how good is it for accurate histological interpretation? |journal=Gut |volume=55 |issue=12 |pages=1789–94 |year=2006 |pmid=16636018 |pmc=1856467 |doi=10.1136/gut.2005.090415 |url=}}</ref><ref name="pmid14562197">{{cite journal |vauthors=Hollerbach S, Reiser M, Topalidis T, König M, Schmiegel W |title=Diagnosis of hepatocellular carcinoma (HCC) in a high-risk patient by using transgastric EUS-guided fine-needle biopsy (EUS-FNA) |journal=Z Gastroenterol |volume=41 |issue=10 |pages=995–8 |year=2003 |pmid=14562197 |doi=10.1055/s-2003-42920 |url=}}</ref><ref name="pmid21291633">{{cite journal |vauthors=Wang L, Geng J, Li J, Li T, Matsumori A, Chang Y, Lu F, Zhuang H |title=The biomarker N-terminal pro-brain natriuretic peptide and liver diseases |journal=Clin Invest Med |volume=34 |issue=1 |pages=E30–7 |year=2011 |pmid=21291633 |doi= |url=}}</ref>
* In addition to the percutaneous approach, there are various other approaches to obtain a sample of the hepatic tissue, such as:<ref name="pmid16636018">{{cite journal |vauthors=Cholongitas E, Quaglia A, Samonakis D, Senzolo M, Triantos C, Patch D, Leandro G, Dhillon AP, Burroughs AK |title=Transjugular liver biopsy: how good is it for accurate histological interpretation? |journal=Gut |volume=55 |issue=12 |pages=1789–94 |year=2006 |pmid=16636018 |pmc=1856467 |doi=10.1136/gut.2005.090415 |url=}}</ref><ref name="pmid14562197">{{cite journal |vauthors=Hollerbach S, Reiser M, Topalidis T, König M, Schmiegel W |title=Diagnosis of hepatocellular carcinoma (HCC) in a high-risk patient by using transgastric EUS-guided fine-needle biopsy (EUS-FNA) |journal=Z Gastroenterol |volume=41 |issue=10 |pages=995–8 |year=2003 |pmid=14562197 |doi=10.1055/s-2003-42920 |url=}}</ref><ref name="pmid21291633">{{cite journal |vauthors=Wang L, Geng J, Li J, Li T, Matsumori A, Chang Y, Lu F, Zhuang H |title=The biomarker N-terminal pro-brain natriuretic peptide and liver diseases |journal=Clin Invest Med |volume=34 |issue=1 |pages=E30–7 |year=2011 |pmid=21291633 |doi= |url=}}</ref>
**Transjugular approach
**[[Transjugular intrahepatic portosystemic shunt|Transjugular]] approach
**[[Laparoscopic surgery|Laparoscopic]] radiographically- guided fine-needle approach
**[[Laparoscopic surgery|Laparoscopic]] radiographically guided fine-needle approach
**[[Endoscopic ultrasound]] ([[Endoscopic ultrasound|EUS]])-guided [[Fine-needle aspiration|fine-needle biopsy]] ([[Endoscopic ultrasound|EUS]]-[[Needle aspiration biopsy|FNA]])
**[[Endoscopic ultrasound]] ([[Endoscopic ultrasound|EUS]])-guided [[Fine-needle aspiration|fine-needle biopsy]] ([[Endoscopic ultrasound|EUS]]-[[Needle aspiration biopsy|FNA]])
* [[Percutaneous]] [[biopsy]] of focal lesions may be performed in combination with either [[ultrasound]] or [[CT|CT imaging]].<ref name="pmid15278290">{{cite journal |vauthors=Schirmacher P, Fleig WE, Tannapfel A, Langner C, Dries V, Terracciano L, Denk H, Dienes HP |title=[Bioptic diagnosis of chronic hepatitis. Results of an evidence-based consensus conference of the German Society of Pathology, of the German Society for Digestive and Metabolic Diseases and of Compensated Hepatitis (HepNet)] |language=German |journal=Pathologe |volume=25 |issue=5 |pages=337–48 |year=2004 |pmid=15278290 |doi=10.1007/s00292-004-0692-7 |url=}}</ref>  
* [[Percutaneous]] [[biopsy]] of focal lesions may be performed in combination with either [[ultrasound]] or [[CT|CT imaging]].<ref name="pmid15278290">{{cite journal |vauthors=Schirmacher P, Fleig WE, Tannapfel A, Langner C, Dries V, Terracciano L, Denk H, Dienes HP |title=[Bioptic diagnosis of chronic hepatitis. Results of an evidence-based consensus conference of the German Society of Pathology, of the German Society for Digestive and Metabolic Diseases and of Compensated Hepatitis (HepNet)] |language=German |journal=Pathologe |volume=25 |issue=5 |pages=337–48 |year=2004 |pmid=15278290 |doi=10.1007/s00292-004-0692-7 |url=}}</ref>  
* [[Percutaneous]] [[liver biopsy]] remains the cornerstone of [[diagnosis]]. It is quick and simple to perform [[liver biopsy]] in a patient with normal [[Platelet|platelet count]] and [[Prothrombin time|INR]].<ref name="pmid22833761">{{cite journal |vauthors=Tannapfel A, Dienes HP, Lohse AW |title=The indications for liver biopsy |journal=Dtsch Arztebl Int |volume=109 |issue=27-28 |pages=477–83 |year=2012 |pmid=22833761 |pmc=3402072 |doi=10.3238/arztebl.2012.0477 |url=}}</ref>  
* [[Percutaneous]] [[liver biopsy]] remains the cornerstone of [[diagnosis]]. It is a quick and simple to perform [[liver biopsy]] in a patient with normal [[Platelet|platelet count]] and [[Prothrombin time|INR]].<ref name="pmid22833761">{{cite journal |vauthors=Tannapfel A, Dienes HP, Lohse AW |title=The indications for liver biopsy |journal=Dtsch Arztebl Int |volume=109 |issue=27-28 |pages=477–83 |year=2012 |pmid=22833761 |pmc=3402072 |doi=10.3238/arztebl.2012.0477 |url=}}</ref>  
*Surgical resection
*Surgical resection
* Two out of the following three positive stains upon liver biopsy confirm HCC:<ref name="pmid19177576">{{cite journal |vauthors= |title=Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia |journal=Hepatology |volume=49 |issue=2 |pages=658–64 |year=2009 |pmid=19177576 |doi=10.1002/hep.22709 |url=}}</ref><ref name="pmid20400233">{{cite journal |vauthors=Karabork A, Kaygusuz G, Ekinci C |title=The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma |journal=Pathol. Res. Pract. |volume=206 |issue=8 |pages=572–7 |year=2010 |pmid=20400233 |doi=10.1016/j.prp.2010.03.004 |url=}}</ref>
* Two out of the following three positive stains upon liver biopsy confirm HCC:<ref name="pmid19177576">{{cite journal |vauthors= |title=Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia |journal=Hepatology |volume=49 |issue=2 |pages=658–64 |year=2009 |pmid=19177576 |doi=10.1002/hep.22709 |url=}}</ref><ref name="pmid20400233">{{cite journal |vauthors=Karabork A, Kaygusuz G, Ekinci C |title=The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma |journal=Pathol. Res. Pract. |volume=206 |issue=8 |pages=572–7 |year=2010 |pmid=20400233 |doi=10.1016/j.prp.2010.03.004 |url=}}</ref>
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'''Hep Par 1 Antibody Stain'''
'''Hep Par 1 Antibody Stain'''
Tissue [[microarray technology]] is uses to test Hep Par 1 [[antibody]] [[stain]] which is showing promising results in differential diagnosis of HCC.<ref name="Fanvan de Rijn2003">{{cite journal|last1=Fan|first1=Zhen|last2=van de Rijn|first2=Matt|last3=Montgomery|first3=Kelli|last4=Rouse|first4=Robert V.|title=Hep Par 1 Antibody Stain for the Differential Diagnosis of Hepatocellular Carcinoma: 676 Tumors Tested Using Tissue Microarrays and Conventional Tissue Sections|journal=Modern Pathology|volume=16|issue=2|year=2003|pages=137–144|issn=0893-3952|doi=10.1097/01.MP.0000052103.13730.20}}</ref>
* Tissue [[microarray technology]] is uses to test Hep Par 1 [[antibody]] [[stain]] which is showing promising results in differential diagnosis of HCC.<ref name="Fanvan de Rijn2003">{{cite journal|last1=Fan|first1=Zhen|last2=van de Rijn|first2=Matt|last3=Montgomery|first3=Kelli|last4=Rouse|first4=Robert V.|title=Hep Par 1 Antibody Stain for the Differential Diagnosis of Hepatocellular Carcinoma: 676 Tumors Tested Using Tissue Microarrays and Conventional Tissue Sections|journal=Modern Pathology|volume=16|issue=2|year=2003|pages=137–144|issn=0893-3952|doi=10.1097/01.MP.0000052103.13730.20}}</ref>


* A [[biopsy]] is not necessary if the [[clinical]], [[Medical laboratory|laboratory]], and [[Radiologic sign|radiologic]] data suggest hepatocellular carcinoma.
* A [[biopsy]] is not necessary if the [[clinical]], [[Medical laboratory|laboratory]], and [[Radiologic sign|radiologic]] data suggest hepatocellular carcinoma.
* [[Liver biopsy]] may be suggestive of [[etiology]]:
* [[Liver biopsy]] may be suggestive of [[etiology]] as the following:  
** [[Alcoholic liver disease]] : [[Liver biopsy]] may show [[hepatocyte]] [[necrosis]], presence of [[Mallory body|mallory bodies]], [[Neutrophil|neutrophilic]] infiltration and perivenular [[inflammation]].  
** [[Alcoholic liver disease]] : [[Liver biopsy]] may show [[hepatocyte]] [[necrosis]], presence of [[Mallory body|mallory bodies]], [[Neutrophil|neutrophilic]] infiltration and perivenular [[inflammation]].  
** [[Primary biliary cirrhosis|Primary biliary cirrhosis]] : [[Gold standard (test)|Gold standard diagnostic modality]] is the detection of [[antimitochondrial antibodies]] along with [[liver biopsy]] as confirmation of florid [[bile duct]] lesions.
** [[Primary biliary cirrhosis|Primary biliary cirrhosis]] : [[Gold standard (test)|Gold standard diagnostic modality]] is the detection of [[antimitochondrial antibodies]] along with [[liver biopsy]] as confirmation of florid [[bile duct]] lesions.
* There is a small but significant risk associated with [[liver biopsy]], and the underlying [[cirrhosis]] in the patients with HCC itself predisposes to complications due to [[liver biopsy]].<ref>{{cite journal |last=Grant |first=A|year=1999 | title=Guidelines on the use of liver biopsy in clinical practice |journal=Gut |volume=45 |issue=Suppl 4 |pages=1-11 |id=PMID 10485854 |url=http://gut.bmj.com/cgi/content/full/45/suppl_4/IV1|quote=The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68,000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding. }}</ref>   
* There is a small but significant risk associated with [[liver biopsy]], and the underlying [[cirrhosis]] in the patients with HCC itself predisposes to complications due to [[liver biopsy]].<ref>{{cite journal |last=Grant |first=A|year=1999 | title=Guidelines on the use of liver biopsy in clinical practice |journal=Gut |volume=45 |issue=Suppl 4 |pages=1-11 |id=PMID 10485854 |url=http://gut.bmj.com/cgi/content/full/45/suppl_4/IV1|quote=The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68,000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding. }}</ref>   
*Risks of [[liver biopsy]] include:
*There is a 3% risk of tumor spread in the [[percutaneous]] needle path, risks of [[liver biopsy]] include:<ref name="pmid22047762">{{cite journal |vauthors=Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A |title=Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report |journal=Lancet Oncol. |volume=13 |issue=1 |pages=e11–22 |year=2012 |pmid=22047762 |pmc=3417764 |doi=10.1016/S1470-2045(11)70175-9 |url=}}</ref>
**[[Bleeding|Hemorrhage]]
 
**[[Bile duct|Biliary]] [[peritonitis]]
*[[Bleeding|Hemorrhage]]
**[[Hematoma]]
*[[Bile duct|Biliary]] [[peritonitis]]
**[[Perforation]] of other [[Viscus|viscera]]
*[[Hematoma]]
**[[Mortality rate|Mortality rates]] of between 0.01% and 0.1%
*[[Perforation]] of other [[Viscus|viscera]]
*[[Mortality rate|Mortality rates]] of between 0.01% and 0.1%


* Patients with moderate [[coagulopathy]]: 
* Patients with moderate [[coagulopathy]]: 
Line 42: Line 44:
**[[Laparoscopic surgery|Laparoscopic]] [[liver biopsy]] performed on a sedated patient with moderate [[coagulopathy]]
**[[Laparoscopic surgery|Laparoscopic]] [[liver biopsy]] performed on a sedated patient with moderate [[coagulopathy]]
***Advantage:  
***Advantage:  
****Allows direct visualisation of the [[liver]]
****Allows direct visualization of the [[liver]]
'''Transjugular [[liver biopsy]]:'''
'''Transjugular [[liver biopsy]]:'''
* Used in patients with severe clotting disorders
* Used in patients with severe [[clotting]] disorders
**Advantage:
**Advantage:
***Risk of [[Peritoneum|intraperitoneal]] [[Bleeding|bleed]] is less
***Risk of [[Peritoneum|intraperitoneal]] [[Bleeding|bleed]] is less
Line 70: Line 72:
The core needle biopsy should be performed when:<ref name="pmid23091805">{{cite journal |vauthors=Song DS, Bae SH |title=Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period |journal=Clin Mol Hepatol |volume=18 |issue=3 |pages=258–67 |year=2012 |pmid=23091805 |pmc=3467428 |doi=10.3350/cmh.2012.18.3.258 |url=}}</ref>
The core needle biopsy should be performed when:<ref name="pmid23091805">{{cite journal |vauthors=Song DS, Bae SH |title=Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period |journal=Clin Mol Hepatol |volume=18 |issue=3 |pages=258–67 |year=2012 |pmid=23091805 |pmc=3467428 |doi=10.3350/cmh.2012.18.3.258 |url=}}</ref>
* A positive hepatic leision is detected in the patient on imaging studies.
* A positive hepatic leision is detected in the patient on imaging studies.
* The patient has underlying risk factors i.e HBV infection,HCV infection or liver cirrhosis.
* The patient has underlying risk factors i.e [[HBV infection]], [[HCV infection]] or [[liver cirrhosis]].
=== Diagnostic Criteria ===
=== Diagnostic Criteria ===
* Hepatocellular carcinoma may be diagnosed at any time if the following criteria is met:  
* Hepatocellular carcinoma may be diagnosed at any time if the following criteria is met:  
Line 78: Line 80:
***[[Glutamine synthetase]]
***[[Glutamine synthetase]]


==References==
=== Staging of hepatocellular carcinoma ===
According to the TNM staging system, there are four stages of hepatocellular carcinoma based on the tumor size, lymph node involvement, and distant metastasis.Although the TNM staging system is widely used for the staging of hepatocellular carcinoma, the Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that involves cirrhosis into account.<ref name="cancerca">Canadian Cancer Society.http://www.cancer.ca/en/cancer-information/cancer-type/liver/staging/?region=ab</ref>
===Primary tumor===
{| {{table}} cellpadding="4" cellspacing="0" style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;"
||TX
||Primary tumour cannot be assessed
|-
|T0||No evidence of primary tumour
|-
|T1||A single tumour with no invasion into the blood vessels of the liver
|-
|T2||A single tumour with invasion into the blood vessels or multiple tumours, none more than 5 cm in size
|-
|T3a||Multiple tumours, with any tumour larger than 5 cm
|-
|T3b||The tumour has grown into either the portal or hepatic vein
|-
|T4||The tumour has grown into nearby organs (other than the gallbladder) or the tumour has grown into the layer of tissue that covers the organs in the abdomen (visceral peritoneum)
|}
===Regional lymph node===
{| {{table}} cellpadding="4" cellspacing="0" style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;"
|NX||Regional lymph nodes cannot be assessed
|-
|N0||No regional lymph node metastasis
|-
|N1||Regional lymph node metastasis
|}
===Distance metastasis===
{| {{table}} cellpadding="4" cellspacing="0" style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;"
|M0||No distant metastasis
|-
|M1||Distant metastasis
|}
===Clip and Okuda Staging Systems for Hepatocellular Carcinoma===
Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that involves cirrhosis into account.<ref>{{cite book | last = Kasper | first = Dennis | title = Harrison's principles of internal medicine | publisher = McGraw Hill Education | location = New York | isbn = 978-0-07-1802161 }}</ref>
 
'''CLIP Classification'''
{| class="wikitable"
!
! colspan="3" |Points
|-
|'''Variable'''
|0
|1
|2
|-
|[[Tumor|i.Tumor]] number (%)
|Single
|Multiple
|–
|-
|Hepatic replacement by tumor
|<50
|<50
|>50
|-
|ii. [[Child-Pugh score]]
|A
|B
|C
|-
|iii. α Fetoprotein level (ng/mL)
|<400
|≥400
|–
|-
|iv.[[Portal vein thrombosis]] (CT)
|No
|Yes
|–
|-
| colspan="4" |CLIP stages (score = sum of points): CLIP 0, 0 points; CLIP 1, 1 point; CLIP 2, 2 points; CLIP 3, more than 3
points.
|}'''OKUDA'''  '''Classification'''
{| class="wikitable"
| colspan="8" style="background:#4479BA; color: #FFFFFF;" align="center" |'''OKUDA Classification'''
|-
| colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |'''Tumor Extent*'''
| colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |'''Bilirubin (mg/dL)'''
| colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |'''Albumin (g/L)'''
| colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |'''Ascites'''
|-
|≥50%
|<50
|≥ 3
|<3
|≤3
|>3
| +
|–
|-
|(+)
|(−)
|(+)
|(−)
|(+)
|(−)
|(+)
|(−)
|-
| colspan="8" |Okuda stages: stage 1, all (−); stage 2, 1 or 2 (+); stage 3, 3 or 4 (+).
|}
 
== References ==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WH}}
{{WS}}
{{WS}}
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[[Category:Emergency medicine]]

Latest revision as of 22:07, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]

Overview

Hepatocellular carcinoma is best diagnosed on a core biopsy of the liver. Core biopsy is done in a single visit at the hospital.

Diagnostic Study of Choice

Liver biopsy

Hep Par 1 Antibody Stain

Transjugular liver biopsy:

The comparison table for diagnostic studies of choice for hepatocellular carcinoma:[11]

Diagnostic Test Sensitivity Specificity
Percutaneous Ultrasound guided liver biopsy 90% 91%
Percutaneous CT guided liver biopsy 92% 98%
Sequence of Diagnostic Studies

The core needle biopsy should be performed when:[12]

Diagnostic Criteria

Staging of hepatocellular carcinoma

According to the TNM staging system, there are four stages of hepatocellular carcinoma based on the tumor size, lymph node involvement, and distant metastasis.Although the TNM staging system is widely used for the staging of hepatocellular carcinoma, the Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that involves cirrhosis into account.[14]

Primary tumor

TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 A single tumour with no invasion into the blood vessels of the liver
T2 A single tumour with invasion into the blood vessels or multiple tumours, none more than 5 cm in size
T3a Multiple tumours, with any tumour larger than 5 cm
T3b The tumour has grown into either the portal or hepatic vein
T4 The tumour has grown into nearby organs (other than the gallbladder) or the tumour has grown into the layer of tissue that covers the organs in the abdomen (visceral peritoneum)

Regional lymph node

NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis

Distance metastasis

M0 No distant metastasis
M1 Distant metastasis

Clip and Okuda Staging Systems for Hepatocellular Carcinoma

Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that involves cirrhosis into account.[15]

CLIP Classification

Points
Variable 0 1 2
i.Tumor number (%) Single Multiple –
Hepatic replacement by tumor <50 <50 >50
ii. Child-Pugh score A B C
iii. α Fetoprotein level (ng/mL) <400 ≥400 –
iv.Portal vein thrombosis (CT) No Yes –
CLIP stages (score = sum of points): CLIP 0, 0 points; CLIP 1, 1 point; CLIP 2, 2 points; CLIP 3, more than 3

points.

OKUDA Classification

OKUDA Classification
Tumor Extent* Bilirubin (mg/dL) Albumin (g/L) Ascites
≥50% <50 ≥ 3 <3 ≤3 >3 + –
(+) (−) (+) (−) (+) (−) (+) (−)
Okuda stages: stage 1, all (−); stage 2, 1 or 2 (+); stage 3, 3 or 4 (+).

References

  1. ↑ Cholongitas E, Quaglia A, Samonakis D, Senzolo M, Triantos C, Patch D, Leandro G, Dhillon AP, Burroughs AK (2006). "Transjugular liver biopsy: how good is it for accurate histological interpretation?". Gut. 55 (12): 1789–94. doi:10.1136/gut.2005.090415. PMC 1856467. PMID 16636018.
  2. ↑ Hollerbach S, Reiser M, Topalidis T, König M, Schmiegel W (2003). "Diagnosis of hepatocellular carcinoma (HCC) in a high-risk patient by using transgastric EUS-guided fine-needle biopsy (EUS-FNA)". Z Gastroenterol. 41 (10): 995–8. doi:10.1055/s-2003-42920. PMID 14562197.
  3. ↑ Wang L, Geng J, Li J, Li T, Matsumori A, Chang Y, Lu F, Zhuang H (2011). "The biomarker N-terminal pro-brain natriuretic peptide and liver diseases". Clin Invest Med. 34 (1): E30–7. PMID 21291633.
  4. ↑ Schirmacher P, Fleig WE, Tannapfel A, Langner C, Dries V, Terracciano L, Denk H, Dienes HP (2004). "[Bioptic diagnosis of chronic hepatitis. Results of an evidence-based consensus conference of the German Society of Pathology, of the German Society for Digestive and Metabolic Diseases and of Compensated Hepatitis (HepNet)]". Pathologe (in German). 25 (5): 337–48. doi:10.1007/s00292-004-0692-7. PMID 15278290.
  5. ↑ Tannapfel A, Dienes HP, Lohse AW (2012). "The indications for liver biopsy". Dtsch Arztebl Int. 109 (27–28): 477–83. doi:10.3238/arztebl.2012.0477. PMC 3402072. PMID 22833761.
  6. ↑ 6.0 6.1 "Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia". Hepatology. 49 (2): 658–64. 2009. doi:10.1002/hep.22709. PMID 19177576.
  7. ↑ Karabork A, Kaygusuz G, Ekinci C (2010). "The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma". Pathol. Res. Pract. 206 (8): 572–7. doi:10.1016/j.prp.2010.03.004. PMID 20400233.
  8. ↑ Fan, Zhen; van de Rijn, Matt; Montgomery, Kelli; Rouse, Robert V. (2003). "Hep Par 1 Antibody Stain for the Differential Diagnosis of Hepatocellular Carcinoma: 676 Tumors Tested Using Tissue Microarrays and Conventional Tissue Sections". Modern Pathology. 16 (2): 137–144. doi:10.1097/01.MP.0000052103.13730.20. ISSN 0893-3952.
  9. ↑ Grant, A (1999). "Guidelines on the use of liver biopsy in clinical practice". Gut. 45 (Suppl 4): 1–11. PMID 10485854. The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68,000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding.
  10. ↑ Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A (2012). "Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report". Lancet Oncol. 13 (1): e11–22. doi:10.1016/S1470-2045(11)70175-9. PMC 3417764. PMID 22047762.
  11. ↑ El-Serag HB, Marrero JA, Rudolph L, Reddy KR (2008). "Diagnosis and treatment of hepatocellular carcinoma". Gastroenterology. 134 (6): 1752–63. doi:10.1053/j.gastro.2008.02.090. PMID 18471552.
  12. ↑ Song DS, Bae SH (2012). "Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period". Clin Mol Hepatol. 18 (3): 258–67. doi:10.3350/cmh.2012.18.3.258. PMC 3467428. PMID 23091805.
  13. ↑ Di Tommaso L, Roncalli M (2017). "Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How". Front Med (Lausanne). 4: 10. doi:10.3389/fmed.2017.00010. PMC 5322593. PMID 28280721.
  14. ↑ Canadian Cancer Society.http://www.cancer.ca/en/cancer-information/cancer-type/liver/staging/?region=ab
  15. ↑ Kasper, Dennis. Harrison's principles of internal medicine. New York: McGraw Hill Education. ISBN 978-0-07-1802161.

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