Role of Endoscopic Ultrasound Guided Fine Needle Aspiration of Portal Vein Thrombus in the Diagnosis and Staging of Hepatocellular Carcinoma
Phase: NA
Conditions: Portal Vein Thrombosis
Sponsor: Mansoura University

 
 
 
 
Official Study Title: Role of Endoscopic Ultrasound Guided Fine Needle 
Aspiration of Portal Vein Thrombus in the Diagnosis and Staging of 
Hepatocellular Carcinoma. 
 
Document Title: Study Protocol. 
 
Document Date:   7th March 2019 

 
 
Introduction 
Portal vein thrombosis (PVT) is being increasingly diagnosed. It has a wide 
ranging clinical spectrum from being an asymptomatic state to a potentially life-
threatening situation. It is not unusual to find it as an incidental finding in the 
abdominal imaging done for other reasons. It is commonly associated with 
cirrhosis and abdominal malignancies and also has a strong association with 
prothrombotic disorders.  
A neoplastic thrombus of the portal vein is found in 6.5%–44% of patients with 
hepatocellular carcinoma (HCC). Bland (Non-malignant) thrombus occurs in 
patients with and those without malignant disease. Bland thrombus occurs in 
4.5%–26% of patients with chronic liver disease and in 42% of patients with HCC. 
In addition, bland and tumor thrombi can be coexistent. 
Presence of neoplastic thrombus serves as an important determinant of tumor 
staging, as well as prognosis, and influences treatment selection. In some cases, it 
may be even the initial sign of an undetected HCC.  Therefore, the detection of 
portal vein thrombus and accurate differentiation of bland from neoplastic 
thrombus are crucial for patient treatment.  
Portal vein tumor thrombosis (PVTT) on imaging studies appears as a low-
density plug within a dilated main or lobar portal vein. This plug enhances with 
contrast in the arterial phase on both CT and MRI and may have arterial signal on 
Doppler US. Non tumor portal vein thrombosis has a similar appearance to PVTT; 
however, it does not enhance with contrast nor does it have any Doppler signal. 
Therefore, whenever a PVT enhances with contrast or has a Doppler signal, PVTT 
remains the diagnosis until proved otherwise.  

 
 
Since not every PVT in a patient with HCC is a tumor thrombus, since the 
nature of the thrombus will ultimately determine the course of treatment, and since 
PVT may be even the initial sign of an undetected HCC, every effort should be 
made to distinguish between a tumor and a non-tumor PVT. In addition, malignant 
PVT does not always demonstrate neovascularity and/or enhancement, which 
makes FNA necessary in order to characterize the nature of the PVT.  
 Sampling of portal vein thrombus with trans-abdominal ultrasound guidance 
may lead to erroneous results because of inadvertent inclusion of normal 
hepatocytes or associated liver masses. Further, potential adverse events of trans-
abdominal PV sampling include serious biliary and/or vascular injury.  
In contrast to the percutaneous approach, EUS provides a unique view and 
access to the main portal vein. From the duodenal bulb and second part of the 
duodenum, the portal vein can be visualized from the confluence of the splenic and 
superior mesenteric veins into the porta hepatis. Periportal collateral vessels or 
cavernous transformation of the portal vein, which commonly are associated with 
portal vein thrombosis, are also easily and reliably detected by EUS instruments 
with color Doppler US capability approach. 
 With a linear-array echo-endoscope, the portal vein can be punctured easily 
with a fine needle under direct visualization, while avoiding the adjacent hepatic 
artery, bile duct, and collateral vessels (if present). Because the approach is not 
trans-hepatic, it eliminates any need to avoid the primary tumor and any possibility 
of contaminating the specimen with hepatocytes, as can occur if the needle tracks 
through the liver parenchyma. Thus, the rate of false-positive diagnoses is likely to 
be lower with the EUS compared with the percutaneous approach. 

 
 
Multiple case reports and case series have demonstrated the safety and efficacy 
of FNA of PVT. The vast majority of the published literature describes 
percutaneous US-guided FNA of a PVT, with only few reports noting the use of 
EUS-guided FNA. 
 
Aim of Work 
1) To assess the usefulness of using EUS-FNA in determining the percentage 
error in triphasic abdominal CT in the diagnosis of malignant portal vein 
thrombus. 
2) To assess the ease and safety of EUS-FNA as an invasive maneuver.  
Patients: 
Study Design: 
This is a pilot study that will include 30 patients with liver cirrhosis and portal 
vein thrombus which don’t fulfill the criteria of malignancy by imaging technique. 
The patients will be involved in the study will be admitted to Specialized Medical 
Hospital, Mansoura University Hospitals. 
Inclusion Criteria: 
 Patients with liver cirrhosis and PVT which don’t fulfill criteria of 
malignancy by triphasic CT abdomen  defined as, (neovascularity of thrombus, 
arterial enhancement with rapid washout, direct invasion by adjacent hepatic mass  
and diameter of thrombus more than 23 mm), either : 
 With or without hepatic mass  

 
 
 Undergone local treatment or surgical treatment following a diagnosis of 
HCC and develop PVT during their follow up.  
Exclusion criteria: 
 Uncooperative or excessively apprehensive patient 
 Anticoagulation treatment or non-substituted coagulopathy (International 
Normalized Ratio ≥ 1.5, Platelet count ≤ 50.000 cells/mm3, heparin administration 
at therapeutic doses). 
 Inhibition of platelet aggregation by clopidogrel and other thienopyridines. 
 Contraindications of sedation (Uncontrolled Diabetes Mellitus, Uncontrolled 
Thyroid Disorders, Pregnancy, Respiratory Embarrassment, Reactional Drugs like 
Antidepressants and Anti-anxiety Agents). 
 Patients fulfilling criteria of malignancy by triphasic CT on abdomen. 
  Extra hepatic metastasis of HCC. 
 Child-Pugh classification stage C.  
Study end-points: 
 24 months from the start of the research. 
Methods: 
Patients will be included in this study will be subjected to the following: 
І. The study will be explained to all participants in the study, and an informed 
written consent will be obtained from them before starting the study. 
ІІ. Medical history: 
Detailed history was taken with stress on: 

 
 
 Signs of cachexia (unintentional weight loss, progressive muscle wasting, 
and a loss of appetite) 
 Low grade fever 
 Recent onset fatigue 
 Abdominal pain 
 Dyspepsia 
 Hematemesis and melena 
 Back ache 
ІІІ. Full clinical examination with special stress on: 
 Vital signs including: pulse, arterial blood pressure, temperature, respiratory 
rate. 
 Abdominal Lumps and/or tenderness 
IV. Laboratory investigations: 
Complete blood count, International Normalized Ratio, Liver enzymes, Serum 
albumin, Serum bilirubin and Serum creatinine. 
V. Radiology: Abdominal ultrasound for initial assessment, Abdominal CT 
(Contrast Enhanced) (Number of HCC nodules if present, diameter of largest HCC 
nodule in centimeters, nature of PVT, presence of abdominal metastases if present 
), Non contrast CT chest to exclude pulmonary metastasis, Bone survey to exclude 
bone infiltrates. 
VI. EUS-FNA: 
              EUS-FNA will be performed in standard fashion. Under EUS 
guidance, the main, left and right portal veins will be identified. After verifying 

 
 
flow signal by Doppler, a 25-gauge EUS-FNA needle will be advanced from the 
duodenal bulb or second part of the duodenum into the portal vein, 1-2 passes 
through portal vein thrombus will be taken to ensure adequate cellularity for 
histopathology. The puncture site will be monitored under EUS for complications.  
 
Study outcomes: 
Histopathology of biopsies taken from bland portal vein thrombus which 
diagnosed by triphasic CT abdomen to evaluate the possibility of malignant PVT 
that was not discovered by imaging technique (Abdominal ultrasound and triphasic  
abdominal CT ).  
 
 
 
Sample size: 
One of the goals of a pilot study is to identify unforeseen problems. 
Malignant PVT may be an unforeseen problem in patients with liver cirrhosis 
and / or HCC if not detected by imaging modalities. 
This small-scale pilot study will examine the practicality and feasibility of EUS 
in diagnosing malignant PVT not detected by imaging studies. 
With a prevalence of 10%, malignant PVT not detected by imaging studies will 
almost certainly be identified by EUS (with 95% confidence) in a pilot study 
including 30 participants. 
This sample size was calculated by the following formula1: 
         
        
Where, 
  = Sample size of the pilot study. 

 
 
ln = Natural logarithm. 
  = Confidence level (chosen as 0.95) 
  = probability (chosen as 0.10) 
The result was 28.4 rounded to 29 participants.