Role of EUS Guided FNA of Portal Vein Thrombus in the Diagnosis and Staging of Hepatocellular Carcinoma

Role of Endoscopic Ultrasound Guided Fine Needle Aspiration of Portal Vein Thrombus in the Diagnosis and Staging of Hepatocellular Carcinoma

Since not every portal vein thrombus (PVT) in a patient with hepatocellular carcinoma (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 fine needle aspiration (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 portal vein sampling include serious biliary and/or vascular injury.

In contrast to the percutaneous approach, Endoscopic ultrasound (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.

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

This is a pilot study that include 30 patients with liver cirrhosis and portal vein thrombus which don't fulfill the criteria of malignancy by imaging technique. The patients involved in the study were and will be admitted to Specialized Medical Hospital, Mansoura University Hospitals.

Study end-points:

• 24 months from the start of the research (cases will be collected over 18 months).

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 for indicated or complaining cases.

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 ).

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.