Utility and Safety of EUS-guided Portal Vein FNA. (2011)

Hepatocellular carcinoma (HCC) is a fatal complication of cirrhosis; however, recent treatment advancements, including liver transplantation in select cases, have made HCC a potentially curable disease. Curative treatment options are attempted only in the absence of extensive vascular invasion or extrahepatic spread. The diagnosis of HCC is usually established by radiologic imaging, as the laboratory tests currently available have inadequate sensitivity or specificity. However, an elevated alpha-fetoprotein (AFP) level (>200 ng/mL), or a rising AFP level, in the presence of a mass on imaging has a very high positive predictive value for the diagnosis of HCC. Similarly, a significant elevation in AFP level (>1,000 ng/mL), in the absence of a testicular tumor, is highly suggestive of an occult HCC, particularly in the presence of cirrhosis, even in the absence of a visible lesion on sensitive imaging modalities, such as triple-phase computed tomography (CT) scan or contrast-enhanced magnetic resonance imaging (MRI). For this reason, AFP is still used in many centers as a complementary test for both surveillance and diagnosis of HCC, despite its limitations.

Imaging modalities, such as transabdominal ultrasound (TA-US), CT scan, or MRI, have variable sensitivities and specificities for the diagnosis of HCC in patients with cirrhosis, depending on the technique and expertise of the operator and radiologist. Our group has previously evaluated the potential role and limitations of endoscopic ultrasound (EUS) for the diagnosis of HCC.1,2 Based upon the published data, we have suggested that EUS and EUS-guided fine-needle aspiration (FNA) may be particularly useful in the management of a subset of patients with small liver lesions that are difficult to sample via traditional TA-US and lesions located in liver segments that can be adequately visualized by EUS.

The case report presented by Michael and associates illustrates the difficulties of diagnosing and staging HCC in the absence of a clearly defined primary liver mass.3 The patient described in this case report had no clinical signs or history of chronic liver disease and presented with a markedly elevated AFP level (1,448 ng/mL). His CT scan showed cirrhosis and a dilated, thrombosed portal vein (PV). There was no obvious liver mass on the CT scan, but there was arterial enhancement of a PV thrombus, raising a strong suspicion of a tumor thrombus. The diagnosis was made through EUS-guided FNA of the PV thrombus, which revealed a poorly differentiated HCC.

As Michael and coworkers pointed out, PV thrombosis (PVT) is a common finding in patients with advanced cirrhosis, due to either sluggish or turbulent blood flow and/or clotting abnormalities.3 Tumor thrombus, unlike nontumor PVT, shows arterial enhancement on CT or MRI. The diagnosis of a tumor thrombus is relatively easy when patients present with a liver mass suggestive of HCC and PV thrombus that enhances on arterial phase of CT or MRI. However, the diagnosis of tumor thrombosis is difficult in the absence of a discrete or infiltrating liver mass or when there is nondiagnostic elevation of AFP level or equivocal enhancement of tumor thrombus. When liver transplantation or a curative resection is planned, a firm diagnosis or exclusion of tumor thrombus becomes critically important.

This case report raises several clinically important issues, including the utility and safety of FNA of the PV.3 Earlier attempts at this procedure, performed under TA-US to diagnose suspected HCC thrombus, were reported from 1992 to 1997.4–12 These studies clearly demonstrated the effectiveness of FNA of the PV. In the largest reported series, only 6 aspirates (12.5%) were negative for malignancy, 39 aspirates were positive (81.3%), and 3 aspirates were suspicious for malignancy (6.2%).8 Despite the effectiveness and safety margins found in these reports, there was a paucity of published studies on TA-US–guided FNA of the PV after these initial publications. There could be many reasons why this highly effective and seemingly safe technique has not become a standard option in the diagnosis and staging of HCC in patients with suspected tumor thrombus of the PV. One reason could be the improvement in CT and MRI, which makes tissue sampling unnecessary in most patients. Another reason could be the technical difficulties of TA-US–guided aspiration in patients with cirrhosis, obesity, or ascites. Spatial resolution of the ultrasound beam is directly proportional to its frequency, but the penetrating ability of the ultrasound beam is inversely proportional to its frequency. During evaluation of the liver and PV with TA-US, the ultrasound beam has to travel at least 20–25 cm before reaching the PV. In this situation, only a relatively low frequency (3.5 mHz) ultrasound beam could be used, making evaluation and precise targeting of the PV difficult and thereby increasing the potential for complications (inadvertent injury to adjacent bile ducts, arterial vessels, and so on). In addition, during the percutaneous approach, the needle also has to travel a relatively long distance from the skin to the PV through a cirrhotic liver. Perhaps for all of these reasons, TA-US–guided FNA of the PV has not become more widely used.

In 2004, Lai and colleagues published the first case report of EUS-guided FNA of the PV for diagnosis of HCC, which was followed by a second report in 2007 by Storch and coworkers.13,14 EUS-guided FNA of the PV has undeniable advantages over TA-US. An echoendoscope can deliver the source of the ultrasound beam within 2–3 cm of the PV, uses high frequency (10–12 mHz) ultrasound, and provides excellent resolution and reliable visualization of the PV, its content, and surrounding tissue and organs. Moreover, the FNA needle has to travel only a short distance, making the procedure quick and precise. The case report presented by Michael and associates confirms the previous observations regarding the ease, safety, and efficacy of EUS-guided FNA for suspected tumor thrombus of the PV and strongly advocates its use for HCC diagnosis and staging.3

EUS-guided intravascular procedures have even more potential than aspiration of cytologic material from a thrombosed PV. Recent animal experiments and human studies have demonstrated successful use of EUS as a platform for various diagnostic and therapeutic intravascular interventions: EUS-guided angiography, PV catheterization and pressure measurements, and even EUS-guided creation of an intrahepatic portosystemic shunt and embolization of gastric varices (Figures 1 and 2).15–20 Although interventional EUS remains in an early stage of development, it could become a valuable clinical tool in the management of patients with cirrhosis, portal hypertension, HCC, and other liver diseases.



Figure 1

Endoscopic ultrasound–guided angiography of the portal vein.





Figure 2

Endoscopic ultrasound (EUS)-guided creation of an intrahepatic portosystemic shunt (arrow). The proximal end of the newly created shunt is inside the hepatic vein (HV), and the distal end is inside the portal vein (PV).



Although the 3 case reports describing EUS-guided FNA of a PVT demonstrated the efficacy and safety of the procedure, numerous technical questions remain unanswered: Could contamination of the FNA needle with gastric and/or duodenal cells lead to misinterpretation and false-positive results? Could the tumor spread through the FNA needle track? It could be argued that this risk is perhaps not clinically relevant in an individual with a tumor thrombus in the PV. Finally, and, most importantly, how high is the risk of bleeding after puncture of the thrombosed PV with an FNA needle? Carefully managed, large, prospective clinical studies are needed to answer all of these questions before EUS-guided FNA of the PVT can be recommended as a routine test in patients with HCC and suspected malignant PVT. Despite these concerns, we believe that EUS-guided FNA of the PV should be considered when a firm diagnosis or exclusion of PV tumor thrombus is critically important, as when curative options are potentially available.