Original papers
2010, Vol. 12, no. 4, 286-294Abstract
Aim: The ultrasonographic (US) detection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis is based on the visualization of focal lesions. However, in some cases HCC cannot be clearly identified at US, the only sign being a portal vein thrombosis (PVT). Contrast enhanced ultrasound (CEUS) is an excellent method to characterise focal lesions and portal thrombosis in patients with liver cirrhosis. The aim of the study was to assess the value of US and CEUS -guided PVT core biopsy in the diagnosis of an occult HCC in patients with cirrhosis.
Material and methods: Twenty patients with cirrhosis, PVT and no focal lesion on high-resolution US were studied. In 17 cases the thrombus was interpreted as malignant at US. All patients had normal coagulation parameters. The biopsies of an intrahepatic PVT were performed using an 18G Bard needle coupled on “Biopty Gun”.US and CEUS guidance was used in16 respectively 4 patients. In 10 cases with a very inhomo- geneous hepatic echostructure near the PVT (coarse echo pattern) a liver biopsy from that area was performed. Results: Adequate histological specimens were obtained in all cases, requiring 1 to 2 passes (mean 1.5 per patient). Only 1 patient had severe pain. No major complications were detected. The overall sensitivity of core biopsy in the diagnosis of malignant PVT was 94.4 % (17/18). The sensitivities of US and CEUS guided PVT biopsy were 92.8% (13/14) and 100% (4/4) respectively. In 6 of 10 cases with coarse echo pattern the same type of HCC was found in the surrounding parenchyma. No false positive results were noted. Conclusions: US-guided core biopsy of PVT is a safe and useful technique in the diagnosis of occult HCC in cirrhosis and should be performed in all cases with PVT with malignant US features and no evidence of fo- cal lesions. The “coarse echo pattern” found in the vicinity of a malignant thrombus is frequently the expression of an inapparent, occult HCC.
CEUS guided PVT biopsy is a new, promising method with excellent results in establishing the nature of a portal thrombus.
Key words: liver cirrhosis, portal vein thrombosis, hepatocellular carcinoma, percutaneous core needle biopsy, contrast enhanced ultra- sound guided biopsy
Rezumat
Scop: Diagnosticul ecografic (US) al hepatocarcinomului ( HCC) la pacienţii cu ciroză hepatică este bazat pe vizualizarea leziunilor focale. Totuşi în unele cazuri leziunile de HCC nu pot fi vizualizate ecografic, singurul semn de HCC în acest caz la o parte din aceşti pacienţi este tromboza de vena porta (TVP). Ecografia cu substanţă de contrast ( CEUS) este o metodă imagistică cu ajutorul căreia se pot caracteriza atât leziunile focale precum şi trombul portal la pacienţii cirotici. Scopul acestui studiu este evaluarea aportului pe care îl are biopsia trombului portal efectuată prin ghidaj US şi CEUS în diagnosticul HCC ocult la pacienţii cu ciroză hepatică. Material şi metodă: În studiu au fost incluşi 20 de pacienţi cu ciroză şi TVP fără leziuni focale hepatice vizibile ecografic. În 17 cazuri trombul a fost interpretat ca malign la examinarea US. Toţi pacienţi aveau probele de coagulare în limite acceptabile. S-a efectuat biopsia trombului portal cu un ac Bard 18 G cuplat la “Biopty Gun”. Ghidarea US respectiv CEUS a fost folosită la 16 respectiv 4 pacienţi. La 10 pacientţ, care prezentau o ecostructură foarte inomogena a parenchimul hepatic adiacent venei porte trombozate, s-a efectuat o biopsie hepatică de la acel nivel. Rezultate: La toţi pacienţii fragmentele bioptice recoltate au fost corespunzatoare, necesitand 1-2 paaje (medie 1,5). Un singur pacient a prezentat dureri severe post biopsie. Nu au fost semnalate complicaţii majore. Sensibilitatea globală, cea prin ghidare US şi ghidare CEUS a acestei metode a fost de 94,4% ( 17/18), 92,8% ( 13/14) respectiv 100% (4/4). La 6 din 10 cazuri care prezentau o ecostructură foarte inomogenă lângă vena portă trombozată, a fost identificat acelaşi tip de HCC în parenchim. Nu a fost semnalate rezultate fals pozitive. Concluzii: Biopsia trombului portal prin ghidare US este o metodă sigură şi foarte utilă în diagnosticul HCC ocult la pacienţii cirotici cu TVP cu caractere ecografice de malignitate. Aspectul foarte inomogen al parenchimului hepatic adiacent trombului malign este de cele mai multe ori expresia unui HCC inaparent. Ghidarea CEUS a biopsiei este o metodă noua, care promite obţinerea unor rezultate excelente în stabilirea naturii trombului portal.
Cuvinte cheie: ciroză hepatică, tromboză venă portă, carcinom hepatocelular, puncţie biopsie percutană cu ac gros, puncţie biopsie ghidată prin ecografie armonică cu contrast
B-mode and Contrast Enhanced Ultrasound guided biopsy of portal vein thrombosis. Value in the diagnosis of occult hepatocellular carci- noma in liver cirrhosis
Zeno Spârchez
1, Pompilia Radu
1, Teodor Zaharia
1, Gabriel Kacso
2, Brîndusa Diaconu
1, Ioana Grigorescu
1, Radu Badea
11 3rd Medical Clinic, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania
2 Oncological Institute, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania
Received 20.08.2010 Accepted 30.09.2010 Med Ultrason
2010, Vol. 12, No 4, 286-294
Address for correspondence: Assoc.Prof.Zeno Spârchez
3rd Medical Clinic, University of Medicine Croitorilor 19-21, Cluj Napoca, Romania Email:[email protected]
Introduction
Portal vein thrombosis (PVT) which occurs usually in liver cirrhosis [1–3] may be caused by both malignant and benign conditions. Malignant PVT is a usual com- plication of hepatocellular carcinoma (HCC) in cirrhosis and signifies an advanced tumoral stage [1]. Because the
prevalence of tumor recurrence is nearly 100%, patients who have HCC and proven neoplastic vascular thrombus are not candidates for any treatment.
In cirrhotic patients with HCC, PVT may have both malignant and benign causes. The presence of a PVT near an HCC usually signifies portal vein invasion;
meanwhile, a thrombus remote from a HCC treated by percutaneous ablation techniques such as ethanol injec- tion is in most cases a benign chemical thrombus. In a small percentage of patients, PVT may be the initial sign of an undetected, inapparent HCC which has an intravas- cular first growth [4].
Benign and malignant thrombi may not be easily distin- guishable by conventional imaging studies such as abdom- inal ultrasound (US), computed tomography (CT) and res- onance magnetic imaging so, in many cases a percutaneous fine needle aspiration biopsy is required to establish the diagnosis. In recent years contrast enhanced sonography (CEUS) has emerged as an excellent technique to charac- terise hepatic tumors and portal thrombosis [5,6]. Moreo- ver, some recent data suggest that CEUS may improve the accuracy of percutaneous US guided biopsies [6-8].
The aim of this study was to investigate the role of percutaneous US and CEUS guided core biopsy in the di- agnosis of PVT and to assess the value of this technique in the diagnosis of inapparent, occult HCC.
Patients and methods
From January 2000 to December 2009 20 patients with liver cirrhosis and portal vein thrombosis, 13 males and 7 females, aged from 41 to 72 years ( mean 58.5 years) were enrolled. All, except 2 patients with known HCC nodules treated by percutaneous ethanol injection remote from the present PVT, had no focal lesions on high resolution ultrasonography.
Based on US and color Doppler features of PVT ma- lignant PVT in 17 patients was suspected. None of them had ultrasound recognizable focal lesions. In 10 patients a very inhomogenous echostructure near the thrombus was noted (“coarse echo pattern).
As portal vein invasion precludes curative treatments (surgery, percutaneous ablative techniques) percutaneous biopsy was performed in order to certify the neoplastic nature of the thrombus and to initiate chemotherapy.
Equipment and procedures
B mode and color/Power Doppler Ultrasound.
Fifteen patients were examined with an Acuson 128XP machine equipped with a 3.5 MHz transducer. The last five patients were examined with a Logiq 7 machine
(General Electric, Milwaukee, USA) with real-time con- trast specific software and a 3-5 MHz convex array wide band probe. Baseline unenhanced color Doppler sono- graphic studies were performed using a low pulse repeti- tion frequency (750 to 1200 Hz) to optimize detection of weak signals. The color box was restricted as much as possible to maximize color sensitivity and frame rate.
PVT was diagnosed based on the characteristic B mode ultrasound findings which include an echogenic thrombus within the lumen of portal vein, lack of vizuali- zation of venous flow inside the vein, portal vein collat- erals and cavernous transformation [9,10]. Color/Power Doppler sonography was used to demonstrate either the absence of flow or the presence of flow circumventing a clot within the PV [11,12].
Malignant PVT was suspected in the case of expan- sion of the caliber of vein (fig 1), interruption of the PV wall and the presence of arterial flow inside the PV thrombus at pulsed Doppler sonography (fig 2).
Fig 1. Maligant PVT with expansion of the caliber of vein (ar- rowhead)
Fig 2. Malignant PVT. Presence of arterial flow inside the PV thrombus at pulsed Doppler sonography
The localization of PVT was: a) right or/and left PV but no main portal trunk (10 patients); b) main portal trunk and left and/or right PV (10 patients). PVT was complete in 15 patients and incomplete in 5.
Contrast enhanced ultrasound
Contrast enhanced imaging was performed according to the protocol used for the Bracco-SonoVue preclinical trial [13]. Examination was performed with low acous- tic power (mechanical index under 0.01) after injection of a SonoVue (BR1; Bracco, Milan, Italy). SonoVue consisted of sulfur-hexafluoride (SF6) vapor-filled and phospholipid-stabilized microbubbles with a diameter uniformly smaller than 8 μm; these microbubbles circu- late in the intravascular space crossing pulmonary and systemic capillary circulation. 2.4 mL of contrast-agent were administered for each patient. The low mechani- cal index technique avoids destruction of bubbles thus allowing to identify the entire vascular phase of contrast agent perfusion, consisting of the arterial phase (15-30 s after injection of agent), the portal phase (30-60 s after injection of agent) and the late parenchymal phase [5].
The diagnosis of PVT was based on the complete or partial absence of enhancement within the vessel lumen in the portal and late phases. A malignant thrombus was certified by the presence of enhancing tissue within the vessel lumen in the arterial phase (fig 3) [14]. Contrast enhanced ultrasonography (CEUS) were performed only in the last 4 patients.
Portal vein US guided thrombus biopsy
The biopsy was performed with a 1.2 mm (18G) Bard needle coupled on an automatic device (Biopty Gun).
Two sonographic systems (Acuson 128XP and Logiq 7) equipped with a 3.5 MHz sector probe and biopsy guide were used. The use of a probe with color Doppler facili- ties was useful to avoid the hepatic artery branches and other major vessels.
For thrombi in the left portal vein (6 patients), a sub- xyphoid approach was used, while for those in the right portal vein (14 patients), an intercostal or right subcostal approach was necessary. The coagulation studies accept- ed for the PVT biopsy were a platelets count higher than 60000/mmc and prothrombin time less than 15 sec.
After localization of an intrahepatic segment of the thrombosed portal vein, with color-Doppler mapping of the adjacent hepatic artery or other major vessels, we chose an appropiate biopsy path avoiding the vascular structures. PVT biopsy was performed with real-time sonographic guidance using 18 G cutting needles (Bard) coupled on a Biopty Gun. The needle has a 1.4 cm long sampling notch. Special care was taken to maintain the
Fig 3. Malignant thrombus. CEUS reveals enhancing tissue within the vessel lumen (arrowhead) in the arterial phase
Fig 4. US guided biopsy of a PVT
Fig 5. CEUS guided biopsy of an enhancing PVT. Note the presence of the needle inside the enhancing areas of the throm- bus
approved by the Ethical Committee of the 3rd Medical Clinic, Cluj-Napoca.
Results
A good histological specimen was sampled in 100%
of cases, with a mean 1.5 passages per patients (range 1-3). The mean length of the specimen sampled with US guidance from the thrombus was 1.16 cm (range 0.8-1.3 cm) and from liver parenchyma adjacent to the PVT 1.17 cm (range 0.8-1.4 cm) (difference not significant). With CEUS guidance the specimen had a mean length of 1.13 cm (range 1-1.2 cm).
The overall sensitivity of core biopsy in the diagnosis of malignant PVT was 94.4 % (17/18). US and CEUS guided PVT biopsy have a sensitivity of 92.8% (13/14) and 100% (4/4) respectively. The 2 cases with PVT re- mote from a treated HCC nodule had benign thrombosis due to the leakage of alcohol into the portal vein (chemi- cal thrombosis). The specificity for both methods was 100%.
In 6 out of 10 cases with an additional parenchymal biopsy adjacent to the PVT the diagnosis of HCC with a similar pattern was established (table I, fig 6).
There were no major complications. One patient ex- perienced severe pain after a PVT biopsy which ceased after administration of Tramadol.
needle within the lumen of PV at all times (fig 4) [15].
The mean diameter of the portal vein where the puncture was performed was 12.1 mm range 10-20 mm).
In 10 cases with a very inhomogeneous hepatic echostructure near the PVT (coarse echo pattern) an additional passage was performed from that area in the same session.
CEUS guided PVT biopsy was performed in 4 pa- tients with complete PVT with malignant features, no focal liver lesions and an inhomogenous enhancement of the PVT at CEUS. The puncture of the thrombus was performed in the arterial phase (or in the early portal phase) in an attempt to target the enhancing areas inside the thrombus (fig 5).
The tissue specimens were placed in 10% formal- dehyde for histological examination. Pathological diag- nosis of HCC was made according to the International Working Party criteria [16]. All patients were observed for 30 minutes after puncture and then sent to the gastro- enterological department. They remained in the hospital for the next 24 hours.
Ethical issues
All patients enrolled in the study gave their informed consent to participate. The protocol was submitted to and Table I. Results of PVT and parenchymal biopsy
Nr. Thrombus biopsy Adjacent parenchymal biopsy Observation
1. HCC medium/poor differentation HCC poor differentation 2. HCC medium differentation HCC medium differentation + cirrhosis
3. HCC poor dif difer. HCC poor differentation
4. HCC well/medium differentation HCC well/medium differ+ cirrhosis 5. HCC well/medium differentation HCC well/medium differ+ cirrhosis
6. HCC well differentation Cirrhosis
7. Non neoplastic thrombus Cirrhosis Severe PHT
8. Cholangiocarcinoma np Bile ducts invasion
9. Non neoplastic thrombus np Chemical thrombosis
10. Non neoplastic thrombus np Chemical thrombosis
11. HCC medium differentation Cirrhosis
12. HCC medium differentation Cirrhosis + dysplastic foci
13. HCC well differentation np
14. HCC poor differentation np
15. HCC medium differentation np
16. HCC well/medium differ np
17. HCC poor differentation np CEUS guided biopsy
18. HCC poor differentation np CEUS guided biopsy
19. HCC medium differentation Cirrhosis CEUS guided biopsy
20. HCC poor differentation np CEUS guided biopsy
HCC- hepatocellular carcinoma; PHT- portal hypertension, np-not performed
Discussion
Patients with liver cirrhosis have a greater risk of developing benign or malignant PVT than the general population [17]. It is a relative rare complication of liver cirrhosis, with 1-5.7% prevalence [2,3] and is caused by benign or malignant processes.
Concerning the benign causes, it is difficult to con- sider cirrhosis per se as a cause of PVT except in ter- minal cases with severe portal hypertension and venous stasis [3]. PVT occurring in patients without cancer and in good condition is usually associated with a prethrom- botic condition [3] and/or local factors such as infections (pancreatitis, cholecystitis, neonatal omphalitis a.o) and injury to the portal venous system such as surgical por- tocaval shunting and splenectomy. In recent years, an iatrogenic origin of PVT in cirrhosis has also emerged;
endoscopic sclerotherapy of esophageal varices and per- cutaneous ablation therapies (PATs) for HCC may pro- voke PVT [18-20].
Malignant PVT occurs by direct invasion of the por- tal vein by HCC, a common complication of liver cir- rhosis. Based upon autopsy data or imaging techniques, the incidence of PVT in HCC is 20 -70% [21]. In some cases, PVT can be the first echographic or radiologic sign of HCC in absence of any detectable focal lesion [20-22].
Although it seems reasonable to assume that a portal vein thrombus in a patient with HCC is malignant, and in a patient with no evidence of hepatic tumor is benign, in practice benign or malignant portal vein thrombi can oc- cur in either situation. This becomes more evident when a patient with a nodular HCC is treated with percuta- neous ablative techniques such as PEI or RFA. In such cases, the presence of a thrombus inside the PV branches located in the vicinity of the tumor could represent either a benign thrombosis as a consequence of the endothelial cell injury caused by the treatment, or an intravascular spread of a residual or a recurrent tumor [20].
The clinical value of recognizing malignant PVT in a patient with cirrhosis and HCC relies on the effect that malignant PVT has on the therapeutic strategy; patients with HCC (even uninodular and <5 cm) and malignant PVT are excluded from surgical treatment or imaging- guided PATs [23].
Real-time ultrasonography is a rapid and noninvasive method for evaluating the normal and the pathological portal venous system. The US signs of malignant PVT are the expansion of the caliber of vein, interruption of the PV wall and the presence of an arterial flow inside the PV thrombus at pulsed Doppler sonography.
The sensitivity of the pulsatile flow as a criteria for the diagnosis of malignant PVT vary between 62% and Fig 6. Inhomogeneous hepatic echostructure near a malignant
PVT: a) PVT biopsy; b) Histology aspect hematoxylin eosin stain 10x enlargement – well differentiated HCC; c) Paren- chymal biopsy; d) Histology of the parenchymal (hematoxylin eosin stain 40x enlargement) biopsy confirmed the well differ- entiated HCC
92% [17,20,24,25]. The sensitivity decreases even to 20% when small thrombi are analysed [4]. Beside size, failures of Doppler imaging to detect pulsatile flow in- side a thrombus are encountered in deep located or hy- povascular thrombi.
The presence of a pulsatile flow inside a PVT is fairly specific (86-100%) for malignant PVT [17,24,26]. How- ever, there are some cases in which, due to the presence of arterial portal venous shunting, a common phenom- enon in cirrhosis, pulsatile flow can be detected inside a benign thrombus, flow similar with that found in the non-thrombosed segment of the PV.
Using contrast-enhanced ultrasonography, the pulsa- tile flow as a diagnostic criteria of malignant thrombo- sis yielded a higher sensitivity and specificity (94% and 100% respectively) [27].
Of particular interest is the evaluation of a PVT that appears after a PAT such as PEI for HCC. The develop- ment of PVT after PATs may be related to the chemical or thermal injury of the PV with vasculitis and thrombus formation caused directly by PAT or to a venous inva- sion by a residual or recurrent tumor. The sensitivity and specificity of color Doppler sonography for the diagnosis of tumor thrombosis in such circumstances are 92% and 100%, respectively [20].
PVT as a sign of inaparent, occult HCC
In HCC, the US patterns generally result in focal echo- genic changes which are easily demonstrated, but also in normal features or, in a diffuse nonuniform structure that may be underrated and attributed to diffuse liver disease [22]. Caturelli et al [28] described 4 hepatic parenchy- mal echo patterns that can be found in liver cirrhosis: (a) normal homogeneous pattern; (b) bright liver pattern; (c) coarse pattern, and (d) coarse nodular pattern. The coarse pattern is represented by the presence of nonhomogene- ous, coarse, thick, uneven echo spots without any distinct hypoechoic nodules. The “coarse nodular pattern” has a background displaying the coarse echo pattern and multi- ple weak hypoechoic nodules (<6 mm in diameter). These 2 patterns were associated with a significantly increased risk for HCC in patients with HBV-, HCV and alcoholic cirrhosis. The “coarse and coarse nodular pattern” was found in the vicinity of PV in 10 of our patients with ma- ligant PVT. Core biopsy from these areas showed HCCs with the same pathological features in 6 of the 10 patients.
Contrast-enhanced helical computed tomography (CT) and contrast-enhanced magnetic resonance (MR) can suggest a malignant origin of the thrombus by visual- izing diffuse thrombus enhancement due to neovasculari- zation of the tumor infiltrating the vessel [29]. The sen- sitivity of CT in the characterisation of PVT in patients with HCC is only 68% [29].
Percutaneous biopsy of a portal vein thrombus can establish the nature of the thrombus, thus making the staging more accurate. It has been proved to be a feasible, accurate, safe and well-tolerated procedure.
Although the indications for PVTB in liver cirrhosis are not well established, in the following circumstances show in table II the PVT biopsy may be indicated [15,30].
The sensitivity of fine needle aspiration in the dif- ferential diagnosis of PVT ranges from 76 to 100%
[4,15,31]. Needle sampling error can result in both false- positive and false-negative diagnoses for malignant PV thrombi [15,30,31].
As a benign thrombus contains amorphous material, fibrin and blood [21,31] and not hepatocytes, sampling specimens from the periportal hepatic parenchima could lead to false-positive diagnoses. This could be prevent- ed by a continuous sonographic visualization while the needle is moved inside the thrombus and by choosing a proper needle tract inside the thrombus.
False-negative diagnoses could be produced if the portion of the malignant PVT, which is biopsied, does not contain malignant hepatocytes [15]. Performing the PVT biopsy closest to a hepatic tumor (if present) and choosing the longest possible segment of the PVT can prevent false-negative results.
Possible complications after PVT biopsy are: portal venous or hepatic arterial bleeding, laceration of a bile duct and formation of a vascular-biliary fistula, arteriov- enous fistula or pseudoanevrism. If we use color Doppler guidance in compliant patients with only intrahepatic PV thrombi and normal or corrected coagulations factors, the risk of PVT biopsy is comparable to that of the percuta- neous biopsy of HCCs [15,30-32].
The sensitivity of US guided PVT core biopsy found in our study was slightly higher than that found by Yang et al [33] (92.8% vs 87.5%). We obtained only 1 false negative result for malignant thrombi. This may be ex- plained by the sampling from an area which does not contain malignant hepatocytes [34]. In fact the CEUS studies of PVT have shown that frequently these thrombi have an inhomogenous enhancement in the arterial phase named “mosaic-picture”. It was postulated that in these cases a benign thrombosis was superimposed on the ini- tial neoplastic invasion of the portal vein [34].
Table II. Indications for portal vein thrombus biopsy 1. PVT with no imaging evidence of HCC 2. PVT remote from a histologically proven HCC 3. PVT adjacent to a nodule with an equivocal vascular pattern on imaging histology 4. PVT after a local treatment (PAT) of an HCC
In our patients’ group we had mostly patients with complete PVT , with distended and tumor filled PV . In such cases, if the needle path is safe, a core biopsy should be performed. For incomplete PVT with small thrombi, fine needle aspiration is the method of choice.
It has been shown recently that CEUS has a high sensitivity (88-97.7%), 100% specificity and very good accuracy (92.5-95.5%) in the characterisation of PVT [4,29,34]. The sensitivity of CEUS is higher than of con- trast enhanced CT (98 vs 67.6% ) , especially for non-oc- clusive thrombi (100% vs 57.1%) [29]. Taking the results of FNA, CEUS and follow up as “gold standard” it has been demonstrated that CEUS is superior even to FNA ( sensitivity 100% vs 89.6% ) in the diagnosis of PVT in patients with HCC [34]. When confirmation of malignant thrombosis is required, PVT biopsy can be guided on the result of CEUS in order to reduce false-negative results due to blind sampling [34].
CEUS guided percutaneous biopsy is a new tech- nique which has been shown to increase the sensitivity of percutaneous biopsy in tumoral diagnosis, especially in large tumors with frequent necrosis, complex cystic solid masses, less visible or poorly demarcated lesions [6-8,35]. Its superiority over the classic US guided bi- opsy has been demonstrated for liver [36,37], pulmonary [38], prostatic [39] and soft tissue tumors [40].
Our results showed that CEUS guided PVT biopsy in patient with liver cirrhosis and inapparent HCC is fea- sible, has a sensitivity of 100% and is safe. Guiding the needle inside the enhancing areas of the thrombus allows the sampling of tumoral cells and not nonmalignant tis- sue.
An interesting result of our study was to demonstrate that the “coarse and coarse nodular echo pattern” found in the vicinity of a malignant thrombus are frequently the expression of an inapparent HCC. The tumor could have been seen with CEUS which unfortunately was not avail- able in our Center at that time. Contrast enhanced CT performed in 5 of these patients failed to demonstrate the presence of an HCC.
Our study has some strengths and limitations. To our knowledge this is the first study where a very inhomog- enous hepatic ecotexture near a PVT was demonstrated to be caused by an HCC.
The low number of patients enrolled in the study rep- resents in fact the small number of patients with cirrhosis and malignant PVT with no evidence of an HCC lesion (inapparent or occult HCC) where pathological diagnosis was necessary in order to commence chemotherapy. Al- though some case reports have been published, this is the first prospective study to assess the role of core biopsy in malignant PVT and no evidence of an HCC. All other
published studies enrolled patients with detectable HCC where PVT biopsy was performed to stage the disease.
Most of the patients enrolled in the study had no CT studies. It is known that contrast enhanced CT is superior to conventional US in the detection of HCC so, probably some patients from our group would have had an intrahe- patic HCC that was missed by conventional US.
The most important result of this study was the excel- lent sensitivity and safety of the real time CEUS guided puncture of portal vein thrombosis. Although it com- prises a very small number of patients the results of this study recommend CEUS guided biopsy as an important diagnostic tool in the diagnosis of PVT.
In conclusion, a sonographically guided percutaneous portal vein thrombosis core biopsy is a safe, accurate and well tolerated procedure in the diagnosis of malignant portal vein thrombosis and no evidence of an HCC le- sion. The “coarse and coarse nodular echo pattern” found in the vicinity of a malignant thrombus are frequently the expression of an inapparent HCC. CEUS guided PVT bi- opsy is a new, promising method with excellent results in establishing the nature of a portal thrombus.
Conflict of interest: none Acknowledgement
The work is part of the research project within BI- OPTICON, number 2329/2008 PNCDI II 2007 – 2013.
References
1. Gaiani S, Bolondi L, Li Bassi S, Zironi G, Siringo S, Barbara L. Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. Gastroenterology 1991; 100: 160–165.
2. Valla DC, Condat B. Portal vein thrombosis in adults:
pathophysiology, pathogenesis and management. J Hepatol 2000; 32: 865–871.
3. Okuda K, Ohnishi K, Kimura K, et al. Incidence of portal vein thrombosis in liver cirrhosis. An angiographic study in 708 patients. Gastroenterology 1995; 89:279–286.
4. Tarantino L, Francica G, Sordelli I, et al. Diagnosis of benign and malignant portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma: color Doppler US, contrast-enhanced US, and fine-needle biopsy. Abdom Im- aging 2006; 31: 537-544.
5. Solbiati L, Tonolini M, Cova L, Goldberg SN. The role of contrast-enhanced ultrasound in the detection of focal liver leasions. Eur Radiol 2001; 11(Suppl 3): E15-E26.
6. Bang N, Bachmann Nielsen M, Vejborg I, Mellon Mogensen A. Clinical report: contrast enhancement of tu-
mor perfusion as a guidance for biopsy. Eur J Ultrasound 2000; 12: 159-161.
7. Skjoldbye B, Pedersen MH, Struckmann J, Burcharth F, Larsen T. Improved detection and biopsy of solid liver le- sions using pulse-inversion ultrasound scanning and con- trast agent infusion. Ultrasound Med Biol 2002; 28: 439- 444.
8. Meuwly JY, Schnyder P, Gudinchet F, Denys AL. Pulse- inversion harmonic imaging improves lesion conspicuity during US-guided biopsy. J Vasc Interv Radiol 2003; 14:
335-341.
9. Withers CE, Wilson SE. Portal vein thrombosis. In: Diag- nostic Ultrasound. Rumack CM, Wilson SR, Charboneau JW (eds). Mosby-Year Book, St.Louis, 1998; 118-119.
10. Parvey HR, Raval B, Sandler CM. Portal vein thrombosis:
imaging findings. AJR Am J Roentgenol 1994; 162 :77-81.
11. Weill FS. Cirrhosis and Portal Hypertension. In: Ultrasound Diagnosis of Digestive Disease. Weill FS (ed). Springer Verlag Berlin Heidelberg, 1996: 206.
12. Tessler FN, Gehring BJ, Gomes AS, et al. Diagnosis of por- tal vein thrombosis: value of color Doppler imaging. AJR Am J Roentgenol 1991; 157: 293-296.
13. Leen E, Becker D, Bolondi L. Prospective, open label mult- icentre study comparing the accuracy of unenhanced versus SonoVue enhanced ultrasonography in the characterization of focal liver lesion. Eur Radiol 2003;13:A270.
14. Rossi S, Rosa L, Ravetta V, et al. Contrast-enhanced versus conventional and color Doppler sonography for the detec- tion of thrombosis of the portal and hepatic venous systems.
AJR Am J Roentgenol 2006; 186:763-773.
15. Dodd GD 3rd, Carr BI. Percutaneous biopsy of portal vein thrombus: a new staging technique for hepatocellular carci- noma. AJR Am J Roentgenol 1993; 161: 229-233.
16. Terminology of nodular hepatocellular lesions. Internation- al Working Party. Hepatology 1995; 22: 983-993.
17. Dodd GD 3rd, Memel DS, Baron RL, Eichner L, Santiguida LA. Portal vein thrombosis in patients with cirrhosis:does sonographic detection of intrathrombus allow differentia- tion of benign and malignant thrombus? AJR Am J Roent- genol 1995; 165: 573-577.
18. Amitrano L, Brancaccio V, Guardascione MA, et al. Portal vein thrombosis after variceal endoscopic sclerotherapy in cirrhotic patients: role of genetic thrombophilia. Endoscopy 2002; 34: 535–538.
19. Politoske D, Ralls P, Korula J. Portal vein thrombosis fol- lowing endoscopic variceal sclerotherapy. Prospective con- trolled comparison in patients with cirrhosis. Dig Dis Sci 1996; 41: 185–190.
20. Lencioni R, Caramella D, Sanguinetti F, Battolla L, Falaschi F, Bartolozzi C. Portal vein thrombosis after per- cutaneous ethanol injection for hepatocellular carcinoma:
value of color Doppler sonography in distinguishing chemi- cal and tumor thrombi. AJR Am J Roentgenol 1995; 164:
1125–1130.
21. Cedrone A, Rapaccini GL, Pompili M, et al. Portal vein thrombosis complicating hepatocellular carcinoma. Value of ultrasound-guided fine-needle biopsy of the thrombus in
the therapeutic mangement. Liver 1996; 16: 94-98.
22. Joly JP, Delamarre J, Razafimahaleo A, Sevestre H, Tossou H, Capron JP. Occult hepatocellular carcinoma in cirrhosis:
value of ultrasound-guided biopsy of portal vein system thrombus. Abdom Imaging 1993; 18: 344-346.
23. Minagawa M, Makuuchi M, Takayama T, Ohtomo K. Se- lection criteria for hepatectomy in patients with hepatocel- lular carcinoma and portal vein tumor thrombus. Ann Surg 2001; 233: 379–384.
24. Tanaka K, Numata K, Okazaki H, Nakamura S, Inoue S, Takamura Y. Diagnosis of portal vein thrombosis in patients with hepatocellular carcinoma: efficacy of color Doppler sonography compared with angiography. AJR Am J Roent- genol 1993; 160: 1279-1283.
25. Pozniak MA, Baus KM. Hepatofugal arterial signal in the main portal vein: an indicator of intravascular tumor spread. Radiology 1991; 180: 663-666.
26. Furuse J, Matsutani S, Yoshikawa M, et al. Diagnosis of portal vein tumor thrombus by pulsed Doppler ultrasonog- raphy. J Clin Ultrasound 1992; 20: 439–446.
27. Ricci P, Cantisani V, Biancari F, et al. Contrast-enhanced color Doppler US in malignant portal vein thrombosis. Acta Radiol 2000; 41: 470-473.
28. Caturelli E, Castellano L, Fusilli S, et al. Coarse nodular US pattern in hepatic cirrhosis: risk for hepatocellular car- cinoma. Radiology 2003; 226: 691-697.
29. Rossi S, Ghittoni G, Ravetta V, et al. Contrast-enhanced ultrasonography and spiral computed tomography in the detection and characterization of portal vein thrombosis complicating hepato-cellular carcinoma. Eur Radiol 2008;
18: 1749-1756.
30. Sparchez Z. Color-Doppler and percutaneous thrombus bi- opsy in the differential diagnosis of portal vein thrombo- sis in liver cirrhosis. Rom J Gastroenterol 2001; 10: 37-42.
31. Vilana R, Bru C, Bruix J, Castells A, Sole M, Rodes J. Fine- needle aspiration biopsy of portal vein thrombus: value in detecting malignant thrombosis. AJR Am J roentgenol 1993; 160: 1285-1287.
32. Ch Yu S, Metreweli C, Lau WY, Leung WT, Liew CT, Le- ung NW. Safety of percutaneous biopsy of hepatocellular carcinoma with an 18 gauge automated needle. Clin Radiol 1997;52 : 907-911.
33. Yang L, Lin LW, Lin XY, et al. Ultrasound-guided fine nee- dle aspiration biopsy in differential diagnosis of portal vein tumor thrombosis. Hepatobiliary Pancreat Dis Int 2005; 4:
234-238.
34. Sorrentino P, D’Angelo S, Tarantino L, Ferbo U, Bracigliano A, Vecchione R. Contrast-enhanced sonography versus bi- opsy for the differential diagnosis of thrombosis in hepa- tocellular carcinoma patients. World J Gastroenterol 2009;
15: 2245-2251.
35. Spârchez Z, Radu P, Zaharia T, Kacso G, Grigorescu I, Badea R. Contrast enhanced ultrasound guidance. A new tool to improve accuracy in percutaneous biopsies. Medical Ultrason 2010; 12: 133-138.
36. Wu W, Chen MH, Yin SS, et al. The role of contrast-en- hanced sonography of focal liver lesions before percutane-
ous biopsy. AJR Am J Roentgenol 2006; 187: 752-761.
37. Sparchez Z, Radu P, Zaharia T, Grigorescu I, Badea R.
Kacso G, Botis G. Role of contrast enhanced ultrasound (CEUS) in percutaneous biopsy of liver tumors. J Hepatol 2010; 52(Suppl 1): S234.
38. Sartori S, Nielsen I, Trevisani L, Tombesi P, Ceccotti P, Abbasciano V. Contrast-enhanced sonography as guidance for transthoracic biopsy of a peripheral lung lesion with large necrotic areas. J Ultrasound Med 2004; 23: 133-136.
39. Mitterberger M, Horninger W, Pelzer A, et al. A prospec- tive randomized trial comparing contrast-enhanced target- ed versus systematic ultrasound guided biopsies: impact on prostate cancer detection. Prostate 2007; 67: 1537- 1542.
40. De Marchi A, Brach del Prever EM, Linari A, et al. Ac- curacy of core-needle biopsy after contrast-enhanced ultra- sound in soft-tissue tumours. Eur Radiol 2010; 20: 2740- 2748.
