P. Pini

The impact of vascular and nonvascular findings on the noninvasive diagnosis of small hepatocellular carcinoma based on the EASL and AASLD criteria.

OBJECTIVES:Noninvasive criteria for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis, recommended by the European Association for the Study of Liver (EASL) in 2001 and by the American Association for the Study of Liver Diseases (AASLD) in 2005, have left a number of small liver neoplastic nodules undefined. We designed this prospective study in 2003 with the aims of assessing the diagnostic contribution of vascular contrast-enhanced techniques and investigating the possible additional contribution of superparamagnetic iron oxide magnetic resonance (SPIO-MR) in this setting.METHODS:Between 2003 and 2005, 75 consecutive small (10–30 mm) liver nodules detected at ultrasonography in 60 patients with cirrhosis were prospectively submitted to contrast-enhanced ultrasound (CEUS), helical-computed tomography (helical-CT), and gadolinium magnetic resonance (gad-MR), each blinded to the other. A total of 68 nodules were also studied with SPIO-MR at the same time as gad-MR.RESULTS:Using the EASL noninvasive criteria, the diagnosis of HCC was established in 44 of 55 (80%) nodules with a final diagnosis of HCC. Gad-MR was the most sensitive technique for detecting the typical vascular pattern. SPIO-MR showed a pattern consistent with HCC in 5 of 10 HCCs, not satisfying the EASL noninvasive criteria, and was negative in 17 of 18 (94.4%) nonmalignant nodules. The review of the present case series according to the AASLD criteria for the noninvasive diagnosis of HCC yielded a sensitivity rate of 81.8%.DISCUSSION:This study shows that both EASL and AASLD noninvasive recall strategies for nodules of 10–30 mm in the cirrhotic liver, based on the vascular pattern of nodules, have a false-negative rate of ∼20%. SPIO-MR may increase the diagnostic potential of noninvasive techniques, contributing to the diagnosis of HCC lacking a typical vascular pattern.

Real time contrast enhanced ultrasonography in detection of liver metastases from gastrointestinal cancer

BackgroundContrast enhanced ultrasound (CEUS) is an imaging technique which appeared on the market around the year 2000 and proposed for the detection of liver metastases in gastrointestinal cancer patients, a setting in which accurate staging plays a significant role in the choice of treatment.MethodsA total of 109 patients with colorectal (n = 92) or gastric cancer prospectively underwent computed tomography (CT) scan and conventional US evaluation followed by real time CEUS. A diagnosis of metastases was made by CT or, for lesions not visibile at CT, the diagnosis was achieved by histopathology or by a malignant behavior during follow-up.ResultsOf 109 patients, 65 were found to have metastases at presentation. CEUS improved sensitivity in metastatic livers from 76.9% of patients (US) to 95.4% (p <0.01), while CT scan reached 90.8% (p = n.s. vs CEUS, p < 0.01 vs US). CEUS and CT were more sensitive than US also for detection of single lesions (87 with US, 122 with CEUS, 113 with CT). In 15 patients (13.8%), CEUS revealed more metastases than CT, while CT revealed more metastases than CEUS in 9 patients (8.2%) (p = n.s.).ConclusionCEUS is more sensitive than conventional US in the detection of liver metastases and could be usefully employed in the staging of patients with gastrointestinal cancer. Findings at CEUS and CT appear to be complementary in achieving maximum sensitivity.

Influence of the Spleen on Portal Haemodynamics: a Non-invasive Study with Doppler Ultrasound in Chronic Liver Disease and Haematological Disorders

Background: Splanchnic haemodynamic parameters for the differential diagnosis of splenomegalies of different origins are still suboptimal and the role of spleen enlargement in cirrhosis remains controversial. In an attempt to elucidate these questions, we assessed splanchnic haemodynamics in chronic liver diseases and various other disorders with splenomegaly. Methods: Study groups comprised: (i) patients with chronic liver disease (89 with cirrhosis, 35 with chronic hepatitis), (ii) patients with splenomegaly without relevant portal hypertension (14 with haematological splenomegaly and 25 liver transplant recipients without complications), (iii) 15 patients with arterial hypertension, (iv) 22 healthy controls. In all subjects, spleen size, portal flow parameters and splenic artery resistance index were measured using duplex-Doppler ultrasound. Results: Splenic artery resistance index was significantly and selectively increased in patients with cirrhosis (0.63, whereas all other group means ranged between 0.53 and 0.56; P < 0.01). Portal flow velocity was significantly decreased in cirrhosis ( P < 0.01). The combination of these two parameters provided an accuracy of 87.5% in distinguishing portal hypertensive from haematological splenomegaly. In patients with cirrhosis, the degree of spleen enlargement was positively correlated with increasing portal flow volume, portal vein diameter and variceal size, whereas splenic resistance index and portal velocity did not differ in connection with spleen size. Conclusions: Splenoportal Doppler sonography provides specific findings in cirrhosis and may therefore be a useful tool in differentiating between splenomegaly of portal hypertensive or haematological origin. In patients with cirrhosis, the presence of splenomegaly is associated with the presence of larger oesophageal varices.

Treatment of hepatocellular carcinoma in Child-Pugh B patients.

BACKGROUND The frequency with which patients in Child-Pugh B having hepatocellular carcinoma are treated following the international guidelines according to the Barcelona Clinic Liver Cancer stages is unknown. AIMS To investigate treatment allocation for Child-Pugh B patients in different tumour stages, with particular interest in the intermediate stage. METHODS Patients were retrospectively identified from a consecutively collected series. Treatment was carried out primarily according to the guidelines. RESULTS Of 86 Child-Pugh B patients, 45 were Barcelona early stage, of which the Child-Pugh scores were 46.7% B7, 33.3% B8, 20.0% B9; 27 patients were intermediate stage (B7 59.3%, B8 37.0% and B9 3.7% respectively), 12 were advanced (41.7% B7, 25.0% B8 and 33.3% B9) and 2 were terminal (both B9). In the intermediate stage, transarterial chemoembolization (or ablation) was performed in 68.8% of the Child-Pugh B7 patients, 50% of the B8 patients and 0% of the B9 patients. Median survival of the intermediate patients was 8.0 months (9.0 in B7 vs. 6.0 in -B8/B9, P=0.048). Survival of the intermediate stage patients undergoing chemoembolisation was 22.0 months in Child-Pugh B7 and 6.0 in B8. CONCLUSIONS Approximately half of the intermediate stage patients can undergo locoregional treatment with good survival when in the Child-Pugh B7. The Child-Pugh numeric score impacts survival, suggesting that this tumour stage be refined.

Liver AL amyloidosis as a possible cause of high liver stiffness values.

The liver is a common site of amyloid deposition in primary systemic amyloidosis. We report the case of a 52-year-old white woman complaining of hepatomegaly, high levels of alkaline phosphatase and serum gamma-glutamyl transferase. Other laboratory tests showed proteinuria with light-chain type lambda. Color Doppler ultrasonography showed an enlarged bright liver with hepatopetal portal blood flow. Fine-needle aspiration biopsy of abdominal fat, with Congo red stain, was positive for amyloid. No liver biopsy was performed, but transient elastography showed high liver stiffness values (75 kPa), suggestive of amyloid infiltration, as other causes of elevation had been ruled out by clinical, laboratory and radiological findings. Bone marrow morphology and immunoistochemistry confirmed low-grade plasmacytoma with amyloidosis.

Acute systemic, splanchnic and renal haemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end‐stage cirrhosis

To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end‐stage cirrhosis.

Efficacy of radioembolization according to tumor morphology and portal vein thrombosis in intermediate–advanced hepatocellular carcinoma

PURPOSE We analyzed overall survival (OS) following radioembolization according to macroscopic growth pattern (nodular vs infiltrative) and vascular invasion in intermediate-advanced hepatocellular carcinoma (HCC). METHODS Between September 2005 and November 2013, 104 patients (50.0% portal vein thrombosis [PVT], 29.8% infiltrative morphology) were treated. RESULTS Median OS differed significantly between patients with segmental and lobar or main PVT (p = 0.031), but was 17 months in both those with patent vessels and segmental PVT. Median OS did not differ for infiltrative and nodular HCC. Median OS was prolonged in patients with a treatment response at 3 months (p = 0.023). Prior TACE was also a significant predictor of improved OS. CONCLUSION A further indication for radioembolization might be infiltrative HCC, since OS was similar to nodular types.

A phase I study of continuous hepatic arterial infusion of Irinotecan in patients with locally advanced hepatocellular carcinoma

PURPOSE Aim of this phase I study was to identify the maximum tolerated dose and dose limiting toxicity of continuous infusion of Irinotecan through a port-a-cath placed in the hepatic artery in patients with hepatocellular carcinoma and cirrhosis to explore new strategies in advanced hepatocellular carcinoma. Response rate and time-to-progression were analysed. METHODS Irinotecan was delivered as a five-day continuous infusion every 21 days, with increases of 2.5mg/m(2)/day every three patients, starting from 7.5mg/m(2)/day. Dose limiting toxicity corresponded to one patient in each triplet developing G4 haematological or G3 non-haematological toxicity, confirmed in two triplets. Twenty-eight patients (17 Child-Pugh A, 11 B) received treatment and tumour response was assessed after three courses completed by 22 patients. RESULTS Dose limiting toxicity was G3 diarrhoea in two patients, reached at 27.5mg/m(2)/day and the recommended dose was set at 25mg/m(2)/day. Nineteen of 30 patients experienced adverse events related to porth-a-cath placement and one died from liver ischemia and sepsis. Median time-to-progression was 11.3 months. CONCLUSION Intrarterial infusion of Irinotecan is feasible in patients with hepatocellular carcinoma on cirrhosis at a recommended dose of 25mg/m(2)/day, with no major adverse drug-related events, but with some concerns about the insertion and management of the intra-arterial device.

A new horizon in the prevention of the postembolization syndrome after transcatheter arterial chemoembolization for hepatocellular carcinoma

Endovascular embolizing treatments, represented mainly by transcatheter arterial chemoembolization (TACE), are widely used in the treatment of hepatocellular carcinoma (HCC). Almost half of patients undergo TACE at some point in their course of disease, making it the most commonly used therapy in HCC. Lencioni et al. conducted a systematic review evaluating the safety of lipiodol-TACE (or conventional TACE). A total of 21,461 adverse events occurred in 15,351 patients who underwent at least 27,497 treatment sessions in the included 217 articles. Among them, almost half (47.7%) were related to postembolization syndrome (PES), a condition that includes noninfectious fever, nausea/vomiting, malaise and asthenia, pain, and enzyme elevation. PES is also observed after either TACE with drug-eluting beads, with rates of 25%-42% for grade 2 PES, or after radioembolization with Yttrium90, with a metanalysis showing an overall occurrence rate of 18%20%, regardless of whether glass or resin embolizing beads were used. Symptoms of PES (nausea, fever, and malaise/asthenia) are not specific to TACE, but rather represent a generalized event reported to occur after embolization of other abdominal organs, such as the spleen, kidney, uterus, which only differ in terms of location of the pain. PES is, in fact, reported to be caused by the release of inflammatory cytokines in the bloodstream. Strategies to reduce its occurrence are warranted, but no method has yet been established, and most occasional reports dealt more with the treatment after its occurrence, rather than systematic prevention. A small randomized trial testing the addition of local anesthetics to the embolizing mixture showed only the reduction of painkiller drugs in the next few days, but not a reduction in the occurrence of PES. Prophylactic use of nonsteroidal antinflammatory drugs has been adopted in some centers to prevent PES after uterine embolization, but clearly these drugs are contraindicated in patients who have cirrhosis and HCC. It seems, therefore, that PES is an unavoidable consequence of TACE that is to be tolerated for the major benefit of prolonged survival. However, PES is not only an inconvenience for patients— which occasionally discourages subsequent TACE courses due to the threat of recurrence—but it often prolongs hospital stays, causes diagnostic dilemmas in case of fever and pain leading to additional diagnostic testing, and is therefore a burden for physicians and administrators. Moreover, in a recent study, the occurrence of PES was associated with worse survival after TACE. Because this study was retrospective and was not designed with adequate stratification, the Abbreviations: HCC, hepatocellular carcinoma; PES, postembolization syndrome; TACE, transcatheter arterial chemoembolization.

1015 THE CHALLENGE OF TREATING HCC IN CHILD-PUGH B: NEED FOR SUBCLASSIFICATION

Background and Aims: Treatment of HCC in cirrhosis should provide effective antitumoral treatment and concurrently preserve liver function. According to EASL and AASLD guidelines HCCCPTB patients should be submitted to treatment following tumor extent categorized with Barcelona classification. However, the decision has to be individualized in order to avoid overtreatment and precipitating liver failure. Aim of the present study was to investigate treatment allocation in Child–Pugh B HCC patients subgrouped according to BCLC and Child–Pugh, to determine whether within the B class significant differences exist in eligibility to treatments. Methods: Among all consecutive patients with first diagnosis of HCC referred to our Centre between March 2001 and December 2007, we retrospectively identified and evaluated for treatment Child–Pugh B patients. Treatment was decided following individual assessment of tumor burden, BCLC stage, liver function, technical requirements, potential risks for tumor treatment and expected impact on liver function. Results: A total of 86 patients were observed: 42 were scored as Child–Pugh B7, 28 as B8 and 16 as B9. Staging was BCLC-A4 in 45 patients (47%, 33% and 20% in B7, B8 and B9 respectively), BCLC-B in 27 (59%, 37% and 4% respectively), BCLC-C in 12 (42%, 25% and 33% respectively) and BCLC-D in 2 (100% Child–Pugh B8). Patients with early HCC (BCLC-A4) could almost always be offered curative treatments if B7 (95%) and often if B8 (73%) or B9 (78%), with very few patients (respectively 0%, 7% and 11%) allocated to only best supportive care (BSC). The rate of patients who were not offered effective treatments was significantly higher in intermediate patients with increasing Child–Pugh score (BCLC-B) with 37.5% in B7, 50% in B8, 1 of 1=100% in B9. Similarly the rate of advanced patients (12 BCLC-C/D) who were allocated to BSC was 20% in B7, 67% in B8 and 83% in B9. Discussion: The Child–Pugh B class is very heterogeneous and significant differences were found in the possibility to allocate patients to different treatments according to the progression of hepatic dysfunction from CPT-B7 to B9. A subclassification of patients in Child–Pugh B appears warranted to the aim of their treatment allocation.