Short- and long-term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) affects hepatic perfusion, and might have an impact on portal pressure in patients with hepatocellular carcinoma (HCC). Objective: The objective of this article is to report the secondary outcome "hepatic hemodynamics" from the AVATACE trial, a prospective randomized, placebo-controlled trial on the efficacy of conventional TACE in combination with bevacizumab or placebo. Methods: Hepatic venous pressure gradient (HVPG) was measured at baseline (prior to first TACE), within nine days ("acute effects"), two months ("intermediate effects") and six months ("long-term effects") after the first TACE. Results: Of 28 patients with early-intermediate stage HCC, n = 20 (71%) had clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) at baseline (median, 12 (interquartile range (IQR): 9-19) mmHg). TACE had neither "acute effects" nor "intermediate effects" on HVPG. However, in 13 patients with available HVPG measurement at month 6, there was a significant increase in HVPG (median, 16 (IQR: 11-19) mmHg) compared with baseline (median, 10 (IQR: 5-12) mmHg; p = 0.007). Portal hypertension-related complications occurred exclusively in patients with CSPH (8 (40%) vs 0). Conclusions: Repeated TACE was associated with a significant long-term increase in HVPG. This should be considered when deciding whether to continue with TACE or switch to systemic treatment, since CSPH drives the development of complications.

Austrian consensus guidelines on imaging requirements prior to hepatic surgery and during follow-up in patients with malignant hepatic lesions.

Rapid advances in imaging technology have improved the detection, characterization and staging of colorectal liver metastases, hepatocellular carcinoma and cholangiocarcinoma. A variety of imaging modalities are available and play a pivotal role in the work-up of patients, particularly as imaging findings determine resectability. Surgery often represents the only measure that can render long-term survival possible. Imaging is also indispensable for the assessment of responses to neoadjuvant treatment and for the detection of recurrence. At a consensus meeting held in June 2017 in Vienna, Austria, Austrian experts in the fields of surgery and radiology discussed imaging requirements prior to and after hepatic surgery for malignant liver lesions. This consensus was refined by online voting on a total of 47 items. Generally, the degree of consensus was high. The recommendations relate to the type of preferred preoperative imaging modalities, technical settings with respect to computed tomography and magnetic resonance imaging, use of contrast agents, reporting, postoperative follow-up, and long-term follow-up. Taking local resources into account, these consensus recommendations can be implemented in daily clinical practice at specialized centers as well as outpatient diagnostic institutes in Austria.

Early response evaluation using CT-perfusion one day after transarterial chemoembolization for HCC predicts treatment response and long-term disease control.

PURPOSE: To determine the value of CT perfusion (CTP) for early response assessment after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between April 2013 and April 2015, 41 HCC (16 patients) were included in this study. CT perfusion was performed before and one day after TACE. Blood flow (BF), blood volume (BV), time to start (TTS), arterial liver perfusion (ALP), portal liver perfusion (PVP) and hepatic perfusion index (HPI) were measured. Quantitative perfusion values before and after TACE were compared to the response assessed using mRECIST criteria six weeks after TACE and long-term outcome was assessed. RESULTS: Twenty-one lesions (51%) had complete remission (CR) and five (12%) had partial response (PR) six weeks after TACE. CTP parameters were significantly reduced after TACE in responders (PR, CR, p<0.001) while no difference was observed in non-responders. ALPpost was superior in the prediction of CR compared to BFpost and BVpost (p<0.001) with a sensitivity, specificity, PPV, NPV, and accuracy of 90%, 90%, 91%, 90%, and 91%, respectively. Only 3/21 lesions with CR recurred, with a mean local-recurrence-free survival of 19.6 months. CONCLUSION: CT perfusion detects lesions with complete response one day after TACE, and is a feasible tool for early response assessment.

Hepatocellular Carcinoma: A Phase II Randomized Controlled Double-Blind Trial of Transarterial Chemoembolization in Combination with Biweekly Intravenous Administration of Bevacizumab or a Placebo.

PURPOSE: To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double-blind phase II trial. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early- or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P < .05 indicated a significant difference. RESULTS: Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years ± 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients received bevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. CONCLUSION: No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE.

Non-invasive diagnosis of focal liver lesions: an individualized approach.

Modern cross-sectional imaging with multidetector computed tomography (MDCT) or magnetic resonance imaging (MRI) often reveals small focal liver lesions, which puts pressure on the reporting radiologist to characterize these tiny lesions. On the other hand, in patients with underlying diffuse liver disease, such as cirrhosis or severe steatosis, the detection of focal liver lesions can be quite difficult. Strategies for optimal detection and characterization of focal liver lesions should be developed according to the clinical situation, the likelihood of malignant disease and the presence of underlying diffuse liver disease. The presence or absence of a clinical history of cancer determines the algorithm for further characterization: work-up with contrast-enhanced MRI, biopsy or follow-up. In patients with chronic liver disease, recent guidelines on the detection of hepatocellular carcinoma (HCC) favour the use of multiphasic MRI or MDCT, which allows confident diagnoses of HCC >1 cm. For lesions <1 cm in chronic liver disease, follow-up is recommended. In patients with moderate to severe steatosis, contrast-enhanced MDCT has low diagnostic yield for the detection of liver lesions; contrast-enhanced MRI is far superior. This review describes successful strategies for the detection and characterization of focal liver lesions in different clinical scenarios.

Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib.

PURPOSE: To compare the efficacies of transarterial chemoembolization (TACE) and sorafenib in patients with advanced-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The retrospective analysis of the data was approved by the institutional review board; the requirement to obtain informed consent was waived. Three hundred seventy-two patients with HCC were treated between January 1999 and December 2009. Patients with advanced HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging classification (Child-Pugh class A or B, Eastern Cooperative Oncology Group performance status of 1-2, and/or macrovascular invasion or extrahepatic metastasis) were included in the study (n = 97). Thirty-four patients underwent conventional TACE with doxorubicin plus lipiodol or TACE with drug-eluting beads; 63 patients were treated with sorafenib. RESULTS: The median duration of sorafenib treatment was 4.6 months (95% confidence interval [CI]: 3.2, 6.0 months). The median number of TACE sessions per patient was 3 ± 2. Side effects of TACE and sorafenib were comparable to those reported in the literature. The median time to progression was similar between the two treatment groups (P = .737). The median overall survival was 9.2 months (95% CI: 6.1, 12.3 months) for patients treated with TACE and 7.4 months (95% CI: 5.6, 9.2 months) for those treated with sorafenib (P = .377). Only Child-Pugh class was associated with a better overall survival at uni- and multivariate analysis. CONCLUSION: TACE achieved a promising outcome in select patients with advanced HCC (BCLC stage C).

Austrian Joint ÖGGH-ÖGIR-ÖGHO-ASSO position statement on the use of transarterial chemoembolization (TACE) in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is one of the most frequently applied standard treatments for this disease. The role for TACE is fairly well defined within the most widely used treatment algorithm for HCC, die Barcelona Clinic Liver Cancer (BCLC) staging system and treatment algorithm. But no general treatment algorithm will go into the technical details of any procedure and several patients will not fit ideally into the patient groups predefined in BCLC or any other treatment algorithm. Furthermore, indications and contraindications sometimes are viewed differently by the various medical specialties involved in taking care of such patients. We present here the joint expert position statement of the Austrian Societies of Gastroenterology and Hepatology (ÖGGH), Interventional Radiology (ÖGIR), Hematology and Oncology (ÖGHO), and Surgical Oncology (ASSO) on the technical aspects, indications, and contraindication for the use of TACE in the management of HCC.

Pancreatic adenocarcinoma.

Adenocarcinoma is the most common malignant pancreatic tumor, affecting the head of the pancreas in 60-70% of cases. By the time of diagnosis, at least 80% of tumors are unresectable. Helical computed tomography (CT) is very effective in detecting and staging adenocarcinoma, with a sensitivity of up to 90% for detection and an accuracy of 80-90% for staging, but it has limitations in detecting small cancers. Moreover, it is not very accurate for determining nonresectability because small liver metastases, peritoneal carcinomatosis, and subtle signs of vascular infiltration may be missed. Multidetector-row CT (MDCT) has brought substantial improvements with its inherent ability to visualize vascular involvement in three dimensions. MDCT has been found to be at least equivalent to contrast-enhanced magnetic resonance imaging (MRI) for detecting adenocarcinoma. MRI can be used as a problem-solving tool in equivocal CT: MRI may help rule out pitfalls, such as inflammatory pseudotumor, focal lipomatosis, abscess, or cystic tumors. Mangafodipir-enhanced MRI reveals a very high tumor-pancreas contrast, which helps in diagnosing small cancers. Endosonography is, if available, also a very accurate tool for detecting small cancers, with a sensitivity of up to 98%. It is the technique of choice for image-guided biopsy if a histologic diagnosis is required for further therapy.