The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD. Material and methods: Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated. Results: AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination. Conclusions: We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.

Selective internal radiation therapy of hepatic tumours: is coiling of the gastroduodenal artery always beneficial?

AIM: To assess the effect of gastroduodenal artery (GDA) occlusion prior to selective internal radiation therapy (SIRT) with regards to arterial hepato-intestinal collateralization (HIC). MATERIALS AND METHODS: Six hundred and six patients were scheduled for SIRT between 2006 and 2012 at University Hospital Essen, Germany. Digital subtraction angiography (DSA) followed by administration of 99m-technetium labelled human serum albumin microspheres ((99m)Tc-HSAM) and single-photon emission computed tomography combined with computed tomography (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic tumour load, GDA coil embolization was considered. In subsequent (99m)Tc-HSAM rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed. RESULTS: The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86 patients did not undergo SIRT due to the patients' clinical status or SIRT contraindications. In 28 of the remaining 64 patients, newly apparent or reopened HIC were seen either at the site of the proximal GDA (n = 21) or in the periphery of the hepatic arteries (n = 7). In 25 of these 28 patients, the HIC could be occluded or the catheter position could be changed achieving a safe (90)Y application. However, due to the newly visible HIC in three of 28 patients, SIRT was regarded as unsafe and was abandoned. CONCLUSION: Coil embolization of the GDA may induce arterial hepato-intestinal collaterals. Although most of these collaterals do not impede (90)Y administration, SIRT may become unfeasible in specific occasions. Hence, segmental or lobar SIRT instead of a whole-liver approach with coiling of the GDA is recommended.

Hepatic volume changes after lobar selective internal radiation therapy (SIRT) of hepatocellular carcinoma.

AIM: To assess volume changes of treated and non-treated liver segments after selective internal radiation therapy (SIRT) in patients with hepatocellular carcinoma (HCC) and compromised hepatic function due to cirrhosis over a time course of 12 months after SIRT. MATERIALS AND METHODS: All patients underwent SIRT of the right liver lobe with yttrium 90 (Y-90). Absolute volumes of the right liver lobe (RLV) and left liver lobe (LLV) were assessed using computed tomography (CT) before and 1, 3, 6, 9, and 12 months after SIRT. Changes at follow-up relative to baseline volumes were analysed ("normalized" volumes). Furthermore, the relative volume of the LLV [LLV/(RLV + LLV)] was calculated ("relative" volumes). For statistical analysis p < 0.05 was considered statistically significant. RESULTS: Forty-five HCC patients (36 men, nine women, mean age 71.9 years, range 55-90 years) were studied. The mean baseline RLV and LLV reached 1116 ml [95% confidence intervals (CI): 1006-1226 ml] and 601 ml (95% CI: 514-688 ml), respectively. At 6 months following radioembolization, the LLV increased by 30.8% (RLV -33.9%), with the relative LLV increasing from 35% (pre-radioembolization) to 50.5%. RLV further decreased and LLV increased 12 months after SIRT (nRLV -44.9%, nLLV +40.1%, relative LLV 56.5%). All changes were significant. CONCLUSION: Constraints of liver function after radioembolization of one liver lobe can be partially compensated through hypertrophy of the contralateral lobe. The rate of volumetric changes is the highest in the first 6 months following radioembolization. The present data can also be the basis to propagate radiation lobectomy for selected patients, simultaneously providing tumour control and future remnant liver hypertrophy before curative hemihepatectomy.

Radioembolization of hepatic tumors: flow redistribution after the occlusion of intrahepatic arteries.

PURPOSE: Radioembolization using 90yttrium is an emerging therapy option for unresectable liver malignancies. In order to reduce the number of yttrium injections, endovascular occlusion of a segmental hepatic artery has been proposed. The aim of this study was to assess whether sufficient vascular redistribution of the occluded liver segments through intrahepatic collaterals can be observed. MATERIALS AND METHODS: 27 patients with hepatocellular carcinoma (n = 16) or hepatic metastases (n = 11) were studied. Hepatic angiography was performed on average 16 days prior to radioembolization. The segment II/III artery (n = 9) or the segment IV artery (n = 18) was occluded using coils. Technectium-99m-labeled macroaggregated albumin (99mTc-MAA) was injected into the right and the remaining part of the left hepatic artery in order to identify any hepatic volume not included in the perfused area. Patients underwent a SPECT/CT on average 1 h after the 99mTc-MAA injection. Two radiologists evaluated the SPECT/CT scans regarding the presence of non-perfused hepatic segments. Furthermore, hepatic perfusion was assessed by digital subtraction angiography (DSA) on the day of radioembolization. RESULTS: In 16/27 patients (59%) a perfusion of the occluded liver segment was visible on the SPECT/CT scan. In 8/11 patients without flow redistribution at the time of the SPECT/CT, perfusion of the occluded segment through hepatic collaterals was observed during angiography prior to radioembolization. Hence, flow redistribution was eventually found in 24/27 patients (89%). CONCLUSION: Flow redistribution after the occlusion of intrahepatic arteries prior to radioembolization can be successfully induced in the majority of patients with anatomical variants of the hepatic arteries.

[Selective internal radiotherapy (SIRT) for hepatocellular carcinoma]. / Selektive interne Radiotherapie (SIRT) beim hepatozellulären Karzinom.

Microsphere-based radioembolization represents a new generation of therapeutics in interventional oncology. The intrahepatic application of radioactive microspheres via the hepatic artery allows locoregional therapy of diffuse or multifocal liver tumors, for which to date systemic therapy was the only remaining option. The current standard for this selective internal radiotherapy or radioembolization is yttrium-90 glass or resin microspheres. This review discusses the indications, the technique, and the therapeutic results of microsphere-based radioembolization.

Angiography-based C-arm CT for the assessment of extrahepatic shunting before radioembolization.

PURPOSE: To retrospectively assess the accuracy of angiography-based C-arm CT for the detection of extrahepatic shunting before SIRT. MATERIALS AND METHODS: 30 patients (mean age: 64+/-12 years) with hypervascularized hepatic tumors underwent hepatic angiography, coil embolization of gastrointestinal collaterals and 99mTc-macroaggregated albumin (MAA) SPECT/CT before SIRT. Before MAA injection via a microcatheter from the intended treatment position, an angiography and angiography-based C-arm CT (XperCT, Philips Healthcare) were acquired. Angiographies and XperCT were performed from 48 microcatheter positions followed by MAA injections and MAA-SPECT/CT. MAA-SPECT/CT served as the reference standard for determining the accuracy of hepatic arteriography and C-arm CT for the detection of extrahepatic shunting. RESULTS: MAA-SPECT/CT revealed extrahepatic shunting in 5 patients (17%). Hepatic arteriography yielded a true negative in 22 (73%), a false negative in 5 (17%), and an unclear result in 3 patients (10%). C-arm CT yielded a true positive in 3 (10%), true negative in 24 (80%), false positive in 1 (3%), and false negative in 2 patients (7%). The specificity and the NPV of hepatic arteriography for the detection of extrahepatic shunting were 88% and 81%, respectively. For C-arm CT the sensitivity, specificity, PPV, NPV, and accuracy for the detection of extrahepatic shunting were 60%, 96%, 75%, 92%, and 90%, respectively. CONCLUSION: C-arm CT offers additional information to angiography when assessing SIRT patients for extrahepatic shunting. More accurate detection of extrahepatic shunting may optimize the workflow in SIRT preparations by avoiding unnecessary repeat angiographies.

B-cell lymphoma in a patient with WHIM syndrome.

WHIM syndrome is a rare congenital familial syndrome consisting of warts, hypogammaglobulinemia, infections, and myelokathexis. We describe a 30-year-old man with WHIM syndrome, in whom red dermal facial nodules developed. The diagnosis of B-cell lymphoma was established with biopsy and immunohistochemical studies. To our knowledge, this is the first reported case of WHIM syndrome complicated by a B-cell lymphoma.

The real F.M. Urban.

F.M. Urban made important contributions in psychometry and is best known for his introduction of a correction in the "Müller-Urban weights." Born in Austria, he came to the University of Pennsylvania where he made most of his contributions in psychology. He was trapped in Europe by World War I and never returned to the United States. Myriad hardships forced him to abandon his original project of a study of the entire field of probability and its application to other sciences. Whenever possible, however, he pursued his interests in psychometry and psychophysics and strove to remain active in psychology.