Alpha-fetoprotein detection of hepatocellular carcinoma leads to a standardized analysis of dynamic AFP to improve screening based detection

Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 04 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log10 -transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p-5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refineable algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance

Retrospective Multicenter Study on Outcome Measurement for Dyskinesia Improvement in Parkinson’s Disease Patients with Pallidal and Subthalamic Nucleus Deep Brain Stimulation

Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson’s disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-Ⅲ) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006)

Model coefficients obtained from full-data and windowed analyses in static mode (wave 48) and dynamic mode (wave 1).

<p>Model coefficients obtained from full-data and windowed analyses in static mode (wave 48) and dynamic mode (wave 1).</p

Case-controls study assessing the performance of our dynamic Bayesian algorithm for identifying HCV cases at higher risk of HCC-diagnosis during 2009–2014.

<p>Case-controls study assessing the performance of our dynamic Bayesian algorithm for identifying HCV cases at higher risk of HCC-diagnosis during 2009–2014.</p

Demographics and route to diagnosis in HCC patients.

<p>Demographics and route to diagnosis in HCC patients.</p

Dynamic AFP changes associated with HCC development.

<p><b>A</b>) Plotting each individual’s time course of serum AFP relative to diagnosis an elevation in values is observed prior to diagnosis. Here all individuals in the HCC review in whom AFP influenced clinical management (n = 49) are charted with AFP on a log₁₀ scale. <b>B</b>) Graphic demonstrates the concept of gradient and intercept over a specific individual’s time course. <b>C</b>) The screening cohort of 1509 patients followed over time for development of HCC, overall incidence at end of index screening (1186 days from 01/01/2009, total HCC free % = 93.7).</p

Exploratory analysis of HCC surveillance cohort.

<p>Exploratory analysis of HCC surveillance cohort.</p

AFP as an HCC surveillance tool detects a significant number of treatable HCC in patients with satisfactory outcomes.

<p><b>A</b>) Survival for total HCC cohort diagnosed with HCC between 1/1/2009 and 31/12/2014. <b>B</b>) The role of AFP in HCC detection. Method of HCC detection for the 133 patients within HCC surveillance programme at the time of diagnosis, chequered area within AFP pickup group represents the 28/49 patients in whom a recent US had not been performed—see text for details. <b>C</b>) Individual AFP levels at time of diagnosis for patients diagnosed with HCC, AFP values plotted at log10; AFP = 6 (local ULN; yellow) and AFP = 20 (red) are shown. All columns p<0.0001 to one another by Kruskal Wallis test with Dunns multiple comparison. <b>D</b>) Survival of patients with HCC diagnosed through surveillance screening either through US or AFP mediated conversion to CT/MRI imaging, error bars = SEM, p value denotes Mantel Cox. <b>E</b>) Therapy offered to patients within each group (US detected n = 61 and AFP detected n = 49) of patients with HCC detected during surveillance; all p>0.05 by 2 way Anova. Of the 11 and 9 patients listed for liver transplantation, 2 (due to tumour growth) and 1 (due to frailty) were delisted from the waiting list whilst awaiting transplantation in US and AFP detected groups respectively.</p