Screening and Management of Hepatocellular Carcinoma: The Australian Perspective

Hepatocellular cancer (HCC) remains relatively uncommon in Australia, however incidence rates have been progressively rising, as in many other western countries, over the last few decades. Currently, chronic hepatitis B (HBV) or hepatitis C (HCV) infections accounts for the majority of primary liver cancers, but as the incidence of HBV declines with the implementation of immunization programs and HCV is eradicated by direct acting anti viral therapies, more cases will be due to metabolic causes such as non-alcoholic fatty liver disease. The cornerstone of management involves identifying potential risk factors and implementing both preventative and therapeutic strategies. As we gain more knowledge about the pathogenesis of HCC, newer agents such as multikinase inhibtors have been developed to target specific pathways and have been shown to delay time to disease progression. Well defined screening, diagnostic and management algorithms will allow for standardisation of protocols and enable classification of patients and treatment modalities offering some prediction of outcome and prognosis. It is anticipated that effective screening and surveillance programs will enable the detection of tumours at an early stage thereby allowing for a wider range of therapeutic options with improved outcomes.     

Rhabdomyolysis in Bariatric Surgery: a Systematic Review

Background

Rhabdomyolysis (RML) is a rare complication of bariatric surgery. A systematic review was performed to identify risk factors and patient outcomes in morbidly obese patients undergoing bariatric surgery who develop RML.

Methods

A comprehensive search was performed between January 1990 and March 2012 using relevant MeSH terms. Studies were chosen based on predefined inclusion criteria. RML was defined as a creatine kinase of more than 1,000 IU/L. The parameters assessed included patient characteristics of the RML population, type of bariatric surgery performed, operating time, complications, presentation and diagnosis of RML.

Results

Twenty-two studies were analysed which included 11 case reports, two case series, six prospective and three retrospective comparative studies. Overall 145 patients with RML were reported following bariatric surgery. Acute renal failure was found in 20 patients (14 %) and was significantly more likely to occur in patients with postoperative muscle pain (p?<?0.05). The mortality rate after renal failure was 25 % (n?=?5). In the comparative studies, 87 RML patients were compared with 325 non-RML patients. The RML patients were more likely to be male, had a greater mean body mass index (BMI) (52 vs 48 kg/m², p?<?0.01) and underwent a longer operation (255 vs 207 min, p?<?0.01) compared to non-RML patients.

Conclusions

Risk factors of developing RML following bariatric surgery include male gender, elevated BMI and prolonged operating time. Patients with a biochemical diagnosis of RML and postoperative myalgia after bariatric surgery are at increased risk of developing acute renal failure and mortality. These patients must be identified and treated promptly.     

Assessment of Hemodialysis Adequacy by Ionic Dialysance: Comparison to Standard Method of Urea Removal

Background. The hemodialysis adequacy is one of the most important issues influencing the survival of patients on maintenance hemodialysis (HD). Assessment of measuring the delivered dialysis dose using clearance × time/volume (Kt/V) index requires multiple blood sampling. New methods for assessment of dialysis dose based on ionic dialysance (ID) have been suggested. Online conductivity monitoring (using sodium flux as a surrogate for urea) allows the repeated noninvasive measurement of Kt/V on each HD treatment. In this study we have compared this method with the standard method of estimating Kt/V. Methods. We studied 24 established HD patients over a 4 week time period. Patients were dialyzed using Fresenius 4008S dialysis monitors, equipped with modules to measure ID. Data were manually collected and analyzed using the appropriate statistical software. Urea removal (UR) was measured once a week by a two-pool calculation, estimating an eKt/V. Results. The Kt/V measured by ID highly correlated with the one derived from the measurement of the UR (r = 0.8959, p< 0.0001). The ID underestimated UR by the mean of 6%. The ID varied greatly within individual patients with a median of 1.29 ± 0.22. If the eKt/V ≥ 1.2 is considered adequate, 33% of the patients would have been inadequately dialyzed. The mean HD duration to achieve an adequate dialysis was 4 hours and 47 minutes with high interpatient variability. Conclusion. The ID seems to be an easily obtained measure of the delivered dialysis dose, correlating well with standard UR method. Substantial individual variations imply that repeated measures (ideally for all treatments) are necessary to obtain a real answer to the mean treatment dose being delivered to the patients.     

Imaging signs in idiopathic intracranial hypertension: Are these signs seen in secondary intracranial hypertension too?

Background:

The purpose of this study was to evaluate the difference in the occurrence of the various “traditional” imaging signs of intracranial hypertension (IIH) on magnetic resonance imaging (MRI) in patients with idiopathic (IIH) and secondary intracranial hypertension.

Materials and Methods:

In a retrospective analysis, the MRI findings of 21 patients with IIH and 60 patients with secondary intracranial hypertension (41 with tumors; 19 with intracranial venous hypertension) were evaluated for the presence or absence of various “traditional” imaging signs of IIH (perioptic nerve sheath distention, vertical buckling of optic nerve, globe flattening, optic nerve head protrusion and empty sella) using the Fisher’s exact test. Odds ratios were also calculated. Statistical Package for the Social Sciences version 17.0 was used for statistical analysis. Subgroup analysis of the IIH versus tumors and IIH versus venous hypertension were performed.

Results:

Optic nerve head protrusion and globe flattening were significantly associated with IIH. There was no statistically significant difference in the occurrence of rest of the findings. On subgroup analysis, globe flattening and optic nerve head protrusion occurred significantly more often in IIH than in tumors. However, there was no statistically significant difference in the occurrence of any of these findings in patients with IIH and venous hypertension.

Conclusions:

IIH is a diagnosis of exclusion. While secondary causes of raised intracranial pressure (ICP) have obvious clinical findings on MRI, some conditions like cerebral venous thrombosis may have subtle signs and differentiating between primary and secondary causes may be difficult. In the absence of any evident cause of raised ICP, presence of optic nerve head protrusion or globe flattening can suggest the diagnosis of IIH.     

Evaluating computer-aided detection algorithms

Computer-aided detection (CAD) has been attracting extensive research interest during the last two decades. It is recognized that the full potential of CAD can only be realized by improving the performance and robustness of CAD algorithms and this requires good evaluation methodology that would permit CAD designers to optimize their algorithms. Free-response receiver operating characteristic (FROC) curves are widely used to assess CAD performance, however, evaluation rarely proceeds beyond determination of lesion localization fraction (sensitivity) at an arbitrarily selected value of nonlesion localizations (false marks) per image. This work describes a FROC curve fitting procedure that uses a recent model of visual search that serves as a framework for the free-response task. A maximum likelihood procedure for estimating the parameters of the model from free-response data and fitting CAD generated FROC curves was implemented. Procedures were implemented to estimate two figures of merit and associated statistics such as 95% confidence intervals and goodness of fit. One of the figures of merit does not require the arbitrary specification of an operating point at which to evaluate CAD performance. For comparison a related method termed initial detection and candidate analysis was also implemented that is applicable when all suspicious regions are reported. The two methods were tested on seven mammography CAD data sets and both yielded good to excellent fits. The search model approach has the advantage that it can potentially be applied to radiologist generated free-response data where not all suspicious regions are reported, only the ones that are deemed sufficiently suspicious to warrant clinical follow-up. This work represents the first practical application of the search model to an important evaluation problem in diagnostic radiology. Software based on this work is expected to benefit CAD developers working in diverse areas of medical imaging.     

Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes

The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG₂‐c(NGR), were synthesized, radiolabeled with ^99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of ^99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG₂ unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.