Radiogenomic biomarkers for immunotherapy in glioblastoma: A systematic review of magnetic resonance imaging studies.

Background: Immunotherapy is an effective "precision medicine" treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma. Methods: A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered: CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis. Results: Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed. Conclusions: Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.

Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme.

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). Homologous recombination deficiency was identified in 40% of high-grade serous ovarian cancer cases with 30% linked to pathogenic germline variants, highlighting the value of combined somatic and germline analysis. The linkage of WGS and longitudinal life course clinical data allowed the assessment of treatment outcomes for patients stratified according to pangenomic markers. Our findings demonstrate the utility of linking genomic and real-world clinical data to enable survival analysis to identify cancer genes that affect prognosis and advance our understanding of how cancer genomics impacts patient outcomes.

Electrochemical Redox Cycling Behavior of Gold Nanoring Electrodes Microfabricated on a Silicon Micropillar.

We report the microfabrication and characterization of concentric gold nanoring electrodes (Au NREs), which were fabricated by patterning two gold nanoelectrodes on the same silicon (Si) micropillar tip. Au NREs of 165 ± 10 nm in width were micropatterned on a 6.5 ± 0.2 µm diameter 80 ± 0.5 µm height Si micropillar with an intervening ~ 100 nm thick hafnium oxide insulating layer between the two nanoelectrodes. Excellent cylindricality of the micropillar with vertical sidewalls as well as a completely intact layer of a concentric Au NRE including the entire micropillar perimeter has been achieved as observed via scanning electron microscopy and energy dispersive spectroscopy data. The electrochemical behavior of the Au NREs was characterized by steady-state cyclic voltammetry and electrochemical impedance spectroscopy. The applicability of Au NREs to electrochemical sensing was demonstrated by redox cycling with the ferro/ferricyanide redox couple. The redox cycling amplified the currents by 1.63-fold with a collection efficiency of > 90% on a single collection cycle. The proposed micro-nanofabrication approach with further optimization studies shows great promise for the creation and expansion of concentric 3D NRE arrays with controllable width and nanometer spacing for electroanalytical research and applications such as single-cell analysis and advanced biological and neurochemical sensing.

Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters: Optimization and In Vivo Studies.

Imbalances in levels of glutamate (GLU) and gamma-aminobutyric acid (GABA) and their sub-second signaling dynamics occur in several brain disorders including traumatic brain injury, epilepsy, and Alzheimer's disease. The present work reports on the optimization and in vivo testing of a silicon (Si) multifunctional biosensor probe for sub-second simultaneous real-time detection of GLU and GABA. The Si probe features four surface-functionalized platinum ultramicroelectrodes (UMEs) for detection of GLU and GABA, a sentinel site, and integrated microfluidics for in-situ calibration. Optimal enzyme concentrations, size-exclusion phenylenediamine layer and micro spotting conditions were systematically investigated. The measured GLU sensitivity for the GLU and GABA sites were as high as 219 ± 8 nA µM-1 cm-2 (n = 3). The measured GABA sensitivity was as high as 10 ± 1 nA µM-1 cm-2 (n = 3). Baseline recordings (n = 18) in live rats demonstrated a useful probe life of at least 11 days with GLU and GABA concentrations changing at the levels of 100's and 1000's of µM and with expected periodic bursts or fluctuations during walking, teeth grinding and other activities and with a clear difference in the peak amplitude of the sensor fluctuations between rest (low) and activity (higher), or when the rat was surprised (a reaction with no movement). Importantly, the probe could improve methods for large-scale monitoring of neurochemical activity and network function in disease and injury, in live rodent brain.

Whole-genome sequencing reveals host factors underlying critical COVID-19.

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

In Vitro Electrochemical Detection of Hydrogen Peroxide in Activated Macrophages via a Platinum Microelectrode Array.

Oxidative stress, an excess of endogenous or exogenous reactive oxygen species (ROS) in the human body, is closely aligned with inflammatory responses. ROS such as hydrogen peroxide (H2O2), superoxide, and radical hydroxyl ions serve essential functions in fighting infection; however, chronic elevation of these species irreversibly damages cellular components. Given the central role of inflammation in a variety of diseases, including Alzheimer's disease and rheumatoid arthritis, a low-cost, extracellular, non-invasive assay of H2O2 measurement is needed. This work reports the use of a platinum microelectrode array (Pt MEA)-based ceramic probe to detect time- and concentration-dependent variations in H2O2 production by activated RAW 264.7 macrophages. First, these cells were activated by lipopolysaccharide (LPS) to induce oxidative stress. Chronoamperometry was then employed to detect the quantity of H2O2 released by cells at various time intervals up to 48 h. The most stimulatory concentration of LPS was identified. Further experiments assessed the anti-inflammatory effect of dexamethasone (Dex), a commonly prescribed steroid medication. As expected, the probe detected significantly increased H2O2 production by LPS-doped macrophages, subsequently diminishing the pro-inflammatory effect in LPS-doped cells treated with Dex. These results strongly support the use of this probe as a non-invasive, robust, point-of-care test of inflammation, with a high potential for multiplexing in further studies.

Nafion and Multiwall Carbon Nanotube Modified Ultrananocrystalline Diamond Microelectrodes for Detection of Dopamine and Serotonin.

Neurochemicals play a critical role in the function of the human brain in healthy and diseased states. Here, we have investigated three types of microelectrodes, namely boron-doped ultrananocrystalline diamond (BDUNCD), nafion-modified BDUNCD, and nafion-multi-walled carbon nanotube (MWCNT)-modified BDUNCD microelectrodes for long-term neurochemical detection. A ~50 nm-thick nafion-200-nm-thick MWCNT-modified BDUNCD microelectrode provided an excellent combination of sensitivity and selectivity for the detection of dopamine (DA; 6.75 µA µM-1 cm-2) and serotonin (5-HT; 4.55 µA µM-1 cm-2) in the presence of excess amounts of ascorbic acid (AA), the most common interferent. Surface stability studies employing droplet-based microfluidics demonstrate rapid response time (<2 s) and low limits of detection (5.4 ± 0.40 nM). Furthermore, we observed distinguishable DA and 5-HT current peaks in a ternary mixture during long-term stability studies (up to 9 h) with nafion-MWCNT-modified BDUNCD microelectrodes. Reduced fouling on the modified BDUNCD microelectrode surface offers significant advantages for their use in long-term neurochemical detection as compared to those of prior-art microelectrodes.

Brain-Implantable Multifunctional Probe for Simultaneous Detection of Glutamate and GABA Neurotransmitters.

Glutamate (GLU) and gamma-aminobutyric acid (GABA) are neurotransmitters (NTs) with an essential role in signal transmission in the brain. Brain disorders, such as epilepsy, Alzheimer's and Parkinson's diseases, and traumatic brain injury can be linked to imbalances in the GLU-GABA homeostasis that occurs in sub-second to seconds time frames. Current measurement techniques can detect these two NT concentrations simultaneously only in vitro. The present work reports on the fabrication of a silicon multifunctional biosensor microarray probe for sub-second simultaneous GLU-GABA detection in real-time, with excellent analyte sensitivity and selectivity and in vivo capabilities. The novel Si probes feature four surface-functionalized platinum ultramicroelectrodes (UMEs) for simultaneous amperometric detection of GLU and GABA with a sentinel, and a built-in microfluidic channel for the introduction of neurochemicals in the proximity of the UMEs. The microchannel also allows functioning of an On-Demand In-situ Calibrator that runs in-situ biosensor calibration. The probe exhibited excellent robustness at insertion in agarose-gel brain-tissue-mimicking test, and remarkably high hydrogen peroxide sensitivity (a by-product of GLU-GABA enzyme biosensor) with values on the order of 5000 nA µM -1 cm -2 and maximum sensitivities of 204±15 nA µM -1 cm -2 and 37±7 nA µM -1 cm -2 for GLU and GABA, respectively. Furthermore, the limit of detection of the biosensors reached as low as 7 nM, 165 nM and 750 nM for H 2 O 2, GLU and GABA, respectively and a temporal resolution of hundreds of milliseconds during in vivo studies using freely moving rats.

Novel microwire-based biosensor probe for simultaneous real-time measurement of glutamate and GABA dynamics in vitro and in vivo.

Glutamate (GLU) and γ-aminobutyric acid (GABA) are the major excitatory (E) and inhibitory (I) neurotransmitters in the brain, respectively. Dysregulation of the E/I ratio is associated with numerous neurological disorders. Enzyme-based microelectrode array biosensors present the potential for improved biocompatibility, localized sample volumes, and much faster sampling rates over existing measurement methods. However, enzymes degrade over time. To overcome the time limitation of permanently implanted microbiosensors, we created a microwire-based biosensor that can be periodically inserted into a permanently implanted cannula. Biosensor coatings were based on our previously developed GLU and reagent-free GABA shank-type biosensor. In addition, the microwire biosensors were in the same geometric plane for the improved acquisition of signals in planar tissue including rodent brain slices, cultured cells, and brain regions with laminar structure. We measured real-time dynamics of GLU and GABA in rat hippocampal slices and observed a significant, nonlinear shift in the E/I ratio from excitatory to inhibitory dominance as electrical stimulation frequency increased from 10 to 140 Hz, suggesting that GABA release is a component of a homeostatic mechanism in the hippocampus to prevent excitotoxic damage. Additionally, we recorded from a freely moving rat over fourteen weeks, inserting fresh biosensors each time, thus demonstrating that the microwire biosensor overcomes the time limitation of permanently implanted biosensors and that the biosensors detect relevant changes in GLU and GABA levels that are consistent with various behaviors.

Surface Fouling of Ultrananocrystalline Diamond Microelectrodes during Dopamine Detection: Improving Lifetime via Electrochemical Cycling.

In this work, we report the electrochemical response of a boron-doped ultrananocrystalline diamond (BDUNCD) microelectrode during long-term dopamine (DA) detection. Specifically, changes to its electrochemical activity and electroactive area due to DA byproducts and surface oxidation are studied via scanning electron microscopy, energy dispersive spectroscopy, electrochemical impedance spectroscopy, and silver deposition imaging (SDI). The fouling studies with amperometry (AM) and fast scan cyclic voltammetry (FSCV) methods suggest that the microelectrodes are heavily fouled due to poor DA-dopamine- o-quinone cyclization rates followed by a combination of polymer formation and major changes in their surface chemistry. SDI data confirms the presence of the insulating polymer with sparsely distributed tiny electroactive regions. This resulted in severely distorted DA signals and a 90% loss in signal starting as early as 3 h for AM and a 56% loss at 6.5 h for FSCV. This underscores the need for cleaning of the fouled microelectrodes if they have to be used long-term. Out of the three in vivo suitable electrochemical cycling cleaning waveforms investigated, the standard waveform (-0.4 V to +1.0 V) provides the best cleaned surface with a fully retained voltammogram shape, no hysteresis, no DA signal loss (a 90 ± 0.72 nA increase), and the smallest charge transfer resistance value of 0.4 ± 0.02 MΩ even after 6.5 h of monitoring. Most importantly, this is the same waveform that is widely used for in vivo detection with carbon fiber microelectrodes. Future work to test these microelectrodes for more than 24 h of DA detection is anticipated.

An enzyme-based electrochemical biosensor probe with sensitivity to detect astrocytic versus glioma uptake of glutamate in real time in vitro.

Glutamate, a major excitatory neurotransmitter in the central nervous system, is essential for regulation of thought, movement, memory, and other higher functions controlled by the brain. Dysregulation of glutamate signaling is associated with severe neuropathological conditions, such as epilepsy, and glioma, a form of brain cancer. Glutamate signals are currently detected by several types of neurochemical probes ranging from microdialysis-based to enzyme-based carbon fiber microsensors. However, an important technology gap exists in the ability to measure glutamate dynamics continuously, and in real time, and from multiple locations in the brain, which limits our ability to further understand the involved spatiotemporal mechanisms of underlying neuropathologies. To overcome this limitation, we developed an enzymatic glutamate microbiosensor, in the form of a ceramic-substrate enabled platinum microelectrode array, that continuously, in real time, measures changes in glutamate concentration from multiple recording sites. In addition, the developed microbiosensor is almost four-fold more sensitive to glutamate than enzymatic sensors previously reported in the literature. Further analysis of glutamate dynamics recorded by our microbiosensor in cultured astrocytes (control condition) and glioma cells (pathological condition) clearly distinguished normal versus impaired glutamate uptake, respectively. These results confirm that the developed glutamate microbiosensor array can become a useful tool in monitoring and understanding glutamate signaling and its regulation in normal and pathological conditions. Furthermore, the developed microbiosensor can be used to measure the effects of potential therapeutic drugs to treat a range of neurological diseases.

A Novel Microbiosensor Microarray for Continuous ex Vivo Monitoring of Gamma-Aminobutyric Acid in Real-Time.

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for in vivo studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, H2O2) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method requires a rather cumbersome process with prereactors and relies on externally applied reagents. Here, we report the design and implementation of a GABA microarray probe that operates on a newly conceived principle. It consists of two microbiosensors, one for glutamate (Glu) and one for GABA detection, modified with glutamate oxidase and GABASE enzymes, respectively. By simultaneously measuring and subtracting the H2O2 oxidation currents generated from these microbiosensors, GABA and Glu can be detected continuously in real-time in vitro and ex vivo and without the addition of any externally applied reagents. The detection of GABA by this probe is based upon the in-situ generation of α-ketoglutarate from the Glu oxidation that takes place at the Glu microbiosensor. A GABA sensitivity of 36 ± 2.5 pA µM-1cm-2, which is 26-fold higher than reported in the literature, and a limit of detection of 2 ± 0.12 µM were achieved in an in vitro setting. The GABA probe was successfully tested in an adult rat brain slice preparation. These results demonstrate that the developed GABA probe constitutes a novel and powerful neuroscientific tool that could be employed in the future for in vivo longitudinal studies of the combined role of GABA and Glu (a major excitatory neurotransmitter) signaling in brain disorders, such as epilepsy and traumatic brain injury, as well as in preclinical trials of potential therapeutic agents for the treatment of these disorders.

Detection of neurochemicals with enhanced sensitivity and selectivity via hybrid multiwall carbon nanotube-ultrananocrystalline diamond microelectrodes.

Abnormal neurochemical signaling is often the underlying cause of brain disorders. Electrochemical microsensors are widely used to monitor neurochemicals with high spatial-temporal resolution. However, they rely on carbon fiber microelectrodes that often limit their sensing performance. In this study, we demonstrate the potential of a hybrid multiwall carbon nanotube (MWCNT) film modified boron-doped ultrananocrystalline diamond (UNCD) microelectrode (250 µm diameter) microsensor for improved detection of dopamine (DA) in the presence of common interferents. A series of modified microelectrodes with varying film thicknesses were microfabricated by electrophoretic deposition (EPD) and characterized by scanning electron microscopy, x-ray photoelectron spectroscopy, electrochemical impedance spectroscopy (EIS) and silver deposition imaging. Using cyclic voltammetry, the 100-nm "thin" film microelectrode produced the most favorable combination of DA sensitivity value of 36 ±2% µA/µM/cm2 with a linear range of 33 nM to 1 µM and a limit of detection (LOD) of 9.5 ± 1.2% nM. The EIS spectra of these microelectrodes revealed three regions with inhomogeneous pore geometry and differing impedance values and electrochemical activity, which was found to be film thickness dependent. Using differential pulse voltammetry, the modified microelectrode showed excellent selectivity by exhibiting three distinct peaks for the DA, serotonin and excess ascorbic acid in a ternary mixture. These results provide two key benefits: first, remarkable improvements in DA sensitivity (>125-fold), selectivity (>2000-fold) and LOD (>180-fold), second, these MWCNTs can be selectively coated with a simple, scalable and low cost EPD process for highly multiplexed microsensor technologies. These advances offer considerable promise for further progress in chemical neurosciences.

PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration.

It has been reported that p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer tissue. PAK4 is a member of the PAK family of serine/threonine kinases, which act as effectors for several small GTPases, and has been specifically identified to function downstream of HGF-mediated c-Met activation in a PI3K dependent manner. However, the functionality of PAK4 in pancreatic cancer and the contribution made by HGF signalling to pancreatic cancer cell motility remain to be elucidated. We now find that elevated PAK4 expression is coincident with increased expression levels of c-Met and the p85α subunit of PI3K. Furthermore, we demonstrate that pancreatic cancer cells have a specific motility response to HGF both in 2D and 3D physiomimetic organotypic assays; which can be suppressed by inhibition of PI3K. Significantly, we report a specific interaction between PAK4 and p85α and find that PAK4 deficient cells exhibit a reduction in Akt phosphorylation downstream of HGF signalling. These results implicate a novel role for PAK4 within the PI3K pathway via interaction with p85α. Thus, PAK4 could be an essential player in PDAC progression representing an interesting therapeutic opportunity.

Expression of polymeric immunoglobulin receptor and stromal activity in pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: Polymeric immunoglobulin receptor (pIgR) traffics Immunoglobulins (IgA and IgM) through epithelial cells in normal mucosae but neither are expressed in the normal pancreas. Recent work from our laboratory suggested pIgR may be upregulated in pancreatic ductal adenocarcinoma (PDAC). Our aim was to assess the role of pIgR in human PDAC. METHODS: pIgR expression was manipulated (siRNA and shRNA) in cell lines to evaluate its subsequent effect on cell behaviour in 2D assays as well as 3D organotypics models. Tissue Microarrays of 88 patients with PDAC were analysed after pIgR, αSMA, E-Cadherin and Picrosirius Red staining to assess their role as a combined bio-marker panel. RESULTS: Cytokines such as interleukin 4 (IL4) and Tumour Necrosis Factor (TNFα) could not modulate pIgR expression in PDAC cell lines despite this effect being seen in other studies. Down-regulation in pIgR expression in Capan1 cancer cell line resulted in reduction of cellular proliferation, adhesion and migration in 2D assays. In 3D physiomimetic organotypic models, pIgR downregulation resulted in reduced cancer cell invasion, alteration of apico-basal polarity and diminished stromal activity. In human PDAC, decreased E-cadherin expression correlates with increased pIgR expression through pancreatic intra-epithelial neoplasia (PanIN) progression. In combination with enhanced stromal indices (α-smooth muscle action (SMA) and Picrosirius red), low pIgR scores had a trend towards better survival. CONCLUSION: pIgR may be involved in PDAC progression and may be linked stromal activity. Further work on its precise role is mandated in in vivo models, to understand its influence on cancer progression.

The role of perioperative inflammatory-based prognostic systems in patients with colorectal liver metastases undergoing surgery. A cohort study.

BACKGROUND: We aim to evaluate the prognostic value of preoperative and postoperative inflammatory systems in patients who had undergone surgery for colorectal liver metastases, focusing our analysis on the role of C-reactive protein-to-albumin ratio (CAR) and Glasgow prognostic score (GPS). METHODS: A total of 194 patients were enrolled onto this study. Demographics, tumor-related variables, preoperative and postoperative (day 1) inflammatory variables were analyzed as potential prognostic factors. RESULTS: For the whole cohort three and 5-year survival were 68% and 53% respectively. Median follow up was 27 months (IQR 10-42). At multivariate analysis only preoperative GPS (HR 12.06, 95% CI 2.82-51.53; p = 0.0008) was an independent risk factor for poor survival. Patients with a preoperative GPS = 0 had a 3-years survival of 70% while it was 33% for those with GPS = 1 (p < 0.0001). In patients with preoperative GPS = 0 preoperative CAR (HR 1.19, 95%CI 1.05-1.35; p = 0.0059) could identify a sub-population at risk for reduced survival. The optimal cut-off for preoperative CAR (preCAR) was 0.133 (HR 7.11 95% CI 1.37-36.78, p = 0.0063). 3-years survival was 75% and 21% for patients with preCAR>0.133 and ≤ 0.133, respectively (p = 0.0005). The immediate postoperative inflammatory status did not have a significant impact on survival. CONCLUSION: GPS is a significant prognostic factor in patients with colorectal liver metastases undergoing surgery. CAR could be a valuable tool to further stratify patients with preoperative GPS = 0 according to their prognosis.

Lymphoepithelial Cyst of the Pancreas.

Lymphoepithelial cyst (LEC) of the pancreas is an extremely rare, benign pancreatic cystic lesion that is difficult to differentiate preoperatively from other cystic pancreatic lesions. LEC may have malignant potential. Here, we describe a case of LEC of the pancreas - initially suspected to be a mucinous cyst neoplasm - in an elderly man presenting with abdominal pain, who went on to have a distal pancreatectomy and splenectomy. We also review the relevant literature and discuss implications for the diagnosis and management of this rare lesion.

Role of laparoscopy in hepatobiliary malignancies.

The many benefits of laparoscopy, including smaller incision, reduced length of hospital stay and more rapid return to normal function, have seen its popularity grow in recent years. With concurrent improvements in non-surgical cancer management the importance of accurate staging is becoming increasingly important. There are two main applications of laparoscopic surgery in managing hepato-pancreatico-biliary (HPB) malignancy: accurate staging of disease and resection. We aim to summarize the use of laparoscopy in these contexts. The role of staging laparoscopy has become routine in certain cancers, in particular T[2] staged, locally advanced gastric cancer, hilar cholangiocarcinoma and non-Hodgkin's lymphoma. For other cancers, in particular colorectal, laparoscopy has now become the gold standard management for resection such that there is no role for stand-alone staging laparoscopy. In HPB cancers, although staging laparoscopy may play a role, with ever improving radiology, its role remains controversial.