Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Testing for cirrhosis.

Cirrhosis can be suspected by a thorough clinical assessment, but compensated liver disease is often asymptomatic. Select investigations are therefore critical for identifying patients with advanced liver disease and cirrhosis Biomarkers and validated serum tests can evaluate liver damage and synthetic function. The ratio of the concentration of aspartate aminotransferase to the platelet count can predict the presence of cirrhosis Non-invasive imaging techniques, from basic ultrasound to elastography, are critical adjuncts to the clinical assessment of cirrhosis. They reduce the need for liver biopsy Careful monitoring, prescribing and appropriate specialist referral are key considerations in cirrhosis management. Early diagnosis can help to improve the outcomes for patients.

Expression of DNA methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA methyltransferases and associated proteins.

PURPOSE: The DNA methylation mediated by specific DNA methyltransferases (DNMTs), results in the epigenetic silencing of multiple genes which are implicated in human breast cancer. We hypothesized that the natural compounds modulate the expression of DNMTs and their associated proteins in the breast cancer cell lines and affect the methylation mediated gene silencing. METHODS: The DNMTs transcript expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in the tumors and the adjacent normal breast tissues of the patients with invasive ductal breast carcinoma. We tested the hypothesis that the natural compounds, viz., epigallocatechin gallate (EGCG), genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have demethylation potential. To investigate this hypothesis, we analyzed the DNMTs expression at the transcript levels, followed by the analysis of DNMT1 and its associated proteins (HDAC1, MeCP2, and MBD2). RESULTS: The increased DNMTs transcripts expression, viz., DNMT1, DNMT3a, and DNMT3b, in the breast cancer tissues suggest involvement of the DNMTs in the breast carcinogenesis. Quantitative RT-PCR analysis revealed that the treatment with natural compounds, viz., EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, resulted in a significant decrease in the transcript levels of all the DNMTs investigated. Importantly, these natural compounds decreased the protein levels of DNMT1, HDAC1, and MeCP2. CONCLUSION: Our results demonstrate that the natural compounds, EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have the potential to reverse the epigenetic changes. Moreover, their lack of toxicity makes these natural compounds promising candidates for the chemoprevention of the breast cancer. In-depth future mechanistic studies aimed to elucidate how these compounds affect the gene transcription are warranted.

Large-area flexible 3D optical negative index metamaterial formed by nanotransfer printing.

Negative-index metamaterials (NIMs) are engineered structures with optical properties that cannot be obtained in naturally occurring materials. Recent work has demonstrated that focused ion beam and layer-by-layer electron-beam lithography can be used to pattern the necessary nanoscale features over small areas (hundreds of µm(2)) for metamaterials with three-dimensional layouts and interesting characteristics, including negative-index behaviour in the optical regime. A key challenge is in the fabrication of such three-dimensional NIMs with sizes and at throughputs necessary for many realistic applications (including lenses, resonators and other photonic components). We report a simple printing approach capable of forming large-area, high-quality NIMs with three-dimensional, multilayer formats. Here, a silicon wafer with deep, nanoscale patterns of surface relief serves as a reusable stamp. Blanket deposition of alternating layers of silver and magnesium fluoride onto such a stamp represents a process for 'inking' it with thick, multilayer assemblies. Transfer printing this ink material onto rigid or flexible substrates completes the fabrication in a high-throughput manner. Experimental measurements and simulation results show that macroscale, three-dimensional NIMs (>75 cm(2)) nano-manufactured in this way exhibit a strong, negative index of refraction in the near-infrared spectral range, with excellent figures of merit.

Inverse design for phase mask lithography.

We have developed a method for designing the diffractive optics used in phase mask lithography. Genetic algorithms were used to inverse-design a grating's relief profile and associated exposure conditions so that desired periodic structures are formed. An experimentally promising grating designed to produce helices is demonstrated.

Fabrication and electrical conductivity of poly(methyl methacrylate) (PMMA)/carbon black (CB) composites: comparison between an ordered carbon black nanowire-like segregated structure and a randomly dispersed carbon black nanostructure.

Poly(methyl methacrylate) (PMMA)/carbon black (CB) composites were fabricated using two different mixing methods: (1) mechanical mixing and (2) solution mixing of the precursors, followed by compression molding. The microstructures obtained were examined by optical and scanning electron microscopy. Electrical properties were measured using impedance spectroscopy over a wide frequency range (10(-3) to +10(9) Hz). With the mechanical mixing method, a segregated structure is produced with PMMA particles forming faceted grains with carbon black particles aligning to form a network of 3D-interconnected nanowires. This microstructure allows percolation to occur at a low volume fraction of 0.26 vol % CB. In contrast, specimens made by the solution method have a microstructure where carbon black is distributed more randomly throughout the bulk, and thus, the percolation threshold is higher (2.7 vol % CB). The electrical properties of the PMMA/CB composites fabricated by the mechanical mixing method are comparable to those obtained with single-wall nanotubes as fillers.

Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children.

OBJECTIVES: In developed countries, small bowel histology in coeliac disease is a spectrum, ranging from normal with increased intraepithelial lymphocytes to the classic flat mucosa. In developing countries, mild to moderate enteropathies in children with chronic diarrhea and growth failure are assumed to be caused by tropical sprue, persistent infections, or malnutrition with bacterial overgrowth. We report the prevalence and histology of coeliac disease in children with chronic diarrhea at a tertiary referral hospital in North India. METHODS: Two hundred fifty-nine children with symptoms indicating coeliac disease attended the All India Institute of Medical Sciences. Histology was graded after a modified Marsh classification. Serum immunoglobulin A anti-endomysial antibodies (AEA) were assayed using indirect immunofluorescence. Subjects with abnormal histology and positive AEA were put on a gluten free diet (GFD). Coeliac disease was diagnosed on small intestinal biopsy changes and a clinical response to a GFD. RESULTS: Severe enteropathies were present in 63 (24%) subjects, and 58 (92%) responded to a GFD. Sixty-six (25%) had moderate histologic changes, 61 responding to a GFD. AEA was positive in 56 of 63 patients with severe and 65 of 66 with moderate enteropathies. Fifty-seven children had mild enteropathies, and 19 of 20 with positive AEA responded clinically to a GFD. CONCLUSIONS: Coeliac disease is more common than previously believed. It presents a variable histology, and diagnoses may be missed or delayed if based only on severe enteropathies. Serology is a useful adjunct to diagnosis, and diagnostic criteria need to be developed appropriately for coeliac disease in developing countries despite limited facilities.