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Purpose of Review Gastroenteropancreatic NEN (GEP-NEN) are group of malignancies with significant clinical, anatomical and molecular heterogeneity. High-grade GEP-NEN in particular present unique management challenges. Recent Findings In the current era, multidisciplinary management with access to a combination of functional imaging and targeted molecular profiling can provide important disease characterisation, guide individualised management and improve patient outcome. Multiple treatment options are now available, and combination and novel therapies are being explored in clinical trials. Summary Precision medicine is highly relevant for a heterogenous disease like NEN. The integration of dual-tracer functional PET/CT imaging, molecular histopathology and genomic data has the potential to be used to gain a more comprehensive understanding of an individual patient’s disease biology for precision diagnosis, prognostication and optimal treatment allocation.

The modern era of radioiodine (I-131) theranostics for metastatic differentiated thyroid cancer requires us to rationalize the role of traditional empiric prescription in nonmalignant thyroid disease. We currently practice empiric I-131 prescription for treatment of hyperthyroidism. This study aims to assess outcomes after treatment of hyperthyroidism by empiric I-131 prescription at our centre, evaluate factors that impact on outcomes and prescribing practice, and gain insight into whether there is a place for theranostically-guided prescription in hyperthyroidism.A retrospective review was undertaken of all patients with Graves' disease, toxic multinodular goitre (MNG) and toxic adenoma treated with I-131 between 2016 and 2021. Associations between clinical or scintigraphic variables and remission (euthyroid or hypothyroid) or persistence of hyperthyroidism at follow-up were performed using standard t test as well as Pearson's product correlation.Of 146 patients with a mean follow-up of 13.6 months, 80.8% achieved remission of hyperthyroidism. This was highest in toxic nodules (90.1%), compared with Graves' disease (73.8%) and toxic MNG (75.5%). In patients with Graves' disease, higher administered activity was associated with remission (p = .035). There was a weak inverse correlation between the Tc-99m pertechnetate uptake vs prescribed activity in Graves' disease (r = -0.33; p = .009). Only one patient (0.7%) had an I-131 induced flare of thyrotoxicosis.Traditional empiric I-131 prescription is a safe and effective treatment of hyperthyroidism and suitable for most patients. However, there may be a role for personalized I-131 prescription by theranostic guidance in selected patients with high thyroid hyperactivity.

Background: The diagnosis of diabetes insipidus (DI) relies on indirect measurement of serum and urine sodium and osmolality. Since the diagnosis can only be made when an inappropriately dilute urine is paired with a significantly concentrated serum, the process is tedious for the clinician and uncomfortable for the patient. Copeptin is the C-terminal portion of the anti-diuretic hormone (ADH) prohormone which correlates with the less stable ADH, therefore providing a direct measurement of posterior pituitary response to hyperosmolar stress. (1,2) Aim: This study aims to assess the diagnostic accuracy of copeptin in patients with central DI compared with subjects who underwent pituitary surgery without developing DI. Methods: Serum samples from subjects with central DI, control subjects post pituitary surgery with no DI (NDI) and control subjects with SIADH were collected and analysed on the BRAHMS KRYPTOR copeptin assay. Groups were compared using unpaired T-test and Levene’s test for equal variance. Results: 56 samples from 22 subjects (13 females, 9 males, mean age 53.9 ± 15.5 y.o.) were analysed. Two subjects had resolved DI (RDI) after copeptin analysis and were successfully weaned off DDAVP and reclassified as NDI. Of the DI subjects, 1 had acute and 5 had chronic DI. Copeptin was lower in DI compared to NDI group (p = 0.013), while serum sodium, osmolality, urine osmolality were similar. Copeptin did not differentiate between the SIADH and NDI groups. After exclusion of NDI samples with serum sodium ≤ 140 mmol/L, the area under the curve was 0.97 (95% CI 0.9 to 1.0), a copeptin cut-off of 2.9 pmol/L predicts DI with a sensitivity of 92% and a specificity of 90%. Conclusion: Copeptin concentration of < 3.0 pmol/L concurrently with serum sodium concentration of > 140mmol/L predicted central DI when using post pituitary surgery subjects without DI as controls. 1. Winzeler, B., Zweifel, C., Nigro, N., Arici, B., Bally, M., Schuetz, P., Blum, C., Kelly, C., Berkmann, S., Huber, A., Gentili, F., Zadeh, G., Landolt, H., Mariani, L., Müller, B. and Christ-Crain, M. (2015). Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery. The Journal of Clinical Endocrinology & Metabolism, 100(6), pp.2275-2282. 2. Fenske, J., Refardt, I., SchnyderI., Winzeler, B., Drummond J., Ribeiro-Oliveira, Jr. A., Drescher, T., Bilz S., Vogt, D.R., Malzahn, U., Kroiss, M., Christ, E., Henzen, C., Fischli S., Tönjes, A., Mueller, B., Schopohl, J., Flitsch, J., Brabant, G., Fassnacht M., Christ-Crain, M. (2018). Copeptin in the Diagnosis of Diabetes Insipidus. New England Journal of Medicine, 379(18), pp.1784-1786.

We describe three cases of severe hyponatraemia in the setting of primary polydipsia that were managed in our centre in 2016. Despite receiving different solute loads, large volume diuresis and rapid correction of serum sodium occurred in all cases. Given the potentially catastrophic consequence of osmotic demyelination, we highlight the judicious use of desmopressin and hypotonic fluid infusion to mitigate sodium overcorrection in this setting.

The inverse-square law pops up all over. It’s a simplified model of reality that describes light, sound, gravity, and static electricity. But when it’s brought up in class, students are often just handed the equations. They rarely have an opportunity to discover Coulomb’s law or Newton’s law of gravitation for themselves. It’s not hard to understand why. A quantitative demonstration of Coulomb’s law can be difficult. The forces are smaller than many force sensors can measure and static electricity tends to be finicky. In addition, off-the-shelf units are expensive or difficult to use. As a result, many instructors skip this lab in favor of qualitative demonstrations or simulations. Adolf Cortel sought to remedy this by designing a straightforward experiment for measuring Coulomb’s law using charged metalized-glass spheres (Christmas ornaments) and an electronic balance. Building on Cortel’s design, we’ve made a series of video-based experiments that students can use to discover the relationships that unde...

Improvement in the ability to target underlying drivers and vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the development of molecularly annotated pre-clinical models reflective of clinical responses.We generated patient-derived xenografts (PDXs) from consecutive, chemotherapy-naïve, human HG-SOC by transplanting fresh human HG-SOC fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID IL2Rγ(null) recipient mice, completed molecular annotation and assessed platinum sensitivity.The success rate of xenografting was 83%. Of ten HG-SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three for BRCA2, and in two, BRCA1 was methylated. In vivo cisplatin response, determined as platinum sensitive (progression-free interval ≥ 100 d, n = 4), resistant (progression-free interval100 d, n = 3) or refractory (n = 3), was largely consistent with patient outcome. Three of four platinum sensitive HG-SOC PDXs contained DNA repair gene mutations, and the fourth was methylated for BRCA1. In contrast, all three platinum refractory PDXs overexpressed dominant oncogenes (CCNE1, LIN28B and/or BCL2).Because PDX platinum response reflected clinical outcome, these annotated PDXs will provide a unique model system for preclinical testing of novel therapies for HG-SOC.

Background: Treatment options for women with ovarian cancer remain very limited and acquired resistance to current therapies is very common. Altered DNA repair capability in epithelial ovarian cancer (EOC) may underlie response to both standard therapy and novel treatments, such as PARP inhibitors. Molecular sub-classification of high-grade serous ovarian cancer (HG-SOC) may uncover potential drug targets and possible mechanisms of drug resistance. Understanding the contribution of DNA repair and other driver mutations to drug response and resistance requires the development of molecularly annotated preclinical models reflective of the clinic. Methods: A patient derived xenograft (PDX) cohort has been generated from consecutive, chemotherapy-naïve human HG-SOC and stratified according to in vivo response to standard chemotherapy, DNA repair capability and molecular characteristics, including next generation sequencing by Foundation Medicine. Resistance to therapy is driven by re-treating relapsed PDX in vivo providing invaluable “paired samples” (pre and post drug treatment), which are difficult to obtain from patients, to allow clonal evolution analysis of mechanisms of drug response and resistance. Results: The xenograft success rate was 83%. Of ten HG-SOC PDX, all exhibited mutations in TP53, five in BRCA1/2 (two of which were germline) and two were methylated for BRCA1. In vivo cisplatin response, determined as platinum sensitive (progression-free interval (PFI) ≥100 d, n=4), platinum resistant (PFI Conclusion: PDX with histologic, molecular and therapeutic annotation, as well as clinical outcome data allow interrogation of molecular aberrations and drug resistance in vivo. This will inform targeting of novel therapies and the design of clinical trials for women. Citation Format: Monique D. Topp, Lynne Hartley, Michele Cook, Valerie Heong, Emma Boehm, Lauren McShane, Jan Pyman, Orla McNally, Sumi Ananda, Maria I. Harell, Dariush Etemadmoghadam, Laura Galletta, Kathryn Alsop, Gillian Mitchell, Stephen B. Fox, Jeff B. Kerr, Karla J. Hutt, Scott H. Kaufmann, Australian Ovarian Cancer Study (AOCS), Elizabeth M. Swisher, David D. Bowtell, Matthew M. Wakefield, Clare L. Scott. Using molecularly characterized patient-derived models to delineate underlying drivers and vulnerabilities of epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 38. doi:10.1158/1538-7445.CANSUSC14-38