De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features.

Selenophosphate synthetase (SEPHS) plays an essential role in selenium metabolism. Two mammalian SEPHS paralogues, SEPHS1 and SEPHS2, share high sequence identity and structural homology with SEPHS. Here, we report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo. Structural modeling and biochemical assays were used to understand the effect of these variants on SEPHS1 function. We found that a variant at residue Trp352 results in local structural changes of the C-terminal region of SEPHS1 that decrease the overall thermal stability of the enzyme. In contrast, variants of a solvent-exposed residue Arg371 do not impact enzyme stability and folding but could modulate direct protein-protein interactions of SEPSH1 with cellular factors in promoting cell proliferation and development. In neuronal SH-SY5Y cells, we assessed the impact of SEPHS1 variants on cell proliferation and ROS production and investigated the mRNA expression levels of genes encoding stress-related selenoproteins. Our findings provided evidence that the identified SEPHS1 variants enhance cell proliferation by modulating ROS homeostasis. Our study supports the hypothesis that SEPHS1 plays a critical role during human development and provides a basis for further investigation into the molecular mechanisms employed by SEPHS1. Furthermore, our data suggest that variants in SEPHS1 are associated with a neurodevelopmental disorder.

Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter.

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 Å resolution (extending to 2.2 Å at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 Å resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the 'elevator-with-an-operator' mechanism of TRAP transporters.

Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant.

Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural understanding of IL-11 signalling and mechanistic insights into current inhibitors are lacking. Here we present cryo-EM and crystal structures of the human IL-11 signalling complex, including the complex containing the complete extracellular domains of the shared IL-6 family ß-receptor, gp130. We show that complex formation requires conformational reorganisation of IL-11 and that the membrane-proximal domains of gp130 are dynamic. We demonstrate that the cytokine mutant, IL-11 Mutein, competitively inhibits signalling in human cell lines. Structural shifts in IL-11 Mutein underlie inhibition by altering cytokine binding interactions at all three receptor-engaging sites and abrogating the final gp130 binding step. Our results reveal the structural basis of IL-11 signalling, define the molecular mechanisms of an inhibitor, and advance understanding of gp130-containing receptor complexes, with potential applications in therapeutic development.

Bone Cement Waste in Total Knee Arthroplasty: A Preliminary Study of Scope and Cost.

Background: Medical waste is both costly and detrimental to the environment, and operating room waste represents a substantial portion of this. To the authors' knowledge, bone cement waste in total knee arthroplasty (TKA) has not previously been studied. The vast majority of TKA are cemented, and the volume of TKA is forecast to increase. Given this, we studied the waste resulting from the routine use of 2 40-gram bags of polymethyl methacrylate (PMMA) powder during cementing in primary TKA. Methods: We first studied the yield of commercially available plain and gentamicin medium-viscosity bone cement powder and calculated the cost/gram of product. We then collected the PMMA remaining after primary TKA to determine the average amount of waste, its cost, and possible correlations with patient and implant metrics that could improve efficiency and reduce waste of PMMA. Results: Overall, PMMA waste averaged 59% per TKA, at a median cost of $129 per case. Cost of waste was greater when gentamicin cement was used, as its cost was 2.5X that of plain cement. Implant sizes and surface area ranges were identified that could reliably allow the use of a single 40-gram package of powder, potentially reducing PMMA waste. Conclusions: While it is acknowledged that zero-waste cementing is not practical, any reduction in waste that does not compromise either the flow of surgery or the adequacy of fixation would be beneficial. Reevaluation of PMMA techniques could reduce waste, resulting in both cost savings and improved sustainability in arthroplasty.

Post-pneumonectomy syndrome: a systematic review of the current evidence and treatment options.

OBJECTIVES: Post-pneumonectomy syndrome (PPS) is rare and predominantly characterised by dynamic airway obstruction due to mediastinal rotation at any time point following pneumonectomy. The objective of this systematic review was to identify the optimal treatment strategy for PPS based on subjective symptomatic relief, objective radiological imaging, and treatment durability. METHODS: A systematic review was performed up to and including February 2022 based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines. All studies that presented the management of symptomatic patients > 16 years of age with radiologically confirmed PPS were included. The primary outcome was the identification of the optimal treatment strategy and the secondary outcome was durability of the treatment. The Oxford Centre for Evidence Based Medicine level was assigned to each study. RESULTS: A total of 330 papers were identified and reviewed; 41 studies met the inclusion criteria. Data including patient demographics, indication for initial pneumonectomy, presenting symptoms, management approach, outcomes, and follow-up were assessed and analysed. Management approaches were divided into three categories: (a) mediastinal repositioning using implant prostheses; (b) endobronchial stenting; (c) other corrective procedures. One hundred and four patients were identified in total and of those, 87 underwent mediastinal repositioning with insertion of a prosthetic implant. Complications included over- or under-filling of the prosthesis (8.5%) and implant leakage (8.9%). CONCLUSION: Management of PPS using a prosthetic implant to reposition the mediastinum is the treatment of choice. Key adjuncts to optimise surgical approach and minimise complications include pre-operative CT volumetric analysis to guide implant size and intra-operative transoesophageal echocardiography to guide mediastinal repositioning.

Rescue Transesophageal Echocardiography: A Narrative Review of Current Knowledge and Practice.

Perioperative transesophageal echocardiography (TEE) has been part of clinical activity for more than 40 years. During this period, TEE has evolved in terms of technology and clinical applications beyond the initial fields of cardiology and cardiac surgery. The benefits of TEE in the diagnosis and management of acute hemodynamic and respiratory collapse have been recognized in noncardiac surgery and by other specialties too. This natural progress led to the development of rescue TEE, a relatively recent clinical application that extends the use of TEE and makes it accessible to a large group of clinicians and patients requiring acute care. In this review, the authors appraise the current clinical applications and evidence base around this topic. The authors provide a thorough review of the various image acquisition protocols, clinical benefits, and compare it with the more frequently used transthoracic echocardiography. Furthermore, the authors have reviewed the current training and credentialing pathways. Overall, rescue TEE is a highly attractive and useful point-of-care examination, but the current evidence base is limited and the technical protocols, training, and credentialing processes are not standardized. There is a need for adequate guidelines and high-quality research to support its application as a bedside rescue tool.

S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer.

Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT, and mesenchymal states, each of which is associated with cancer progression, invasive capabilities, and ultimately, metastasis. We used a lineage-traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that underwent partial EMT and complete EMT. Using an unbiased proteomics approach, we found that organoid morphology predicts the EMT state, and the solid organoids are associated with a partial EMT signature. We also observed that exogenous TGFß1 induces solid organoid morphology that is associated with changes in the S100 family, complete EMT, and the formation of high-grade tumors. S100A4 may be a useful biomarker for predicting EMT state, disease progression, and outcome in patients with pancreatic cancer.

The utility of a symptom model to predict the risk of oesophageal cancer.

OBJECTIVE: To assess whether extra-oesophageal symptoms are predictive of oesophageal malignancy. METHODS: A prospective, single-centre cross-sectional questionnaire study at a tertiary referral unit for oesophageal cancer using the Comprehensive Reflux Symptoms Scale (CReSS) questionnaire tool. Respondents with oesophageal malignancy were compared with historical cohorts undergoing airway examination or upper gastrointestinal endoscopy and found to have benign diagnoses. We developed a model for predicting oesophageal cancer using linear discriminant analysis and logistic regression, assessed by Monte Carlo cross validation. RESULTS: Respondents with oesophageal malignancy (n = 146; mean age 70.5; male: female, 71:29) were compared with those undergoing airway examination (n = 177) and upper gastrointestinal endoscopy (n = 351), found to have benign diagnoses. No single questionnaire item, or group of co-varying items (factors), reliably discriminated oesophageal cancer from other diagnoses. Individual items which suggested higher risk of oesophageal malignancy included dysphagia (area under the curve (AUC) 0.68), low appetite (AUC 0.66), and early satiety (AUC 0.58). Conversely, throat pain (AUC 0.38), bloating (AUC 0.38) and heartburn (AUC 0.37) were inversely related to cancer risk. A forward stepwise regression analysis including a subset of 12 CReSS questionnaire items together with age and sex derived a model predictive of oesophageal malignancy in this cohort (AUC 0.89). CONCLUSION: We demonstrate a model comprised of 12 questionnaire items and 2 demographic parameters as a potential predictive tool for oesophageal malignancy diagnosis in this study population. Translating this model for predicting oesophageal malignancy in the general population is a valuable topic for future research.

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5'-monophosphate-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5'-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite Plasmodium falciparum, namely tyrosine RS (PfYRS). ML901 exerts whole-life-cycle-killing activity with low nanomolar potency and single-dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction hijacking by ML901.

Exposure to bile and gastric juice can impact the aerodigestive microbiome in people with cystic fibrosis.

Studies of microbiota reveal inter-relationships between the microbiomes of the gut and lungs. This relationship may influence the progression of lung disease, particularly in patients with cystic fibrosis (CF), who often experience extraoesophageal reflux (EOR). Despite identifying this relationship, it is not well characterised. Our hypothesis is that the gastric and lung microbiomes in CF are related, with the potential for aerodigestive pathophysiology. We evaluated gastric and sputum bacterial communities by culture and 16S rRNA gene sequencing in 13 CF patients. Impacts of varying levels of bile acids, pepsin and pH on patient isolates of Pseudomonas aeruginosa (Pa) were evaluated. Clonally related strains of Pa and NTM were identified in gastric and sputum samples from patients with symptoms of EOR. Bacterial diversity was more pronounced in sputa compared to gastric juice. Gastric and lung bile and pepsin levels were associated with Pa biofilm formation. Analysis of the aerodigestive microbiomes of CF patients with negative sputa indicates that the gut can be a reservoir of Pa and NTM. This combined with the CF patient's symptoms of reflux and potential aspiration, highlights the possibility of communication between microorganisms of the gut and the lungs. This phenomenon merits further research.

Molecular Basis of Functional Effects of Phosphorylation of the C-Terminal Domain of the Rabies Virus P Protein.

The rabies virus (RABV) phosphoprotein (P protein) is expressed as several isoforms, which differ in nucleocytoplasmic localization and microtubule (MT) association, mediated by several sequences, including nuclear localization (NLS) and export (NES) sequences. This appears to underpin a functional diversity enabling multiple functions in viral replication and modulation of host biology. Mechanisms regulating trafficking are poorly defined, but phosphorylation by protein kinase C (PKC) in the P protein C-terminal domain (PCTD) regulates nuclear trafficking, mediated by PCTD-localized NLS/NES sequences, indicating that phosphorylation contributes to functional diversity. The molecular mechanism underlying the effects of PKC, and potential roles in regulating other host-cell interactions are unresolved. Here, we assess effects of phosphorylation on the P3 isoform, which differs from longer isoforms through an ability to localize to the nucleus and associate with MTs, which are associated with antagonism of interferon (IFN) signaling. We find that phosphomimetic mutation of the PKC site S210 inhibits nuclear accumulation and MT association/bundling. Structural analysis indicated that phosphomimetic mutation induces no significant structural change to the NLS/NES but results in the side chain of N226 switching its interactions from E228, within the NES, to E210. Intriguingly, N226 is the sole substituted residue between the PCTD of the pathogenic IFN-resistant RABV strain Nishigahara and a derivative attenuated IFN-sensitive strain Ni-CE, inhibiting P3 nuclear localization and MT association. Thus, S210 phosphorylation appears to impact on N226/E228 to regulate P protein localization, with N226 mutation in Ni-CE mimicking a constitutively phosphorylated state resulting in IFN sensitivity and attenuation. IMPORTANCE Rabies virus P protein is a multifunctional protein with critical roles in replication and manipulation of host-cell processes, including subversion of immunity. This functional diversity involves interactions of several P protein isoforms with the cell nucleus and microtubules. Previous studies showed that phosphorylation of the P protein C-terminal domain (PCTD) at S210, near nuclear trafficking sequences, regulates nucleocytoplasmic localization, indicating key roles in functional diversity. The molecular mechanisms of this regulation have remained unknown. Here, we show that phosphomimetic mutation of S210 regulates nuclear localization and MT association. This regulation does not appear to result from disrupted PCTD structure, but rather from a switch of specific side chain interactions of N226. Intriguingly, N226 was previously implicated in P protein nuclear localization/MT association, immune evasion, and RABV pathogenesis, through undefined mechanisms. Our data indicate that the S210-N226 interface is a key regulator of virus-host interactions, which is significant for pathogenesis.

Image Quality Evaluation in Dual-Energy CT of the Chest, Abdomen, and Pelvis in Obese Patients With Deep Learning Image Reconstruction.

OBJECTIVE: The aim of this study was to evaluate image quality in vascular and oncologic dual-energy computed tomography (CT) imaging studies performed with a deep learning (DL)-based image reconstruction algorithm in patients with body mass index of ≥30. METHODS: Vascular and multiphase oncologic staging dual-energy CT examinations were evaluated. Two image reconstruction algorithms were applied to the dual-energy CT data sets: standard of care Adaptive Statistical Iterative Reconstruction (ASiR-V) and TrueFidelity DL image reconstruction at 2 levels (medium and high). Subjective quality criteria were independently evaluated by 4 abdominal radiologists, and interreader agreement was assessed. Signal-to-noise ratio (SNR) and contrast-to-noise ratio were compared between image reconstruction methods. RESULTS: Forty-eight patients were included in this study, and the mean patient body mass index was 39.5 (SD, 7.36). TrueFidelity-High (DL-High) and TrueFidelity-Medium (DL-Med) image reconstructions showed statistically significant higher Likert scores compared with ASiR-V across all subjective image quality criteria ( P < 0.001 for DL-High vs ASiR-V; P < 0.05 for DL-Med vs ASiR-V), and SNRs for aorta and liver were significantly higher for DL-High versus ASiR-V ( P < 0.001). Contrast-to-noise ratio for aorta and SNR for aorta and liver were significantly higher for DL-Med versus ASiR-V ( P < 0.05). CONCLUSIONS: TrueFidelity DL image reconstruction provides improved image quality compared with ASiR-V in dual-energy CTs obtained in obese patients.

A review of European guidelines for patient blood management with a particular emphasis on antifibrinolytic drug administration for cardiac surgery.

The concept of patient blood management (PBM) was introduced by the World Health Organization in 2011 and is defined as a "patient-focused, evidence-based and systematic approach for optimizing the management of patients and transfusion of blood products to ensure high quality and effective patient care". Patient blood management is a multimodal approach based on three pillars: optimization of blood mass, minimization of blood loss and optimization of patient tolerance to anaemia. Antifibrinolytics play a major role in cardiac surgery, where the risk of perioperative bleeding is high and affects a majority of patients, by effectively reducing bleeding, transfusions, re-operations, as well as their associated morbidity and mortality. They represent an essential part of the pharmacological arsenal of patient blood management. However, despite the trend towards high-level PBM practices, currently very few European countries have national PBM guidelines and these guidelines, taken as a whole, are heterogeneous in form and content. In particular, the use of antifibrinolytics in cardiac surgery is often not discussed in detail beyond general prophylactic use and any recommendations lack detail including choice of drug, dosing, and mode of administration. Thus, the implementation of PBM programs in Europe is still challenging. In 2021, the WHO published a new document highlighting the urgent need to close the gap in PBM awareness and implementation and announced their upcoming initiative to develop specific PBM implementation guidelines. This review aims first, to summarize the role played by fibrinolysis in haemostatic disorders; second, to give an overview of the current available guidelines in Europe detailing PBM implementation in cardiac surgery; and third, to analyse the place and use of antifibrinolytics in these guidelines.

Undifferentiated carcinoma with osteoclast-like giant cells: A pathologic-radiologic correlation of a rare histologic subtype of pancreatic ductal adenocarcinoma.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an exceedingly rare subtype of pancreatic ductal adenocarcinoma. Histologically, UC-OGC is characterized by three cell types namely, a neoplastic mononuclear cell component, non-neoplastic osteoclast-like giant cells, and a non-neoplastic mononuclear histiocytic component. The behavior of this tumor is unpredictable; but many patients survive many years after diagnosis. UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma due to its slower local spread, less aggressive nature, better response to surgical resection and/or chemotherapy, and fewer metastases. Due to likely differences in prognosis and significant impact on patient management, it is important to distinguish this subtype from other types of pancreatic adenocarcinoma. We report a case of a small (<1 cm) undifferentiated carcinoma with osteoclast-like giant cells of the posterior pancreatic body discovered incidentally on magnetic resonance image (MRI) scan of a middle-aged man. The radiologic and pathologic findings are presented along with a discussion of the differential diagnosis of this exceedingly rare entity.

Perioperative Management of the Fontan Patient for Cardiac and Noncardiac Surgery.

The Fontan circulation is the single-ventricle approach to surgical palliation of complex congenital heart disease wherein biventricular separation and function cannot be safely achieved. Incremental improvements in this surgical technique, along with improvements in the long-term medical management of these patients, have led to greater survival of these patients and a remarkably steady increase in the number of adults living with this unusual circulation and physiology. This has implications for healthcare providers who now have a greater chance of encountering Fontan patients during the course of their practice. This has particularly important implications for anesthesiologists because the effects of their interventions on the finely balanced Fontan circulation may be profound. The American Heart Association and American College of Cardiology recommend that, when possible, elective surgery should be performed in an adult congenital heart disease center, although this may not be feasible in the provision of true emergency care. This review article summarizes the pathophysiology pertinent to the provision of anesthesia in this complex patient group and describes important modifications to anesthetic technique and perioperative management.

Emerging roles for IL-11 in inflammatory diseases.

Interleukin-11 (IL-11) is a cytokine that has been strongly implicated in the pathogenesis of fibrotic diseases and solid malignancies. Elevated IL-11 expression is also associated with several non-malignant inflammatory diseases where its function remains less well-characterized. Here, we summarize current literature surrounding the contribution of IL-11 to the pathogenesis of autoimmune inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, diabetes and systemic sclerosis, as well as other chronic inflammatory conditions such as periodontitis, asthma, chronic obstructive pulmonary disease, psoriasis and colitis.

Multi-Site Concordance of Diffusion-Weighted Imaging Quantification for Assessing Prostate Cancer Aggressiveness.

BACKGROUND: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. PURPOSE: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms. STUDY TYPE: Prospective. POPULATION: Thirty-three patients prospectively imaged prior to prostatectomy. FIELD STRENGTH/SEQUENCE: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence. ASSESSMENT: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC). STATISTICAL TEST: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant. RESULTS: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size. DATA CONCLUSION: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome.

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) ß5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of P. falciparum compared with a human cell line and exhibit high potency against field isolates of P. falciparum and Plasmodium vivax They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity. Exemplar compounds, MPI-5 and MPI-13, show potent activity against P. falciparum infections in a SCID mouse model with an oral dosing regimen that is well tolerated. We show that MPI-5 binds more strongly to Pf20S than to human constitutive 20S (Hs20Sc). Comparison of the cryo-electron microscopy (EM) structures of Pf20S and Hs20Sc in complex with MPI-5 and Pf20S in complex with the clinically used anti-cancer agent, bortezomib, reveal differences in binding modes that help to explain the selectivity. Together, this work provides insights into the 20S proteasome in P. falciparum, underpinning the design of potent and selective antimalarial proteasome inhibitors.

Multimodality Imaging for the Staging of Pancreatic Cancer.

Imaging plays a key role in the diagnosis, staging, and follow-up of pancreatic ductal adenocarcinoma. The pancreatic protocol dual-phase multidetector computed tomography scan is the imaging modality of choice. A computed tomography scan is highly accurate for pancreatic tumor detection, assessment of resectability, and detection of metastatic disease. This article reviews key principles of the acquisition, interpretation, and reporting of pancreatic ductal adenocarcinoma imaging with computed tomography scanning and highlights potential roles for newer and supplemental imaging technologies. We discuss the importance of structured interpretation and reporting for providing the most complete and accurate assessment of tumor stage and resectability.