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PURPOSE: Clinical research has shown unique tumor behavioral characteristics of BRCA-associated protein-1- (BAP1-) and fibroblast growth factor receptor (FGFR)-mutated intrahepatic cholangiocarcinomas (CCAs), with BAP1-mutated tumors demonstrating more aggressive forms of disease and FGFR-altered CCAs showing more indolent behavior. We performed a retrospective case-control study to evaluate for unique imaging features associated with BAP1 and FGFR genomic markers in intrahepatic CCA (iCCA). METHODS: Multiple imaging features of iCCA at first staging were analyzed by 2 abdominal radiologists blinded to genomic data. Growth and development of metastases at available follow-up imaging were also recorded, as were basic clinical cohort data. Types of iCCA analyzed included those with BAP1, FGFR, or both alterations, as well as cases with low mutational burden or mutations with low clinical impact, which served as a control or "wild-type" group. There were 18 cases in the FGFR group, 10 with BAP1 mutations, and 31 wild types (controls). RESULTS: Cases with BAP1 mutations showed significantly larger growth at first year of follow-up (P = 0.03) and more frequent tumor-associated biliary ductal dilatation (P = 0.04) compared with controls. FGFR-altered cases showed more infiltrative margins compared with controls (P = 0.047) and demonstrated less enhancement between arterial to portal venous phases (P = 0.02). BAP1 and FGFR groups had more cases with stage IV disease at presentation than controls (P = 0.025, P = 0.006). CONCLUSION: Compared with wild-type iCCAs, FGFR-mutated tumors often demonstrate infiltrative margins, and BAP1 tumors show increased biliary ductal dilatation at presentation. BAP1-mutated cases had significantly larger growth at first-year restaging.

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BACKGROUND: In patients undergoing resection of intrahepatic cholangiocarcinoma (ICC), hypervascularity during the arterial phase of contrast-enhanced computed tomography (CT) is associated with better prognosis than hypovascularity. However, the prognostic implications of arterial enhancement pattern in patients with unresectable ICC are unknown. We assessed the prognostic implications of arterial enhancement pattern in patients with resectable and unresectable ICC. METHODS: Consecutive patients who underwent surgery or gemcitabine-plus-cisplatin chemotherapy for ICC during 2003-2015 and CT with dynamic enhancement for diagnosis were included. After review by 2 radiologists, tumors were categorized according to the percentage of the tumor exhibiting arterial enhancement as hypervascular (>50% of tumor exhibiting enhancement), peripherally enhancing (10%-50%), and hypovascular (<10%). In each cohort (surgical and medical), overall survival (OS) curves were generated using the Kaplan-Meier method, and differences between curves were evaluated with Cox analysis. RESULTS: The study included 56 patients treated surgically and 89 patients with unresectable ICC. Mean (standard deviation) tumor density in the hypervascular, peripherally enhancing, and hypovascular groups was 119.3 (45.2) Hounsfield units (HU), 72.1 (15.9) HU, and 59.9 (14.4) HU, respectively, in the surgical cohort and 93.6 (17.5) HU, 66.6 (16.2) HU, and 48.7 (14.3) HU, respectively, in the medical cohort. In both cohorts, the 5-year OS rate was significantly higher in the hypervascular group than in the hypovascular group (surgical, 67.6% vs 22.5%, P = .038; medical, 15.4% vs 0%, P = .030). In both cohorts, a Cox proportional hazards model analysis showed that hypervascularity was significantly associated with better OS. CONCLUSION: Hypervascularity during the arterial CT phase is a prognostic biomarker in patients undergoing ICC resection and patients with unresectable ICC.

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Frente a la pandemia del CoVID-19, resulta fundamental establecer estrategias manteniendo distanciamiento social, que permitan educar a profesionales de la salud sobre aspectos relacionados con SARS-CoV-2. La Sociedad Chilena de Neumología Pediátrica creó un E-learnig de contingencia de acceso libre. OBJETIVO: Describir las características del curso online "Desafíos de la pandemia CoVID-19 en Pediatría", y evaluar el grado de satisfacción de quienes lo cursaron. Estudio transversal. Todos los inscritos en el curso, entre mayo 2020 y julio 2020. Se grabaron 12 clases dictadas por especialistas con representación académica de Chile. Se realizó una prueba final y una encuesta de satisfacción, con puntaje de 1 a 7. Se realizó análisis descriptivo e inferencial, evaluando asociación entre clasificación final del curso, profesión y zona geográfica de los participantes con test de Kruskal Wallis, significancia estadística p<0,05. Aprobado por comité ética. Participaron 2541 alumnos, 73% mujeres. Mediana de edad 32,7 años. 90,7% de Chile, de estos 63,2% de regiones. De procedencia extranjera destacó Bolivia (2,9%) y Ecuador (2,5%). De los que realizaron la prueba, el 98,6% aprobó. Existió diferencia entre notas según profesión, Médicos-Kinesiólogos(p=0.025) y Médicos-Enfermeros(p=0.002); y según procedencia, Región Metropolitana (RM)-Otras regiones (p=0.041), RM-Internacional(p<0,001) y Otras regiones-Internacional(p<0,001). La evaluación de contenidos ponderó 6,6 y la accesibilidad 6,8. El 98% contestó que el curso cumplió sus expectativas. Concluimos que se inscribió un gran número de alumnos de Chile y Latinoamérica. Más del 98% aprobó la prueba final y refirió un alto nivel de satisfacción. Sugerimos emplear estrategias similares en situaciones de catástrofes sanitarias.

In the face of the CoVID-19 pandemic, it is essential to establish strategies, maintaining social distancing, that allow educating health professionals on aspects related to SARS-CoV-2. The Chilean Society of Pediatric Pulmonology created a free access contingency E-learning. OBJECTIVE: To describe the characteristics of the online course "Challenges of the CoVID-19 pandemic in Pediatrics", and to evaluate the grade of satisfaction of those who attended it.Transversal study. All those enrolled in the course, between May 2020 and July 2020. 12 classes taught by specialists with academic representation from Chile were recorded. A final test and a satisfaction survey were carried out, with a score from 1 to 7. A descriptive and inferential analysis was implemented, evaluating the association between the final classification of the course, profession and geographical area of the participants with the Kruskal Wallis test, statistical significance p< 0.05. Approved by ethics committee. 2541 students participated, 73% women. Median age 32.7 years. 90.7% from Chile, of these 63.2% from regions. Of foreign origin, Bolivia (2.9%) and Ecuador (2.5%) stand out. Of those who took the test, 98.6% were successful. There was a difference between grades according to profession, Physicians-Kinesiologists(p=0.025) and Physicians-Nurses(p=0.002); and according to origin, Metropolitan Region (RM)-Other regions (p=0.041), RM-International (p<0.001) and Other regions-International (p<0.001). The content evaluation pondered 6.6 and accessibility 6.8. 98% responded that the course met their expectations. CONCLUSION: A large number of students from Chile and Latin America were enrolled. More than 98% passed the final test and reported a high level of satisfaction. We suggest using similar strategies in situations of health catastrophes.

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Radiologists routinely evaluate for tumor thrombus in the portal and hepatic veins in patients with hepatocellular carcinoma and in the renal vein and inferior vena cava in patients with renal cell carcinoma. However, tumor thrombus occurs in association with numerous other tumor types, e.g. colorectal carcinoma and pancreatic neuroendocrine tumor. Furthermore tumor thrombi are not limited to the primary tumor but also seen with local recurrence and metastatic disease. While less recognized, these thrombi nevertheless affect patterns of recurrence and prognosis. Their detection is critical for accurate local staging and early detection of local recurrence and metastatic disease. The purpose of this pictorial review is to draw the attention of radiologists to the less familiar manifestations of tumor thrombus, review the imaging findings and illustrate the clinical significance of these thrombi.

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PURPOSE: To analyze CT signs of bowel ischemia in patients with surgical bowel obstruction, and thereby improve CT diagnosis in this common clinical scenario. Surgical and histopathological findings were used as the reference standard. METHODS: We retrospectively analyzed CT findings in patients brought to surgery for bowel obstruction over 13 years. Etiology of obstruction (adhesion, hernia, etc.) was recorded. Specific CT features of acute mesenteric ischemia (AMI) were analyzed, including bowel wall thickening, mucosal hypoenhancement, and others. RESULTS: 173 cases were eligible for analysis. 21% of cases were positive for bowel ischemia. Volvulus, internal hernia, and closed-loop obstructions showed ischemia rates of 60%, 43%, and 43%; ischemia rate in obstruction from simple adhesion was 21%. Patients with bowel obstruction related to malignancy were never ischemic. Sensitivities and specificities for CT features predicting ischemia were calculated, with wall thickening, hypoenhancement, and pneumatosis showing high specificity for ischemia (86%-100%). CONCLUSION: Wall thickening, hypoenhancement, and pneumatosis are highly specific CT signs of ischemia in the setting of obstruction. None of the evaluated CT signs were found to be highly sensitive. Overall frequency of ischemia in surgical bowel obstruction is 21%, and 2-3 times that for complex obstructions (volvulus, closed loop, etc.). Obstructions related to malignancy virtually never become ischemic.

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Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites. Over time, the accumulation of mutations in microsatellites and elsewhere in the genome can affect the production of important cellular proteins, spurring tumorigenesis. Universal testing of colorectal tumors for microsatellite instability (MSI) is now recommended to (a) prevent cases of Lynch syndrome being missed owing to the use of clinical criteria alone, (b) reduce morbidity and mortality among the relatives of affected individuals, and (c) guide management decisions. Organ-specific cancer risks and associated screening paradigms vary according to the sex of the affected individual and the type of germline DNA alteration causing the MSI. Furthermore, Lynch syndrome-associated cancers have different pathologic, radiologic, and clinical features compared with their sporadic counterparts. Most notably, Lynch syndrome-associated tumors tend to be more indolent than non-Lynch syndrome-associated neoplasms and thus may respond differently to traditional chemotherapy regimens. The high MSI in cases of colorectal cancer reflects a difference in the biologic features of the tumor, possibly with a unique susceptibility to immunotherapy. ©RSNA, 2018.

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Pancreatic cancer is a highly lethal disease with a dismal 5-year prognosis. Knowledge of its genetics may help in identifying new methods for patient screening, and cancer treatment. In this review, we will describe the most common mutations responsible for the genesis of pancreatic cancer and their impact on screening, patterns of disease progression, and therapy.

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PURPOSE: To determine the clinical relevance of incidentally-found hypervascular micronodules (IHM) on cone-beam computed tomography angiography (CBCTA) in patients with liver metastasis undergoing transarterial (chemo)embolization (TACE/TAE). MATERIAL AND METHODS: This was a HIPAA-compliant institutional review board-approved single-institution retrospective review of 95 non-cirrhotic patients (52 men; mean age, 60 years) who underwent CBCTA prior to (chemo)embolic delivery. IHM were defined by the presence of innumerable subcentimetre hepatic parenchymal hypevascular foci not detected on pre-TACE/TAE contrast-enhanced cross-sectional imaging. Multivariate analysis was performed to compare time to tumour progression (TTP) between patients with and without IHM. RESULTS: IHM were present in 21 (22%) patients. Patients with IHM had a significantly shorter intrahepatic TTP determined by a higher frequency of developing new liver metastasis (hazard ratio [HR]: 1.99; 95% confidence interval [CI] 1.08-3.67, P= 0.02). Patients with IHM trended towards a shorter TTP of the tumour(s) treated with TACE/TAE (HR: 1.72; 95% CI: 0.98-3.01, P= 0.056). Extrahepatic TTP was not significantly different between the two cohorts (P= 0.27). CONCLUSION: Patients with IHM on CBCTA have worse prognosis due to a significantly higher risk of developing new hepatic tumours. Further work is needed to elucidate its underlying mechanisms of pathogenesis. KEY POINTS: • 21% of liver metastasis patients undergoing TACE/TAE have IHM on CBTA. • IHM are associated with a high risk of developing new hepatic tumours. • IHA are also associated with a trend toward poorer response to TACE/TAE.

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The field of cancer genomics is rapidly evolving and has led to the development of new therapies. Knowledge of commonly involved cellular pathways and genetic mutations is now essential for radiologists reading oncology cases. Radiogenomics is an emerging area of research that seeks to correlate imaging features with cancer genotypes. Such knowledge may extend the utility of multiparametric imaging to yield information regarding cancer prognosis and likelihood of therapeutic response. To date, only a handful of radiogenomics studies have been performed to evaluate solid tumors of the body, and there is much to explore. Before doing so, however, it behooves us to have adequate background knowledge of clinical cancer genomics to design meaningful radiogenomics projects and explore imaging phenotypes. Herein, an up-to-date, detailed overview is provided of well-known and common mutations of solid body tumors (such as human epithelial growth factor receptor 2, breast cancer susceptibility protein), newer genomic alterations with potential for clinical relevance, and a discussion of known related imaging findings, including existing radiogenomics data and other radiologic patterns of disease. © RSNA, 2017 Online supplemental material is available for this article.

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PURPOSE: We report updated outcomes of single- versus multifraction stereotactic body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma. METHODS AND MATERIALS: We included 167 patients with unresectable pancreatic adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of patients (87.5%) received chemotherapy. RESULTS: Median follow-up was 7.9 months (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local recurrence for patients treated with single-fraction SBRT were 5.3% (95% confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%), respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI, 0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from diagnosis for all patients was 13.6 months (95% CI, 12.2-15.0 months). The 6- and 12- month survival rates from SBRT for the single-fraction group were 67.0% (95% CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6- and 12- month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%) and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR or survival rates between the single- and multifraction groups. The 6- and 12-month cumulative incidence rates of gastrointestinal toxicity grade ≥3 were 8.1% (95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single-fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction group. There were significantly fewer instances of toxicity grade ≥2 with multifraction SBRT (P=.005). Local recurrence and toxicity grade ≥2 were independent predictors of worse survival. CONCLUSIONS: Multifraction SBRT for pancreatic cancer significantly reduces gastrointestinal toxicity without compromising local control.

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BACKGROUND: T-wave alternans (TWA) is a promising electrocardiogram (ECG) predictor of sudden cardiac arrest, yet needs specialized recordings for conventional spectral analysis. Modified moving average (MMA) analysis is a new approach that can measure TWA from routine ECGs, thus widening its applicability. However, MMA-TWA has not been calibrated against spectral TWA nor outcome in high risk patients. We hypothesized that spectral and MMA-TWA would both predict arrhythmia-free survival on long-term prospective follow-up. METHODS AND RESULTS: In 41 patients with left ventricular systolic dysfunction (ejection fraction 31 +/- 13%), we studied TWA simultaneously using spectral and MMA during pacing (< 110 beats/min). MMA amplified TWA over spectral analyses (13.0 +/- 8.28 microV vs 1.96 +/- 5.15 microV, P < 0.001). On 542 +/- 311 days' follow-up, from clinic visits, telephonic interviews, and device interrogations, there were 11 deaths or sustained ventricular arrhythmias ('events'). Positive spectral TWA (>or=1.9 microV) identified patients with from those without events (P = 0.02). Receiver-operating characteristics for MMA-TWA showed that the cutpoint >or= 10.75 microV was optimal for the combined endpoint. Kaplan-Meier analysis using this MMA-TWA cutpoint trended to predict events (P = 0.06), while MMA combined with spectral TWA identified events (P = 0.01). CONCLUSIONS: MMA amplifies TWA compared to traditional spectral analyses, but both likely reflect similar pathophysiology. Validation in larger populations will enable MMA-TWA to be widely applied to stratify risk for sudden cardiac arrest.

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Naloxone benzoylhydrazone (NalBzoH) is a ligand used to study opioid receptors. It has been suggested to act at a novel kappa3 receptor but also appears to bind to classical opioid receptors, and possibly the ORL1 receptor. We have used opioid receptor triple knockout mice, deficient in genes coding for the mu, delta and kappa-receptor, to characterise the relative contributions of opioid and ORL1 activity to the binding of this ligand, by carrying out receptor autoradiography with [3H]NalBzoH. As competing ligands we have used diprenorphine and nociceptin at 1 microM, alone or in combination, to determine the contribution of opioid and ORL1 receptor binding. At 4 nM [3H]NalBzoH showed labelling in wild-type brains indicative of broad spectrum classical opioid receptor binding. In the triple knockout brains all labelling was completely absent, suggesting that at this concentration there is no binding to ORL1 sites. However at 50 nM [3H]NalBzoH showed labelling in triple knockout brains with a distribution pattern indicative of ORL1 labelling. Quantitative analysis showed that nociceptin displaced typically 30% of the residual labelling in knockout brains whilst diprenorphine had relatively little effect. The data show that at 50 nM NalBzoH no binding was detected other than to classical opioid receptors or to ORL1 in an approximate ratio of 2:1.

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Seeds from the African legume shrub Griffonia simplicifolia contain several lectins. Among them the tetrameric lectin GS I-B(4) has strict specificity for terminal alpha Gal residues, whereas the closely related lectin GS I-A(4) can also bind to alpha GalNAc. These two lectins are commonly used as markers in histology or for research in xenotransplantation. To elucidate the basis for the fine difference in specificity, the amino acid sequences of both lectins have been determined and show 89% identity. The crystal structure of GS I-B(4), determined at 2.5-A resolution, reveals a new quaternary structure that has never been observed in other legume lectins. An unexpected loss of both Ca(2+) and Mn(2+) ions, which are necessary for carbohydrate binding in legume lectins, may be related to a particular amino acid sequence Pro-Glu-Pro in the metal binding loop. Comparison with demetallized concanavalin A reveals a different process for the loss of metal ions and for the subsequent loss of carbohydrate binding activity. The GS I-A x alpha GalNAc and GS I-B x alpha Gal complexes were constructed using homology modeling and docking approaches. The unusual presence of an aromatic amino acid at position 47 (Tyr in I-A and Trp in I-B) explains the strong preference for alpha-anomeric sugars in both isolectins. Alteration at one amino acid position, Ala(106) in I-A versus Glu(106) in I-B, is the basis for the observed specificities toward alpha GalNAc and alpha Gal.

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