Infectious and Inflammatory Sinonasal Diseases.

Rhinosinusitis is a commonly encountered disease. Imaging is not typically required in acute uncomplicated rhinosinusitis; however, it is integral in the evaluation of patients who present with prolonged or atypical symptoms or when acute intracranial complications or alternate diagnoses are suspected. Knowledge of the paranasal sinus anatomy is important to understand patterns of sinonasal opacification. Bacterial, viral, and fungal pathogens are responsible culprits and, with duration of symptoms, serve to categorize infectious sinonasal disease. Several systemic inflammatory and vasculitic processes have a predilection for the sinonasal region. Imaging, along with laboratory and histopathologic analysis, assist in arriving at these diagnoses.

Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.

Correction: Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer.

[This corrects the article DOI: 10.1371/journal.pcbi.1006840.].

Using CT texture analysis to differentiate cystic and cystic-appearing odontogenic lesions.

PURPOSE: Cystic and cystic-appearing odontogenic lesions of the jaw may appear similar on CT imaging. Accurate diagnosis is often difficult although the relationship of the lesion to the tooth root or crown may offer a clue to the etiology. The purpose of this study was to evaluate CT texture analysis as an aid in differentiating cystic and cystic-appearing odontogenic lesions of the jaw. METHODS: This was an IRB-approved retrospective study including 42 pathology-proven dentigerous cysts, 37 odontogenic keratocysts, and 19 ameloblastomas. Each lesion was manually segmented on axial CT images, and textural features were analyzed using an in-house-developed Matlab-based texture analysis program that extracted 47 texture features from each segmented volume. Statistical analysis was performed comparing all pairs of the three types of lesions. RESULTS: Pairwise analysis revealed that nine histogram features, one GLCM feature, three GLRL features, two Laws features, four GLGM features and two Chi-square features showed significant differences between dentigerous cysts and odontogenic keratocysts. Four histogram features and one Chi-square feature showed significant differences between odontogenic keratocysts and ameloblastomas. Two histogram features showed significant differences between dentigerous cysts and ameloblastomas. CONCLUSIONS: CT texture analysis may be useful as a noninvasive method to obtain additional quantitative information to differentiate cystic and cystic-appearing odontogenic lesions of the jaw.

Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer.

Drug resistance in breast cancer cell populations has been shown to arise through phenotypic transition of cancer cells to a drug-tolerant state, for example through epithelial-to-mesenchymal transition or transition to a cancer stem cell state. However, many breast tumors are a heterogeneous mixture of cell types with numerous epigenetic states in addition to stem-like and mesenchymal phenotypes, and the dynamic behavior of this heterogeneous mixture in response to drug treatment is not well-understood. Recently, we showed that plasticity between differentiation states, as identified with intracellular markers such as cytokeratins, is linked to resistance to specific targeted therapeutics. Understanding the dynamics of differentiation-state transitions in this context could facilitate the development of more effective treatments for cancers that exhibit phenotypic heterogeneity and plasticity. In this work, we develop computational models of a drug-treated, phenotypically heterogeneous triple-negative breast cancer (TNBC) cell line to elucidate the feasibility of differentiation-state transition as a mechanism for therapeutic escape in this tumor subtype. Specifically, we use modeling to predict the changes in differentiation-state transitions that underlie specific therapy-induced changes in differentiation-state marker expression that we recently observed in the HCC1143 cell line. We report several statistically significant therapy-induced changes in transition rates between basal, luminal, mesenchymal, and non-basal/non-luminal/non-mesenchymal differentiation states in HCC1143 cell populations. Moreover, we validate model predictions on cell division and cell death empirically, and we test our models on an independent data set. Overall, we demonstrate that changes in differentiation-state transition rates induced by targeted therapy can provoke distinct differentiation-state aggregations of drug-resistant cells, which may be fundamental to the design of improved therapeutic regimens for cancers with phenotypic heterogeneity.

Using CT texture analysis to differentiate between nasopharyngeal carcinoma and age-matched adenoid controls.

OBJECTIVES: To investigate the use of texture analysis to quantitatively distinguish nasopharyngeal carcinoma (NPC) from normal adenoid on CT. METHODS: In this IRB-approved, retrospective study, nasopharyngeal tissues in 13 patients with NPC and 13 control patients were manually contoured, segmented, and imported to an in-house developed texture analysis program, which extracted 41 texture features. Basic descriptive statistics were performed to evaluate for differences in texture parameters between NPC and controls. RESULTS: Statistically significant differences between NPC and controls were seen in 32 of 41 texture features. These significant differences were present in 11 of 12 histogram features, 4 of 5 gray-level co-occurrence matrix features, 7 of 11 gray-level run length features, 4 of 4 gray-level gradient matrix features, and 6 of 9 Laws features. CONCLUSION: Significant differences in many texture features were seen between NPC and normal adenoids. CT texture analysis may aid in differentiating NPC from normal adenoid tissue.

Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer.

Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity and is associated with resistance to cytotoxic and targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, is high in triple-negative and basal-like breast cancer subtypes, and that drug tolerant persister (DTP) cell populations with altered marker expression emerge during treatment with a wide range of pathway-targeted therapeutic compounds. We show that MEK and PI3K/mTOR inhibitor-driven DTP states arise through distinct cell-state transitions rather than by Darwinian selection of preexisting subpopulations, and that these transitions involve dynamic remodeling of open chromatin architecture. Increased activity of many chromatin modifier enzymes, including BRD4, is observed in DTP cells. Co-treatment with the PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevents changes to the open chromatin architecture, inhibits the acquisition of a DTP state, and results in robust cell death in vitro and xenograft regression in vivo.

Craniofacial Manifestations of Systemic Disorders: CT and MR Imaging Findings and Imaging Approach.

Many systemic diseases or conditions can affect the maxillofacial bones; however, they are often overlooked or incidentally found at routine brain or head and neck imaging performed for other reasons. Early identification of some conditions may significantly affect patient care and alter outcomes. Early recognition of nonneoplastic hematologic disorders, such as thalassemia and sickle cell disease, may help initiate earlier treatment and prevent serious complications. The management of neoplastic diseases such as lymphoma, leukemia, or Langerhans cell histiocytosis may be different if diagnosed early, and metastases to the maxillofacial bones may be the first manifestation of an otherwise occult neoplasm. Endocrinologic and metabolic disorders also may manifest with maxillofacial conditions. Earlier recognition of osteoporosis may alter treatment and prevent complications such as insufficiency fractures, and identification of acromegaly may lead to surgical treatment if there is an underlying growth hormone-producing adenoma. Bone dysplasias sometimes are associated with skull base foraminal narrowing and subsequent involvement of the cranial nerves. Inflammatory processes such as rheumatoid arthritis and sarcoidosis may affect the maxillofacial bones, skull base, and temporomandibular joints. Radiologists should be familiar with the maxillofacial computed tomographic and magnetic resonance imaging findings of common systemic disorders because these may be the first manifestations of an otherwise unrevealed systemic process with potential for serious complications. Online supplemental material is available for this article. ©RSNA, 2018.

Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial.

IMPORTANCE: For treatment of malignant pleural effusion, nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided because they may reduce pleurodesis efficacy. Smaller chest tubes may be less painful than larger tubes, but efficacy in pleurodesis has not been proven. OBJECTIVE: To assess the effect of chest tube size and analgesia (NSAIDs vs opiates) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion. DESIGN, SETTING, AND PARTICIPANTS: A 2×2 factorial phase 3 randomized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013. INTERVENTIONS: Patients undergoing thoracoscopy (n = 206; clinical decision if biopsy was required) received a 24F chest tube and were randomized to receive opiates (n = 103) vs NSAIDs (n = 103), and those not undergoing thoracoscopy (n = 114) were randomized to 1 of 4 groups (24F chest tube and opioids [n = 28]; 24F chest tube and NSAIDs [n = 29]; 12F chest tube and opioids [n = 29]; or 12F chest tube and NSAIDs [n = 28]). MAIN OUTCOMES AND MEASURES: Pain while chest tube was in place (0- to 100-mm visual analog scale [VAS] 4 times/d; superiority comparison) and pleurodesis efficacy at 3 months (failure defined as need for further pleural intervention; noninferiority comparison; margin, 15%). RESULTS: Pain scores in the opiate group (n = 150) vs the NSAID group (n = 144) were not significantly different (mean VAS score, 23.8 mm vs 22.1 mm; adjusted difference, -1.5 mm; 95% CI, -5.0 to 2.0 mm; P = .40), but the NSAID group required more rescue analgesia (26.3% vs 38.1%; rate ratio, 2.1; 95% CI, 1.3-3.4; P = .003). Pleurodesis failure occurred in 30 patients (20%) in the opiate group and 33 (23%) in the NSAID group, meeting criteria for noninferiority (difference, -3%; 1-sided 95% CI, -10% to ∞; P = .004 for noninferiority). Pain scores were lower among patients in the 12F chest tube group (n = 54) vs the 24F group (n = 56) (mean VAS score, 22.0 mm vs 26.8 mm; adjusted difference, -6.0 mm; 95% CI, -11.7 to -0.2 mm; P = .04) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure (30% vs 24%), failing to meet noninferiority criteria (difference, -6%; 1-sided 95% CI, -20% to ∞; P = .14 for noninferiority). Complications during chest tube insertion occurred more commonly with 12F tubes (14% vs 24%; odds ratio, 1.91; P = .20). CONCLUSIONS AND RELEVANCE: Use of NSAIDs vs opiates resulted in no significant difference in pain scores but was associated with more rescue medication. NSAID use resulted in noninferior rates of pleurodesis efficacy at 3 months. Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinically modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN33288337.

Periapical lucency around the tooth: radiologic evaluation and differential diagnosis.

Periapical lucencies are often seen incidentally at head and neck imaging studies performed for indications not related to the teeth. These lesions are, however, occasionally manifestations of diseases that have a wide range of effects and may at times represent the source of symptoms that prompted the study. The vast majority of periapical lucencies are the result of apical periodontal or pulpal disease. If found in an advanced state or left untreated, disease related to the tooth may spread to adjacent tissues, including the sinuses, orbits, deep fascial spaces of the neck, and intracranial structures, and result in a significant increase in patient morbidity and mortality. Although the majority of periapical lucencies seen on radiographs and computed tomographic images occur secondary to apical periodontal or pulpal disease, not all lucencies near the tooth root are due to infection. Lucency near the tooth root may be seen in the setting of other diseases of odontogenic and non-odontogenic origin, including neoplasms. Although imaging findings for these lesions can include periapical lucent components, awareness of the varied secondary imaging features can aid the radiologist in developing an accurate differential diagnosis. Familiarity with the imaging features and differential diagnoses of diseases or conditions that cause lucency around the tooth root results in appropriate referral and prompt diagnosis, management, and treatment, and can prevent unnecessary additional imaging or intervention. In addition, early recognition and appropriate treatment of infectious processes will result in improved clinical outcomes and a decrease in morbidity and mortality.

IgG4-related disease of the head and neck: CT and MR imaging manifestations.

Immunoglobulin G4 (IgG4)-related disease is a recently established systemic disease that commonly involves the head and neck, including the salivary glands, lacrimal glands, orbits, thyroid gland, lymph nodes, sinonasal cavities, pituitary gland, and larynx. Although the definitive diagnosis of IgG4-related disease requires histopathologic analysis, elevated serum IgG4 levels are helpful in making the diagnosis. Because of the proposed clinical diagnostic criteria for this disease, cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance (MR) imaging play an important diagnostic role. CT and MR imaging findings of IgG4-related disease are usually nonspecific. At CT, involved organs may demonstrate enlargement or decreased attenuation; at T2-weighted MR imaging, they may have relatively low signal intensity owing to their increased cellularity and amount of fibrosis. Some pathologic entities involving the head and neck are now considered to be part of the IgG4-related disease spectrum, including idiopathic orbital inflammatory syndrome (inflammatory pseudotumor), orbital lymphoid hyperplasia, Mikulicz disease, Küttner tumor, Hashimoto thyroiditis, Riedel thyroiditis, and pituitary hypophysitis. Because involvement of multiple sites is common in IgG4-related disease, radiologists should be familiar with manifestations of this systemic process outside the head and neck, in organs such as the pancreas, bile ducts, gallbladder, kidneys, retroperitoneum, mesentery, lungs, gastrointestinal tract, and blood vessels. Moreover, IgG4-related disease usually demonstrates a dramatic response to corticosteroid therapy, and radiologists should be familiar with its clinical and imaging manifestations to avoid a delay in diagnosis or unnecessary invasive interventions.