MGMT Methylation and Differential Survival Impact by Sex in Glioblastoma.

Introduction: Sex differences in glioblastoma (GBM) have been observed in incidence, genetic and epigenetic alterations, and immune response. These differences have extended to the methylation of the MGMT promoter, which critically impacts temozolomide resistance. However, the association between sex, MGMT methylation, and survival is poorly understood, which this study sought to evaluate. Methods: A retrospective cohort study was conducted and reported following STROBE guidelines, based on adults with newly diagnosed GBM who received their first surgical intervention at Cleveland Clinic (Ohio, USA) between 2012 and 2018. Kaplan-Meier and multivariable Cox proportional hazards models were used to analyze the association between sex and MGMT promoter methylation status on overall survival (OS). MGMT was defined as methylated if the mean of CpG 1-5 ≥ 12. Propensity score matching was performed on a subset of patients to evaluate the effect of individual CpG site methylation. Results: A total of 464 patients had documented MGMT methylation status with a mean age of 63.4 (range 19-93) years. A total of 170 (36.6%) were female, and 133 (28.7%) received gross total resection as a first intervention. A total of 42.5% were MGMT methylated, with females more often having MGMT methylation than males (52.1% vs. 37.4%, p = 0.004). In univariable analysis, OS was significantly longer for MGMT promoter methylated than un-methylated groups for females (2 yr: 36.8% vs. 11.1%; median: 18.7 vs. 9.5 months; p = 0.001) but not for males (2 yr: 24.3% vs. 12.2%; median: 12.4 vs. 11.3 months; p = 0.22, p for MGMT-sex interaction = 0.02). In multivariable analysis, MGMT un-methylated versus methylated promoter females (2.07; 95% CI, 1.45-2.95; p < 0.0001) and males (1.51; 95% CI, 1.14-2.00; p = 0.004) had worse OS. Within the MGMT promoter methylated group, males had significantly worse OS than females (1.42; 95% CI: 1.01-1.99; p = 0.04). Amongst patients with data on MGMT CpG promoter site methylation values (n = 304), the median (IQR) of CpG mean methylation was 3.0% (2.0, 30.5). Females had greater mean CpG methylation than males (11.0 vs. 3.0, p < 0.002) and higher per-site CpG methylation with a significant difference at CPG 1, 2, and 4 (p < 0.008). After propensity score matching, females maintained a significant survival benefit (18.7 vs. 10.0 months, p = 0.004) compared to males (13.0 vs. 13.6 months, p = 0.76), and the pattern of difference was significant (P for CpG-sex interaction = 0.03). Conclusions: In this study, females had higher mean and individual CpG site methylation and received a greater PFS and OS benefit by MGMT methylation that was not seen in males despite equal degrees of CpG methylation.

Low-grade papillary urothelial neoplasm: A case report study.

Urothelial carcinoma (UC) of the bladder is a prevalent malignant tumor among the elderly, whereas its incidence is scarce in the first 2 decades of life. The most commonly reported symptom in the literature is isolated hematuria, frequently overlooked during the initial medical assessment. In this study, we present the case of a 3-year-old male with hematuria, accompanied by other irritative symptoms such as flank pain, nausea, and vomiting. Ultrasonography revealed a bladder mass, which was later confirmed to be a noninvasive low-grade papillary urothelial carcinoma (NLPUC) through histopathological examination. This report discusses the clinical and pathological characteristics of the case and examines current literature on the topic.

Foreign bodies of body orifices: A pictorial review.

INTRODUCTION: Ingestion, inhalation, and insertion of foreign bodies (FB) are commonly encountered problems in the emergency departments (ED). Radiologists pay a key role in their diagnosis and management. Selecting an appropriate imaging modality is important depending on the route of entry and reported type of FB. Diagnosing FB is time sensitive and requires radiologists to be astute and familiar with varied imaging appearances of FB. In this article, we review imaging features of most common FB seen in clinical practice and their complications. TEACHING POINTS: SUMMARY: FB in body orifices are frequently seen in the ED. Imaging plays a pivotal role in the management in majority of the cases. In this article, we present several cases of commonly encountered FB.

Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study.

Background Pulmonary embolism (PE) commonly complicates SARS-CoV-2 infection, but incidence and mortality reported in single-center studies, along with risk factors, vary. Purpose To determine the incidence of PE in patients with COVID-19 and its associations with clinical and laboratory parameters. Materials and Methods In this HIPAA-compliant study, electronic medical records were searched retrospectively for demographic, clinical, and laboratory data and outcomes among patients with COVID-19 admitted at four hospitals from March through June 2020. PE found at CT pulmonary angiography and perfusion scintigraphy was correlated with clinical and laboratory parameters. The d-dimer level was used to predict PE, and the obtained threshold was externally validated among 85 hospitalized patients with COVID-19 at a fifth hospital. The association between right-sided heart strain and embolic burden was evaluated in patients with PE undergoing echocardiography. Results A total of 413 patients with COVID-19 (mean age, 60 years ± 16 [standard deviation]; age range, 20-98 years; 230 men) were evaluated. PE was diagnosed in 102 (25%; 95% CI: 21, 29) of 413 hospitalized patients with COVID-19 who underwent CT pulmonary angiography or perfusion scintigraphy. PE was observed in 21 (29%; 95% CI: 19, 41) of 73 patients in the intensive care unit (ICU) versus 81 (24%; 95% CI: 20, 29) of 340 patients who were not in the ICU (P = .37). PE was associated with male sex (odds ratio [OR], 1.74; 95% CI: 1.1, 2.8; P = .02); smoking (OR, 1.86; 95% CI: 1.0, 3.4; P = .04); and increased d-dimer (P < .001), lactate dehydrogenase (P < .001), ferritin (P = .001), and interleukin-6 (P = .02) levels. Mortality in hospitalized patients was similar between patients with PE and those without PE (14% [13 of 102]; 95% CI: 8, 22] vs 13% [40 of 311]; 95% CI: 9, 17; P = .98), suggesting that diagnosis and treatment of PE were not associated with excess mortality. The d-dimer levels greater than 1600 ng/mL [8.761 nmol/L] helped predict PE with 100% sensitivity and 62% specificity in an external validation cohort. Embolic burden was higher in patients with right-sided heart strain among the patients with PE undergoing echocardiography (P = .03). Conclusion Pulmonary embolism (PE) incidence was 25% in patients hospitalized with COVID-19 suspected of having PE. A d-dimer level greater than 1600 ng/mL [8.761 nmol/L] was sensitive for identification of patients who needed CT pulmonary angiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ketai in this issue.

Accuracy of Prostate Magnetic Resonance Imaging: Reader Experience Matters.

BACKGROUND: Prostate magnetic resonance imaging (MRI) is increasingly used in the detection, image-guided biopsy, and active surveillance of prostate cancer. The accuracy of prostate MRI may differ based on factors including imaging technique, patient population, and reader experience. OBJECTIVE: To determine whether the accuracy of prostate MRI varies with reader experience. DESIGN SETTING AND PARTICIPANTS: We rescored regions of interest from 194 consecutive patients who had undergone MRI/ultrasonography fusion biopsy. Original prostate MRI scans had been interpreted by one of 33 abdominal radiologists (AR group). More than 14 mo later, rescoring was performed by two blinded, prostate MRI radiologists (PR group). Likert scoring was used for both original MRI reports and rescoring. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of prostate MRI was defined for the AR and PR groups. A Likert score of 4-5 was considered test positive and clinically significant prostate carcinoma (csPCa; Gleason grade group [GGG] ≥2) was considered outcome positive. RESULTS AND LIMITATIONS: MRI-positive lesions (Likert 4-5) scored by the PR group resulted in csPCa more frequently than those scored by the AR group (64.9% vs 39.3%). MRI-negative lesions (Likert 2-3) were more likely to result in a clinically insignificant biopsy (benign pathology or GGG 1) when scored by the PR versus the AR group (91.8% vs 76.6%). Sensitivity and specificity of MRI to detect csPCa were higher for the PR group than for the AR group (sensitivity 85.9% vs 70.7%; specificity 77.3% vs 46.8%). Overall diagnostic accuracy was higher for the PR group than for the AR group (80.1% vs 54.6%). CONCLUSIONS: Sensitivity, specificity, PPV, and NPV of prostate MRI were higher for the PR group than for the AR group. PATIENT SUMMARY: We examined the accuracy of prostate magnetic resonance imaging (MRI) in two groups of radiologists. Experienced radiologists were more likely to detect clinically significant prostate cancer on MRI.

Sexually dimorphic radiogenomic models identify distinct imaging and biological pathways that are prognostic of overall survival in glioblastoma.

BACKGROUND: Recent epidemiological studies have suggested that sexual dimorphism influences treatment response and prognostic outcome in glioblastoma (GBM). To this end, we sought to (i) identify distinct sex-specific radiomic phenotypes-from tumor subcompartments (peritumoral edema, enhancing tumor, and necrotic core) using pretreatment MRI scans-that are prognostic of overall survival (OS) in GBMs, and (ii) investigate radiogenomic associations of the MRI-based phenotypes with corresponding transcriptomic data, to identify the signaling pathways that drive sex-specific tumor biology and treatment response in GBM. METHODS: In a retrospective setting, 313 GBM patients (male = 196, female = 117) were curated from multiple institutions for radiomic analysis, where 130 were used for training and independently validated on a cohort of 183 patients. For the radiogenomic analysis, 147 GBM patients (male = 94, female = 53) were used, with 125 patients in training and 22 cases for independent validation. RESULTS: Cox regression models of radiomic features from gadolinium T1-weighted MRI allowed for developing more precise prognostic models, when trained separately on male and female cohorts. Our radiogenomic analysis revealed higher expression of Laws energy features that capture spots and ripple-like patterns (representative of increased heterogeneity) from the enhancing tumor region, as well as aggressive biological processes of cell adhesion and angiogenesis to be more enriched in the "high-risk" group of poor OS in the male population. In contrast, higher expressions of Laws energy features (which detect levels and edges) from the necrotic core with significant involvement of immune related signaling pathways was observed in the "low-risk" group of the female population. CONCLUSIONS: Sexually dimorphic radiogenomic models could help risk-stratify GBM patients for personalized treatment decisions.

Intracystic Papillary Neoplasm of Gallbladder Mimicking Metastatic Malignancy on PET/CT.

ABSTRACT: Intracystic papillary neoplasm of the gallbladder is a rare preinvasive neoplastic lesion with similar characteristics as intraductal papillary mucinous neoplasm and other papillary neoplasms of pancreaticobiliary system. We report a case of 48-year-old woman with a history of recurrent right flank chondrosarcoma and gallbladder lesion on MRI and PET/CT interpreted as indeterminate for metastatic disease. Subsequent cholecystectomy showed intracystic papillary neoplasm. With gallbladder lesions being rare on PET/CT, this case illustrates the importance of considering both primary and secondary tumors in the differential diagnosis.

Radiogenomic-Based Survival Risk Stratification of Tumor Habitat on Gd-T1w MRI Is Associated with Biological Processes in Glioblastoma.

PURPOSE: To (i) create a survival risk score using radiomic features from the tumor habitat on routine MRI to predict progression-free survival (PFS) in glioblastoma and (ii) obtain a biological basis for these prognostic radiomic features, by studying their radiogenomic associations with molecular signaling pathways. EXPERIMENTAL DESIGN: Two hundred three patients with pretreatment Gd-T1w, T2w, T2w-FLAIR MRI were obtained from 3 cohorts: The Cancer Imaging Archive (TCIA; n = 130), Ivy GAP (n = 32), and Cleveland Clinic (n = 41). Gene-expression profiles of corresponding patients were obtained for TCIA cohort. For every study, following expert segmentation of tumor subcompartments (necrotic core, enhancing tumor, peritumoral edema), 936 3D radiomic features were extracted from each subcompartment across all MRI protocols. Using Cox regression model, radiomic risk score (RRS) was developed for every protocol to predict PFS on the training cohort (n = 130) and evaluated on the holdout cohort (n = 73). Further, Gene Ontology and single-sample gene set enrichment analysis were used to identify specific molecular signaling pathway networks associated with RRS features. RESULTS: Twenty-five radiomic features from the tumor habitat yielded the RRS. A combination of RRS with clinical (age and gender) and molecular features (MGMT and IDH status) resulted in a concordance index of 0.81 (P < 0.0001) on training and 0.84 (P = 0.03) on the test set. Radiogenomic analysis revealed associations of RRS features with signaling pathways for cell differentiation, cell adhesion, and angiogenesis, which contribute to chemoresistance in GBM. CONCLUSIONS: Our findings suggest that prognostic radiomic features from routine Gd-T1w MRI may also be significantly associated with key biological processes that affect response to chemotherapy in GBM.

Chylous ascites in cirrhosis from retroperitoneal lymphoma.

Chylous ascites occurs due to processes that elevate pressures within or obstruct the lymphatics in the retroperitoneum. In cirrhosis, spontaneous chylous ascites can occur but is uncommon. We describe a case of a 74-year-old man with cirrhosis from nonalcoholic steatohepatitis who presented with worsening abdominal distension and chylous ascites on paracentesis; an infiltrating retroperitoneal lymphoma was subsequently detected on computed tomography imaging.

Lynch Syndrome: Genomics Update and Imaging Review.

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.