ARAF protein kinase activates RAS by antagonizing its binding to RASGAP NF1.

RAF protein kinases are effectors of the GTP-bound form of small guanosine triphosphatase RAS and function by phosphorylating MEK. We showed here that the expression of ARAF activated RAS in a kinase-independent manner. Binding of ARAF to RAS displaced the GTPase-activating protein NF1 and antagonized NF1-mediated inhibition of RAS. This reduced ERK-dependent inhibition of RAS and increased RAS-GTP. By this mechanism, ARAF regulated the duration and consequences of RTK-induced RAS activation and supported the RAS output of RTK-dependent tumor cells. In human lung cancers with EGFR mutation, amplification of ARAF was associated with acquired resistance to EGFR inhibitors, which was overcome by combining EGFR inhibitors with an inhibitor of the protein tyrosine phosphatase SHP2 to enhance inhibition of nucleotide exchange and RAS activation.

First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial.

BACKGROUND: The addition of nivolumab to chemotherapy improves survival in patients with advanced oesophagogastric (oesophageal, gastric, or gastro-oesophageal junction) adenocarcinoma; however, outcomes remain poor. We assessed the safety and activity of regorafenib in combination with nivolumab and chemotherapy in the first-line treatment of advanced oesophagogastric adenocarcinoma. METHODS: This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with previously untreated, HER2-negative, metastatic oesophagogastric adenocarcinoma was done at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). Eligible patients had measurable disease or non-measurable disease that was evaluable (defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received FOLFOX chemotherapy (fluorouracil [400 mg/m2 bolus followed by 2400 mg/m2 over 48 h], leucovorin [400 mg/m2], and oxaliplatin [85 mg/m2]) and nivolumab (240 mg) intravenously on days 1 and 15, and oral regorafenib (80 mg) on days 1-21 of a 28-day cycle. Treatment was continued until disease progression (defined by RECIST version 1.1), unacceptable toxicity, or withdrawal of consent. The primary endpoint was 6-month progression-free survival in the per-protocol population (ie, all participants who received a dose of all study treatments). The regimen would be considered worthy of further investigation if at least 24 of 35 patients were progression free at 6 months. Safety was assessed in all participants who received at least one dose of any study treatment. This trial is registered with ClinicalTrials.gov, NCT04757363, and is now complete. FINDINGS: Between Feb 11, 2021, and May 4, 2022, 39 patients were enrolled, received at least one dose of study drug, and were included in safety analyses. 35 patients were evaluable for 6-month progression-free survival. Median age was 57 years (IQR 52-66), nine (26%) patients were women, 26 (74%) were men, 28 (80%) were White, and seven (20%) were Asian. At data cutoff (March 3, 2023), median follow-up was 18·1 months (IQR 12·7-20·4). The primary endpoint was reached, with 25 (71%; 95% CI 54-85) of 35 patients progression free at 6 months. Nine (26%) of 35 patients had disease progression and one (3%) patient died; the death was unrelated to treatment. The most common adverse event of any grade was fatigue (36 [92%] of 39). The most common grade 3 or 4 adverse events were decreased neutrophil count (18 [46%]), hypertension (six [15%]), dry skin, pruritus, or rash (five [13%]), and anaemia (four [10%]). Serious treatment-related adverse events occurred in ten (26%) patients, which were acute kidney injury (three [8%]), hepatotoxicity (two [5%]), sepsis (two [5%]), dry skin, pruritus, or rash (one [3%]), nausea (one [3%]), and gastric perforation (one [3%]). There were no treatment-related deaths. INTERPRETATION: Regorafenib can be safely combined with nivolumab and chemotherapy and showed promising activity in HER2-negative metastatic oesophagogastric cancer. A randomised, phase 3 clinical trial is planned. FUNDING: Bristol Myers Squibb, Bayer and National Institutes of Health/National Cancer Institute.

Extramural Venous Invasion and Tumor Deposit at Diffusion-weighted MRI in Patients after Neoadjuvant Treatment for Rectal Cancer.

Background Diffusion-weighted (DW) imaging is useful in detecting tumor in the primary tumor bed in locally advanced rectal cancer (LARC) after neoadjuvant therapy, but its value in detecting extramural venous invasion (EMVI) and tumor deposit is not well validated. Purpose To evaluate diagnostic accuracy and association with patient prognosis of viable EMVI and tumor deposit on DW images in patients with LARC after neoadjuvant therapy using whole-mount pathology specimens. Materials and Methods This retrospective study included patients who underwent neoadjuvant therapy and surgery from 2018 to 2021. Innovative five-point Likert scale was used by two radiologists to independently evaluate the likelihood of viable EMVI and tumor deposit on restaging DW MRI scans in four axial quadrants (12 to 3 o'clock, 3 to 6 o'clock, 6 to 9 o'clock, and 9 to 12 o'clock). Diagnostic accuracy was assessed at both the per-quadrant and per-patient level, with whole-mount pathology as the reference standard. Weighted κ values for interreader agreement and Cox regression models for disease-free survival and overall survival analyses were used. Results A total of 117 patients (mean age, 56 years ± 12 [SD]; 70 male, 47 female) were included. Pathologically proven viable EMVI and tumor deposit was detected in 29 of 117 patients (25%) and in 44 of 468 quadrants (9.4%). Per-quadrant analyses showed an area under the receiver operating characteristics curve of 0.75 (95% CI: 0.68, 0.83), with sensitivity and specificity of 55% and 96%, respectively. Good interreader agreement was observed between the radiologists (κ = 0.62). Per-patient analysis showed sensitivity and specificity of 62% and 93%, respectively. The presence of EMVI and tumor deposit on restaging DW MRI scans was associated with worse disease-free survival (hazard ratio [HR], 5.6; 95% CI: 2.4, 13.3) and overall survival (HR, 8.9; 95% CI: 1.6, 48.5). Conclusion DW imaging using the five-point Likert scale showed high specificity and moderate sensitivity in the detection of viable extramural venous invasion and tumor deposits in LARC after neoadjuvant therapy, and its presence on restaging DW MRI scans is associated with worse prognosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Méndez and Ayuso in this issue.

Rectal MRI Interpretation After Neoadjuvant Therapy.

In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Occurrence of peritoneal carcinomatosis in patients with rectal cancer undergoing staging pelvic MRI: clinical observations.

OBJECTIVES: Describe the cumulative incidence (CUIN) of peritoneal carcinomatosis (PC) and survival in patients presenting with advanced rectal cancer at staging pelvic MRI. METHODS: From 2013 to 2018, clinicopathologic records of patients with pretreatment rectal MRI clinical (c)T3c, cT3d, cT4a, and cT4b primary rectal adenocarcinoma were retrospectively reviewed by two radiologists. Standard MRI descriptors and pathologic stages were recorded. Recurrence-free (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Development of PC was explored using competing risk analysis. Differences in survival were compared using the log-rank test. Gray's test was used to test for differences in CUIN of PC. RESULTS: Three hundred forty-three patients (147 women; median age, 56 years) had MRI stages cT3cd, n = 170; cT4a, n = 40; and cT4b, n = 133. Median follow-up among survivors was 27 months (0.36-70 months). For M1 patients, OS differed only by cT stage (2-year OS: cT3 88.1%, cT4a 79.1%, cT4b 64.7%, p = 0.045). For M0 patients, OS and RFS differed only by pathological (p)T stage. We observed a statistically significant difference in the cumulative incidence of PC by cT stage (2-year CUIN: cT3 3.2%, cT4a 8.5%, cT4b 1.6%, p = 0.01), but not by pT stage. Seventy-nine patients (23%) presented with metastatic disease (M1), eight with PC (2.3%). Overall, eight patients presented with PC (cT4a: n = 4, other stages: n = 4) and 22 developed PC (cT4a: n = 5, other stages: n = 17). CONCLUSIONS: PC is uncommon in rectal cancer. MRI-based T stage exhibited an overall association with the cumulative incidence of PC, and descriptively, cT4a stage appears to have the highest CUIN. KEY POINTS: • In a retrospective study of 343 patients with rectal cancer undergoing baseline MRI and clinical follow-up, we found that peritoneal carcinomatosis was rare. • We observed a significant overall association between PC at presentation and cT stage that appeared to be driven by the higher proportion of cT4a patients presenting with PC. • Among patients that did not present with PC, we observed a significant overall association between time to PC and cT stage that may be driven by the higher cumulative incidence of PC in cT4a patients.

MRI radiomics features of mesorectal fat can predict response to neoadjuvant chemoradiation therapy and tumor recurrence in patients with locally advanced rectal cancer.

OBJECTIVE: To interrogate the mesorectal fat using MRI radiomics feature analysis in order to predict clinical outcomes in patients with locally advanced rectal cancer. METHODS: This retrospective study included patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal cancer from 2009 to 2015. Three radiologists independently segmented mesorectal fat on baseline T2-weighted axial MRI. Radiomics features were extracted from segmented volumes and calculated using CERR software, with adaptive synthetic sampling being employed to combat large class imbalances. Outcome variables included pathologic complete response (pCR), local recurrence, distant recurrence, clinical T-category (cT), post-treatment T category (ypT), and post-treatment N category (ypN). A maximum of eight most important features were selected for model development using support vector machines and fivefold cross-validation to predict each outcome parameter via elastic net regularization. Diagnostic metrics of the final models were calculated, including sensitivity, specificity, PPV, NPV, accuracy, and AUC. RESULTS: The study included 236 patients (54 ± 12 years, 135 men). The AUC, sensitivity, specificity, PPV, NPV, and accuracy for each clinical outcome were as follows: for pCR, 0.89, 78.0%, 85.1%, 52.5%, 94.9%, 83.9%; for local recurrence, 0.79, 68.3%, 80.7%, 46.7%, 91.2%, 78.3%; for distant recurrence, 0.87, 80.0%, 88.4%, 58.3%, 95.6%, 87.0%; for cT, 0.80, 85.8%, 56.5%, 89.1%, 49.1%, 80.1%; for ypN, 0.74, 65.0%, 80.1%, 52.7%, 87.0%, 76.3%; and for ypT, 0.86, 81.3%, 84.2%, 96.4%, 46.4%, 81.8%. CONCLUSION: Radiomics features of mesorectal fat can predict pathological complete response and local and distant recurrence, as well as post-treatment T and N categories. KEY POINTS: • Mesorectal fat contains important prognostic information in patients with locally advanced rectal cancer (LARC). • Radiomics features of mesorectal fat were significantly different between those who achieved complete vs incomplete pathologic response (accuracy 83.9%, 95% CI: 78.6-88.4%). • Radiomics features of mesorectal fat were significantly different between those who did vs did not develop local or distant recurrence (accuracy 78.3%, 95% CI: 72.0-83.7% and 87.0%, 95% CI: 81.6-91.2% respectively).

Rectal cancer with complete endoscopic response after neoadjuvant therapy: what is the meaning of a positive MRI?

OBJECTIVES: To determine the short-term outcomes of discordant tumor assessments between DWI-MRI and endoscopy in patients with treated rectal cancer when tumor-bed diffusion restriction is present ("+DWI"). METHODS: In this HIPPA-compliant, IRB-approved retrospective study, rectal MRI and endoscopic reports were reviewed for patients with locally advanced primary rectal adenocarcinoma (LARC) treated with chemoradiotherapy or total neoadjuvant therapy and imaged between January 2016 and December 2019. Eligible patients had a +DWI and endoscopy within 2 weeks of each other. True positive MRI were those with tumor on endoscopy and/or biopsy (TPa) or in whom endoscopy was negative for tumor, but subsequent 3-month follow-up endoscopy and DWI were both positive (TPb). The positive predictive value of DWI-MRI was calculated on a per-scan and per-patient basis. DWI-negative MRI exams were not explored in this study. RESULTS: In total, 397 patients with nonmetastatic primary LARC were analyzed. After exclusions, 90 patients had 98 follow-up rectal MRI studies with +DWI. Seventy-six patients underwent 80 MRI scans and had concordant findings at endoscopy (TPa). Seventeen patients underwent 18 MRI scans and had discordant findings at endoscopy (FP); among these, 4 scans in 4 patients were initially false positive (FP) but follow-up MRI remained +DWI and the endoscopy turned concordantly positive (TPb). PPV was 0.86 per scan and per patient. In 4/18 (22%) scans and 4/17 (24%) patients with discordances, MRI detected tumor regrowth before endoscopy. CONCLUSIONS: Although most +DWI exams discordant with endoscopy are false positive, 22% will reveal that DWI-MRI detects tumor recurrence before endoscopy. KEY POINTS: • Most often, in post-treatment assessment for rectal cancer when DWI-MRI shows restriction in the tumor bed and endoscopy shows no tumor, +DWI MRI will be proven false positive. • Conversely, our study demonstrated that, allowing for sequential follow-up at a 3-month maximum interval, DWI-MRI may detect tumor presence in the treated tumor bed before endoscopy in 22% of discordant findings between DWI-MRI and endoscopy. • Our results showed that a majority of DWI-MRI-positive scans in treated rectal cancer concur with the presence of tumor on endoscopy performed within 2 weeks.

Abdominal imaging findings on computed tomography in patients acutely infected with SARS-CoV-2: what are the findings?

OBJECTIVES: To investigate what findings are new on contrast-enhanced abdominopelvic CT in patients infected with SARS-CoV-2. METHODS: Contrast-enhanced CT of the abdomen and pelvis of patients with COVID-19 at a tertiary oncologic center acquired over a 2-month period were reviewed independently by two readers and scored for new imaging abnormalities compared with a prior scan. CT scans were included if the study was performed between - 3 and 45 days from the time of COVID-19 diagnosis. Clinical information was gathered from the medical records. RESULTS: A total of 63 patients (34 male, 29 female; mean age 60.6 years, range 24.4-85.0 years) were included in this retrospective cross-sectional study. Aside from new ground glass opacities seen at the lung bases (29/63, 46.0%), the most common findings were new thickening of the stomach, small bowel or colon or fluid-filled colon (14/63, 22.2%), new small volume ascites (7/63, 14.3%), gallbladder distention in those without prior cholecystectomy (3/43, 7.0%), and single cases each of acute pancreatitis (1/63, 1.6%) as well as new portal vein thrombosis (1/63, 1.6%). CONCLUSION: Aside from lung base ground glass opacities, the most common new imaging abnormality on abdominopelvic CT in patients with COVID-19 finding in our cohort was abnormalities of the gastrointestinal tract, followed by small volume ascites, gallbladder distention, and isolated cases of pancreatitis and portal vein thrombosis. These findings overlap with those previously reported that did not have a prior scan for comparison, and provide supportive evidence that some of these findings may be related to SARS-CoV-2 infection.

Role of Imaging in Esophageal Cancer Management in 2020: Update for Radiologists.

OBJECTIVE. The purpose of this article is to discuss the role of imaging in the management of esophageal cancer. CONCLUSION. A multimodality-based approach to imaging is essential in clinical practice to achieve the best possible outcome for patients with esophageal cancer. Radiologists must be aware of the strengths and limitations of different imaging modalities in various clinical settings. The role of a radiologist is to combine information from anatomic and functional imaging, assess metastatic disease and changes in the primary tumor during treatment, and identify anatomic complications after treatment.

Comparison of International Ovarian Tumor Analysis Simple Rules to Society of Radiologists in Ultrasound Guidelines for Detection of Malignancy in Adnexal Cysts.

OBJECTIVE. The purpose of this study was to evaluate the International Ovarian Tumor Analysis (IOTA) simple rules and the Society of Radiologists in Ultrasound (SRU) guidelines for detecting ovarian malignancy in a general population of women presenting to radiology departments with adnexal cystic lesions. MATERIALS AND METHODS. A retrospective multicenter study of ultrasound-detected adnexal cystic lesions with appropriate follow-up was conducted. Lesions were classified into benign, indeterminate, or malignant categories according to criteria based on the IOTA simple rules and the SRU guidelines. The prevalence of nonneoplastic cysts, neoplasms, and malignant tumors was calculated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated, and ROC analysis for the diagnosis of malignancy was performed. RESULTS. A total of 697 women with 764 cystic lesions were included; 85.2% (651/764) of the lesions were nonneoplastic, 12.2% (93/764) were benign neoplasms, and 2.6% (20/764) were malignant neoplasms. Nearly all malignancies were classified into indeterminate and malignant categories. The prevalence of malignancy in the indeterminate category was 4.8% (7/145) (SRU) to 10.7% (7/65) (IOTA) and in the malignant category was 18.1% (13/72) (SRU) to 34.3% (12/35) (IOTA). Only one malignancy was misclassified as benign by the IOTA simple rules. The sensitivity of the IOTA simple rules for malignancy was 90.0%; specificity, 96.5%; PPV, 29.0%; NPV, 99.8%; and accuracy, 96.4%. The corresponding values for the SRU guidelines were 100%, 89.6%, 14.9%, 100%, and 89.8%. In ROC analysis, the IOTA simple rules were slightly more accurate than the SRU guidelines (AUC, 0.9805 versus 0.9713; p = 0.0003). CONCLUSION. Both imaging characterization methods were sensitive for identifying ovarian malignancies, but the PPV was low among women presenting to radiology departments, and the indeterminate classification harbored one-third of the total malignancies. Exploration of varied clinical settings and inclusion of secondary tests may help to refine these systems.

The relationship between adrenal incidentalomas and mortality risk.

OBJECTIVE: To determine all-cause mortality risk in patients with and without adrenal incidentaloma. METHODS: Retrospective cohort study of patients with CT abdomen performed within 24 h of emergency room presentation at an academic medical center from January 1, 2005, to December 31, 2009, without history of adrenal disease, adrenal lab testing, or cancer. Incidentaloma cohort identified by database query of imaging reports followed by manual review and matched to no-nodule controls at 3:1 on age ± 1 year and exam date ± 3 months. Mortality ascertained by in-hospital deaths and National Death Index query. Survival analysis performed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Among 42,575 adults with abdominal CT exams, 969 adrenal incidentaloma patients and 2907 no-nodule controls were identified. All 3876 individuals entered survival analysis with 31,182 person-years at risk (median follow-up 8.9 years [IQR, 6.9-10.7]). All-cause mortality was significantly higher among those with adrenal incidentalomas (353/969, 36.4%) compared with those without (919/2907, 31.6%; mortality difference 7.6 per 1000 person-years; multivariable-adjusted hazard ratio [aHR] 1.14; 95% CI, 1.003-1.29). Exploratory analyses, limited by missing covariates, found that adrenal incidentalomas were associated with significantly increased incidence of malignancy (aHR 1.61; 95% CI, 1.22-2.12), diabetes (aHR 1.43; 95% CI, 1.18-1.71), heart failure (aHR 1.32; 95% CI, 1.07-1.63), peripheral vascular disease (aHR 1.28; 95% CI, 1.95-1.56), renal disease (aHR 1.21; 95% CI, 1.01-1.44), and chronic pulmonary disease (aHR 1.22; 95% CI, 1.01-1.46) compared with controls. CONCLUSIONS: Adrenal incidentalomas are associated with increased mortality and may represent a clinically valuable biomarker. KEY POINTS: • Adrenal incidentalomas are associated with increased mortality. • Adrenal incidentaloma size is not predictive of mortality. • On exploratory analyses, adrenal incidentalomas are associated with chronic illnesses.

MRI of Tumors and Tumor Mimics in the Female Pelvis: Anatomic Pelvic Space-based Approach.

Pelvic masses can present a diagnostic challenge owing to the difficulty in assessing their origin and the overlap in imaging features. The majority of pelvic tumors arise from gastrointestinal or genitourinary organs, with less common sites of origin including the connective tissues, nerves, and lymphovascular structures. Lesion evaluation usually starts with clinical assessment followed by imaging, or the lesion may be an incidental finding at imaging performed for other clinical indications. Since accurate diagnosis is essential for optimal management, imaging is useful for suggesting the correct diagnosis or narrowing the differential possibilities and distinguishing tumors from their mimics. Some masses may require histologic confirmation of the diagnosis with biopsy and/or up-front surgical resection. In this case, imaging is essential for presurgical planning to assess mass size and location, evaluate the relationship to adjacent pelvic structures, and narrow differential possibilities. Pelvic US is often the first imaging modality performed in women with pelvic symptoms. While US is often useful to detect a pelvic mass, it has significant limitations in assessing masses located deep in the pelvis or near gas-filled organs. CT also has limited value in the pelvis owing to its inferior soft-tissue contrast. MRI is frequently the optimal imaging modality, as it offers both multiplanar capability and excellent soft-tissue contrast. This article highlights the normal anatomy of the pelvic spaces in the female pelvis and focuses on MRI features of common tumors and tumor mimics that arise in these spaces. It provides an interpretative algorithm for approaching an unknown pelvic lesion at MRI. It also discusses surgical management, emphasizing the value of MRI as a road map to surgery and highlighting anatomic locations where surgical resection may present a challenge. ©RSNA, 2019.

Indeterminate Adnexal Cysts at US: Prevalence and Characteristics of Ovarian Cancer.

Purpose To assess the prevalence of indeterminate adnexal cysts in women presenting to academic medical centers for pelvic ultrasonography (US), determine the incidence of malignancy, and identify cyst and patient characteristics that are predictive of malignancy. Materials and Methods A multicenter study of US-detected adnexal cysts with appropriate follow-up (surgical pathologic examination, imaging and/or clinical examination) was conducted from January 2008 to June 2012. Indeterminate cysts were classified as category 1 (typical benign appearing cysts >5 cm) or category 2 (cysts with avascular solid components) on the basis of a combination of definitions in the existing literature. The incidence of neoplasms and malignant tumors was calculated. Patient and cyst characteristics associated with neoplasm and malignant tumors were evaluated with the χ2 test or Fisher exact test for categorical variables and the t test for continuous variables. A backward stepwise logistic regression model was performed for two outcomes: (a) the presence of any neoplasm (benign or malignant) and (b) the presence of a malignant tumor. Results There were 1637 women with an adnexal cyst at US; 391 (mean age = 41.8 years ± 13.5.1; range = 17-91 years) had an indeterminate adnexal cyst at US. The prevalence of indeterminate adnexal cysts was 23.9% (391 of 1637; 95% confidence interval [CI]: 0.22, 0.26). Three hundred three indeterminate cysts in 280 women (mean age = 42.9 years ± 14.1; range = 17-88 years) had adequate follow-up. The incidence of ovarian neoplasms (benign and malignant) was 24.8% (75 of 303 cysts; 95% CI: 0.20, 0.30), and the incidence of malignant tumors was 3.6% (11 of 303 cysts; 95% CI: 0.02, 0.06). The proportion of ovarian neoplasms differed between category 1 and category 2 cysts (17.5% [25 of 143 cysts; 95% CI: 0.12, 0.25] vs 31.3% [50 of 160 cysts; 95% CI: 0.24, 0.39], respectively; P = .001). The proportion of malignant tumors differed between categories 1 and 2 cysts (0% [0 of 143 cysts] vs 6.9% [11 of 160 cysts; 95% CI: 0.03, 0.12]; P < .001). The presence of an avascular nodular component was a significant predictor of malignancy at stepwise logistic regression analysis (odds ratio = 2.83; P ≤ .0001; 95% CI: 1.69, 4.70). Conclusion The presence of an avascular nodular component was the most significant predictor of the presence of malignancy in indeterminate adnexal cysts. The risk of malignancy is higher with category 2 cysts than with category 1 cysts. © RSNA, 2018.

Practical guide to dynamic pelvic floor MRI.

Pelvic floor dysfunction encompasses a spectrum of functional disorders that result from impairment of the ligaments, fasciae, and muscles supporting the pelvic organs. It is a prevalent disorder that carries a lifetime risk over 10% for undergoing a surgical repair. Pelvic floor weakness presents as a wide range of symptoms, including pain, pelvic pressure or bulging, urinary and fecal incontinence, constipation, and sexual dysfunction. A correct diagnosis by clinical examination alone can be challenging, particularly in cases involving multiple compartments. Magnetic resonance imaging (MRI) allows noninvasive, radiation-free, high soft-tissue resolution evaluation of all three pelvic compartments, and has proved a reliable technique for accurate diagnosis of pelvic floor dysfunction. MR defecography with steady-state sequences allows detailed anatomic and functional evaluation of the pelvic floor. This article provides an overview of normal anatomy and function of the pelvic floor and discusses a practical approach to the evaluation of imaging findings of pelvic floor relaxation, pelvic organ prolapse, fecal incontinence, and obstructed defecation. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1155-1170.

Liver Imaging Reporting and Data System: Discordance Between Computed Tomography and Gadoxetate-Enhanced Magnetic Resonance Imaging for Detection of Hepatocellular Carcinoma Major Features.

PURPOSE: The goal of this study was to compare agreement between computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of the major Liver Imaging Reporting and Data System (LI-RADS) features used in assessment of hepatocellular carcinoma: arterial phase hyperenhancement (APHE), portal venous phase washout (WO), capsule appearance (capsule), and largest diameter (diameter). METHODS: Patients with liver protocol CT and gadoxetate-enhanced MRI within 1 month of each other and at least 1 discrete untreated liver lesion were included. Two readers independently reviewed hepatic arterial phase and portal venous phase of each lesion on both CT and MRI, presented at random. The APHE, WO, capsule, and diameter were assessed for each lesion on CT and MRI. The LI-RADS category was assigned based on the recorded major features. Interobserver agreements between the readers for both imaging modalities and for each of the major features were assessed using κ statistics. Agreement between CT and MRI for each reader and for each feature was assessed using κ statistics. Agreement was interpreted based on κ as follows: 0.20 or less, slight agreement; 0.21 to 0.40, fair agreement; 0.41 to 0.60, moderate agreement; 0.61 to 0.80, substantial agreement; and 0.81 to 1.00, almost perfect agreement. Intraclass correlation coefficient was used to assess concordance of diameter measurements. RESULTS: There were 42 patients (mean age, 62.2 ± 7.0 years; 33 men [78.6%]) with 50 lesions. On CT, the interobserver agreement between the readers was almost perfect for APHE (κ = 0.85), WO (κ = 0.83), and capsule (κ = 0.86). On MRI, the interobserver agreement between the readers was almost perfect for APHE (κ = 0.86) and WO (κ = 0.83) and moderate for capsule (κ = 0.59). Intraclass correlation coefficient for diameter measurement was 0.99 for CT and 0.98 for MRI. For reader 1, the agreement between CT and MRI was fair for APHE (κ = 0.39) and capsule (κ = 0.26) and moderate for WO (κ = 0.49). For reader 2, the agreement between CT and MRI was moderate for APHE (κ = 0.43) and capsule (κ = 0.43) and fair (κ = 0.38) for WO. Agreement between readers for final LI-RADS category was substantial for CT (κ = 0.79) and moderate for MRI (κ = 0.60). Agreement for final LI-RADS categories between MRI and CT was fair for both reader 1 (κ = 0.33) and reader 2 (κ = 0.39). CONCLUSIONS: Interobserver agreement for the major LI-RADS features varies from moderate to almost perfect, for both CT and MRI. However, the agreement between CT and MRI for each of the major LI-RADS features is poor, ranging from fair to moderate. This poor agreement contributes to substantial differences between final LI-RADS category assigned on CT versus MRI.

Diagnosis of acute cholecystitis: why do patients get multiple studies?

The aim of this study is to establish factors affecting total number of imaging studies performed for acute cholecystitis (AC) prior to surgery. The study included subjects with cholecystectomy and pathologic diagnosis of AC 1/1/05-1/1/14 and imaging studies (computed tomography (CT), ultrasound (US), and/or cholescintigraphy) within 7 days of surgery. The subjects were separated into groups based on modality of the first study. For each subject, report of the first study was reviewed for report's confidence in diagnosis of AC (scored 1-5 on Likert scale: 5 = definitely AC, 1 = definitely no AC), recommendation of additional study, clinical history concerning for AC (history of right upper quadrant pain, cholelithiasis, and/or "rule out AC"). There were 219, 339, and 38 subjects in CT, US, and cholescintigraphy groups, respectively, with mean confidence scores of 3.7 (± 1.2), 3.7 (± 1.1), and 4.7 (± 0.9), respectively (p < 0.001). Prior to surgery, only one study was performed in 21.9 % (48/219) of CT group, 70.2 % (238/339) of US group, and 71.1 % (27/38) of cholescintigraphy group (p < 0.0001). Compared to the US group, the odds of undergoing additional study were 11.8 times higher (p < 0.001) in CT group and 1.7 times higher (p = 0.229) in cholescintigraphy group, adjusting for age, sex, time interval between first study and the surgery, confidence score, recommendation of follow-up study, and clinical history concerning for AC. Patients with AC and CT as the first study are more likely to undergo additional imaging studies prior to surgery as compared to US or cholescintigraphy.

The iodide-transport-defect-causing mutation R124H: a δ-amino group at position 124 is critical for maturation and trafficking of the Na+/I- symporter.

Na(+)/I(-) symporter (NIS)-mediated active accumulation of I(-) in thyrocytes is a key step in the biosynthesis of the iodine-containing thyroid hormones T3 and T4. Several NIS mutants have been identified as a cause of congenital I(-) transport defect (ITD), and their investigation has yielded valuable mechanistic information on NIS. Here we report novel findings derived from the thorough characterization of the ITD-causing mutation R124H, located in the second intracellular loop (IL-2). R124H NIS is incompletely glycosylated and colocalizes with endoplasmic reticulum (ER)-resident protein markers. As a result, R124H NIS is not targeted to the plasma membrane and therefore does not mediate any I(-) transport in transfected COS-7 cells. Strikingly, however, the mutant is intrinsically active, as revealed by its ability to mediate I(-) transport in membrane vesicles. Of all the amino acid substitutions we carried out at position 124 (K, D, E, A, W, N and Q), only Gln restored targeting of NIS to the plasma membrane and NIS activity, suggesting a key structural role for the δ-amino group of R124 in the transporter's maturation and cell surface targeting. Using our NIS homology model based on the structure of the Vibrio parahaemolyticus Na(+)/galactose symporter, we propose an interaction between the δ-amino group of either R or Q124 and the thiol group of C440, located in IL-6. We conclude that the interaction between IL-2 and IL-6 is critical for the local folding required for NIS maturation and plasma membrane trafficking.

Advances in the Imaging of Esophageal and Gastroesophageal Junction Malignancies.

Accurate imaging is key for the diagnosis and treatment of esophageal and gastroesophageal junction cancers . Current imaging modalities, such as computed tomography (CT) and 18F-FDG (2-deoxy-2-[18F]fluoro-D-glucose) positron emission tomography (PET)/CT, have limitations in accurately staging these cancers. MRI shows promise for T staging and residual disease assessment. Novel PET tracers, like FAPI, FLT, and hypoxia markers, offer potential improvements in diagnostic accuracy. 18F-FDG PET/MRI combines metabolic and anatomic information, enhancing disease evaluation. Radiomics and artificial intelligence hold promise for early detection, treatment planning, and response assessment. Theranostic nanoparticles and personalized medicine approaches offer new avenues for cancer therapy.

Watch & wait - Post neoadjuvant imaging for rectal cancer.

Rectal cancer management has evolved over the past decade with the emergence of total neoadjuvant therapy (TNT). For select patients who achieve a clinical complete response following TNT, organ preservation by means of the watch-and-wait (WW) strategy is an increasingly adopted alternative that preserves rectal function and quality of life without compromising oncologic outcomes. Recently, published 5-year results from the OPRA trial demonstrated that organ preservation can be achieved in approximately half of patients managed with the WW strategy, with most local regrowth events occurring within two years. Considering the potential for local regrowth, the implementation of the WW strategy mandates rigorous clinical and radiographic surveillance. Magnetic resonance imaging (MRI) serves as the conventional imaging modality for local staging and surveillance of rectal cancer given its excellent soft-tissue resolution. This review will discuss the current evidence for the WW strategy and the role of restaging rectal MRI in determining patient eligibility for this strategy. Restaging rectal MRI acquisition parameters and treatment response assessment, including important factors to assess, pitfalls, and classification systems, will be discussed in the context of the WW strategy.