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Please see the Editorial Comment by Candice Bolan discussing this article. The treatment of rectal cancer centers around the distinct but related goals of management of distant metastases and manag...

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., Take Home Message The utility of prostate magnetic resonance imaging to accurately detect clinically significant prostate cancer depends on the radiologist’s experience. Both histopathological feedback and volume of interpretations are likely important for the development of expertise.

Both transperineal and transrectal ultrasound (TRUS)-guided systematic biopsy are accepted methods to diagnose prostate cancer (PCa). However, systematic sampling misses up to 47% of tumors 0.5 mL or larger and under-represents the tumor grade in 38% of cases [1,2]. These shortcomings result in underestimated risk and repeat prostate biopsies.

To identify the optimum response criteria for first-line targeted pazopanib therapy in patients with mRCC using solid tumor response criteria and clinical risk factors. Pre- and post-treatment CTs of patients (n = 43) with mRCC treated with first-line pazopanib therapy were analyzed retrospectively. Treatment response was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Choi, modified Choi (mChoi), revised Choi (rChoi), MASS (Morphology, Attenuation, Size, and Structure), 10% threshold criteria, and subjective assessment. Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium clinical risk factors were also used to define response groups. Response evaluations were correlated with overall survival (OS) and progression-free survival (PFS) using log-rank test. Patients with partial response (PR) by mChoi and rChoi had longer OS than those with stable disease (SD) (P

The treatment of rectal cancer centers around the distinct but related goals of management of distant metastases and management of local disease. Optimal local management requires attention to the primary tumor and its anatomic relationship to surrounding pelvic structures, with the goal of minimizing local recurrence (LR). High-resolution MRI is ideally suited for this purpose; application of MRI-based criteria in conjunction with optimized surgical and pathologic techniques has successfully reduced LR rates. This success has led to a shift away from using the TNM-based National Comprehensive Cancer Network (NCCN) guidelines as the sole determinant of whether a patient receives neoadjuvant chemoradiation. The new model uses a hybrid approach for assigning risk categories that combines elements of the TNM staging system with MRI-based anatomic features. These risk categories incorporate tumor proximity to the circumferential resection margin, T category, distance to the anal verge, and presence of extramural venous invasion to classify rectal tumors as low, intermediate, or high risk. This approach has been validated by accumulated data from numerous multiinstitutional studies. This article illustrates key anatomic concepts, depicts common interpretive errors and pitfalls, and discusses ongoing limitations; these insights should guide radiologists in optimal rectal MRI interpretation.

Tuberous sclerosis complex is a multiorgan syndrome manifesting with several benign and malignant tumors. Complications arising from renal abnormalities are a leading cause of death in patients with tuberous sclerosis complex. Renal cell carcinoma is relatively uncommon, occurring in 2%-4% of patients with tuberous sclerosis complex syndrome, but nonetheless can significantly contribute to morbidity and mortality. Extrarenal manifestations of tuberous sclerosis complex, including within the chest, abdomen and central nervous system, aid in diagnosis. Pathogenesis and management are also discussed, including the importance of the types of renal masses found in these patients.

ObjectiveTo compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages.MethodsVUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling.ResultsQuantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney.ConclusionsSignificant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging.

After resection of colorectal liver metastases (CLM), up to 40% of patients will develop intrahepatic recurrence. This study aims to identify patterns of intrahepatic recurrence and their impact on survival after preoperative chemotherapy and CLM resection. A retrospective review was performed of patients developing intrahepatic recurrence after CLM resection following preoperative chemotherapy. Prechemotherapy, preoperative, and postoperative computed tomography scans were reviewed. Recurrences were classified as in situ, de novo, or both in situ and de novo. Median follow-up was 42 months (range 2–144 months). Among 223 patients meeting study criteria, intrahepatic recurrence was identified a median of 9 months after hepatectomy. Isolated de novo or in situ recurrence developed in 105 (47%) and 86 (39%) patients, respectively. Thirty-two patients (14%) developed both in situ and de novo recurrence, which was associated with significantly lower median overall survival of 33 months compared with 49 and 45 months with isolated in situ or de novo recurrence, respectively (p = 0.048). Among 118 patients (53%) who developed in situ recurrence as a component of disease relapse, recurrences resulted from disappearing or missed liver metastases in 47 patients (40%). An intrahepatic recurrence pattern of both in situ and de novo metastases after CLM resection following preoperative chemotherapy predicts significantly worse overall survival compared with isolated in situ or de novo recurrence.

Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis.We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients' outcomes.Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016).Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.

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.

The purpose of this study is to compare the prognostic value of various solid tumor response criteria as well as the additive value of clinical risk factors in patients with advanced renal cell carcinoma (RCC).Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months after treatment) were reviewed for 57 patients with metastatic RCC treated with pazopanib in the salvage setting. Tumor response on the posttherapy scan was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi, modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and 10% threshold criteria. In addition, combined Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors plus imaging criteria were used to define response groups. Response evaluations using these criteria were correlated with overall survival (OS) and progression-free survival (PFS), with use of the log-rank test.Patients classified as having progressive disease (PD) on the basis of RECIST, mChoi, and MASS criteria had a significantly worse OS than patients with stable disease (SD) and partial response (PR). With the addition of MSKCC risk factors, all groups with PD defined by combined criteria had significantly worse OS. For 37 patients with no or one MSKCC risk factor, response groups defined by Choi, mChoi, MASS, and 10% threshold criteria did not differ in PFS or OS. However, among 20 patients with two to three MSKCC risk factors, those classified as having PR had longer PFS than did those with SD and had longer OS than did those with PD.For patients with advanced RCC for which prior therapies have failed, the prognostic value of various imaging-based tumor response criteria differs on the basis of the MSKCC clinical risk status.

Purpose To compare the effectiveness of metastatic tumor response evaluation with computed tomography using computer-assisted versus manual methods. Materials and Methods In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study, 11 readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria by using paired baseline and initial post-therapy computed tomography studies from 20 randomly selected patients with metastatic renal cell carcinoma who were treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard of care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data and image archiving. A crossover design, patient randomization, and 2-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. Results The standard-of-care method, on average, was associated with one or more errors in 30.5% (6.1 of 20) of patients, whereas CARE had a 0.0% (0.0 of 20) error rate ( P < .001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range, 1 to 3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 minutes v 13.1 minutes; P < .001). Conclusion CARE reduced errors and time of evaluation, which indicated better overall effectiveness than manual tumor response evaluation methods that are the current standard of care.

BACKGROUND Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit. METHODS Hybrid capture–based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients. Clinical variables, detected mutations, and administered therapies were correlated with overall survival (OS) in a Cox regression model. RESULTS The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA. Fibroblast growth factor receptor (FGFR; 11%) and IDH mutations (20%) were mostly limited to IHCCA but appeared to be mutually exclusive. In the IHCCA group, TP53 and KRAS mutations were associated significantly with poor OS, whereas FGFR2 mutations were associated with improved OS (P = .001), a younger age at onset, and female sex. IDH1/2 mutations were not prognostic. In a multivariate model, the effects of TP53 and FGFR GAs remained significant (P

OBJECTIVE. The purpose of this article is to discuss the histopathologic features, genetics, clinical presentation, and imaging of hereditary renal cancer syndromes. CONCLUSION. Hereditary renal cell carcinoma syndromes can be diagnosed with a pattern-based approach focused on the predominant histologic renal cell carcinoma subtype and associated renal and extrarenal features of each syndrome.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant inherited syndrome involving multiple organs. In young patients, renal neoplasms that are multiple, bilateral, or both, such as oncocytomas, chromophobe renal cell carcinoma (RCC), hybrid chromophobe RCC-oncocytomas, clear cell RCC, and papillary RCC, can suggest BHD syndrome. Extrarenal findings, including dermal lesions, pulmonary cysts, and spontaneous pneumothoraces, also aid in diagnosis.Radiologists may be one of the first medical specialists to suggest the diagnosis of BHD syndrome. Knowledge of pathogenesis and management, including the importance of the types of renal neoplasms in a given patient, is needed to properly recognize this rare condition.

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.

Renal cell carcinoma is the most common malignant renal tumor in the adults. Significant advances have been made in the management of localized and advanced renal cell carcinoma. Surgery is the standard of care and accurate pre-operative staging based on imaging is critical in guiding appropriate patient management. Besides staging, imaging plays a key role in the post-operative surveillance and evaluation of response to systemic therapies. Both CT and MR are useful in the staging and follow up of renal cell carcinoma, but CT is more commonly used due to its lower costs and wider availability. In this article, we discuss and illustrate the role of multi-detector CT in pre-operative staging, post-operative surveillance, and evaluation of response to systemic therapy in renal cell carcinoma.

BACKGROUND Preclinical and clinical studies suggest mTOR (mammalian target of rapamycin) inhibitors may have metabolic and antiangiogenic effects, and synergize with epidermal growth factor pathway inhibitors. Therefore, a phase 1/pharmacodynamic trial of everolimus with cetuximab was performed. METHODS A total of 29 patients were randomized to a run-in of oral everolimus (30, 50, or 70 mg) or cetuximab (400 mg/m2 loading, 250 mg/m2 maintenance) weekly, followed by the combination in this dose-escalation study. Primary endpoints were phase 2 dose and toxicity characterization. [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed as a pharmacodynamic marker of mTOR inhibition, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed as an indicator of tumor perfusion changes, at 3 time points. RESULTS Everolimus and cetuximab were tolerable at full doses, with an expected toxicity profile. Dose-limiting toxicities in the everolimus 70 mg group included grade 3 skin toxicity in 2 patients, and mucositis in 1 patient. Of 16 patients evaluable for response, 5 had stable disease lasting 4 to 19 months. Mean change in maximum standardized uptake value (SUVmax) for those treated initially with everolimus was −24% (2% to −54%), and with cetuximab was −5% (−23 to 36%). The Ktrans measured by DCE-MRI did not decrease, regardless of run-in drug. CONCLUSIONS Everolimus and cetuximab can be safely administered at standard doses, and are associated with prolonged disease control. The recommended phase 2 dose of oral weekly everolimus is 70 mg in combination with standard cetuximab. Imaging studies reveal that metabolic inhibition by everolimus alone and in combination with cetuximab predominates over changes in tumor perfusion in this patient population. Cancer 2014;120:77–85. © 2013 American Cancer Society.

The purpose of this study was to examine early MRI changes in renal cell carcinoma (RCC) treated with the antiangiogenic agent sorafenib and to identify MRI biomarkers of RCC response to sorafenib.Sixteen patients with RCC were evaluated by MRI before and 3-12 weeks after commencing treatment with sorafenib. Two experienced MR radiologists, blinded to treatment status, independently graded tumor appearance on T1-weighted, T2-weighted, and gadolinium-enhanced images. The proportional odds mixed model was used to compare qualitative appearance of tumors before and after therapy. Time-to-progression was correlated with Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and MR-modified Choi criteria, incorporating changes in both tumor enhancement and size.After sorafenib therapy, there was a significant increase in T1 signal intensity of tumors (p0.0001) and a significant decrease in degree of tumor enhancement (p0.0001). The sum of unidimensional tumor diameters decreased significantly after therapy (p = 0.005). However, the average decrease in size at early follow-up was 13%, and all patients except one had stable disease by RECIST 1.0. Early responders defined by MR-modified Choi criteria had increased time-to-progression compared with nonresponders, whereas early RECIST evaluation did not predict clinical outcome.Decreased enhancement and T1 shortening of tumors on MRI may be useful biomarkers of RCC response to angiogenesis inhibitors. Response criteria combining early changes in size and enhancement lead to better correlation with clinical outcome compared with size decrease alone.

The portal pedicles are wrapped in connective tissue known as the Walaeus sheath, which abut Laennec's capsule covering the liver parenchyma. Precise knowledge of this anatomic relationship allows for dissection of this interspace and early control of the segmental portal pedicle (Glissonean pedicle transection method [GPTM], Takasaki approach).The patient was a 60-year-old healthy woman with invasive lobular breast cancer, grade 2, which was estrogen receptor-positive (ER +), progesterone receptor-positive (PR +), human epidermal growth factor-negative (HER2-), Ki-67 80%, and cT2N0M1. A synchronous solitary liver metastasis between segments 6 and 7 was diagnosed. After treatment with letrozole and palbociclib for 1 year had achieved stable disease, the patient was considered for liver metastasectomy.Laparoscopic application of GPTM facilitates anatomically precise liver resection through early pedicle control. Negative counterstaining using ICG under near-infrared vision leads to visual enhancement of the anatomically precise borders. They typically do not follow straight lines and are therefore difficult to dissect precisely. Counterstaining with ICG shows patient-specific anatomic variations that would be a challenge to determine, especially laparoscopically.

While the oncologic safety of minimally invasive hepatectomy for colorectal liver metastases (CLM) has been demonstrated, lesions in the postero-superior segments may be challenging.1 – 3 For these lesions, a transthoracic approach may be particularly helpful, especially in patients with a hostile/reoperative abdomen or morbid obesity.4 , 5 A 43-year-old man with a body mass index of 36.0 who had undergone rectosigmoid resection for primary cancer 5 years ago recurred with a solitary liver metastasis in SVIII. He had previously undergone the following resections for metachronous CLM: (i) partial resections of SV/VIII and SII/III; (ii) ablation for SVII; and (iii) left hepatectomy, common bile duct resection, and choledochojejunostomy. Following four cycles of FOLFIRI/panitumumab with good response, the patient was considered for his fourth abdominal cancer intervention via a thoracoscopic approach. In a modified French position with left-lung ventilation, access to the right thoracic cavity was gained. Following thoracic adhesiolysis, transdiaphragmatic intraoperative ultrasonography (IOUS) was performed. To ensure optimal margins, IOUS-guided transthoracic hepatic resection with partial resection of the diaphragm was conducted. The diaphragm was reconstructed and a chest tube placed. Operative time was 247 min, with an estimated blood loss of 100 mL. Postoperative recovery was uneventful; pathology demonstrated no viable tumor, with the closest margin 5 mm from the necrotic area. Transthoracic hepatic resection of SVIII can optimize the port–target axis while minimizing morbidity. A systematic approach that includes precise port positioning, non-traumatic intrathoracic adhesiolysis, and meticulous transdiaphragmatic IOUS-guided parenchymal transection can optimize outcomes.

Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit.Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients. Clinical variables, detected mutations, and administered therapies were correlated with overall survival (OS) in a Cox regression model.The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA. Fibroblast growth factor receptor (FGFR; 11%) and IDH mutations (20%) were mostly limited to IHCCA but appeared to be mutually exclusive. In the IHCCA group, TP53 and KRAS mutations were associated significantly with poor OS, whereas FGFR2 mutations were associated with improved OS (P = .001), a younger age at onset, and female sex. IDH1/2 mutations were not prognostic. In a multivariate model, the effects of TP53 and FGFR GAs remained significant (P .05). Patients with FGFR GAs had superior OS with FGFR-targeted therapy versus standard regimens (P = .006). Targeted therapy in IHCCA was associated with a numerical OS improvement (P = .07).This is the largest clinically annotated data set of BTC cases with CGP and indicates the potential of CGP for improving outcomes. CGP should be strongly considered in the management of BTC patients. Cancer 2016;122:3838-3847. © 2016 American Cancer Society.

To compare breath-hold cartesian volumetric interpolated breath-hold examination (cVIBE) and free-breathing radial VIBE (rVIBE) and determine whether rVIBE could replace cVIBE in routine liver magnetic resonance imaging (MRI).In this prospective study, 15 consecutive patients scheduled for routine MRI of the abdomen underwent pre- and post-contrast breath-hold cVIBE imaging (19 s acquisition time) and free-breathing rVIBE imaging (111 s acquisition time) on a 1.5T Siemens scanner. Three radiologists with 2, 4, and 8 years post-fellowship experience in abdominal imaging evaluated all images. The radiologists were blinded to the sequence types, which were presented in a random order for each patient. For each sequence, the radiologists scored the cVIBE and rVIBE images for liver edge sharpness, hepatic vessel clarity, presence of artifacts, lesion conspicuity, fat saturation, and overall image quality using a five-point scale.Compared to rVIBE, cVIBE yielded significantly (P0.001) higher scores for liver edge sharpness (mean score, 3.87 vs 3.37), hepatic-vessel clarity (3.71 vs 3.18), artifacts (3.74 vs 3.06), lesion conspicuity (3.81 vs 3.2), and overall image quality (3.91 vs 3.24). cVIBE and rVIBE did not significantly differ in quality of fat saturation (4.12 vs 4.03, P = 0.17). The inter-observer variability with respect to differences between rVIBE and cVIBE scores was close to zero compared to random error and inter-patient variation. Quality of rVIBE images was rated as acceptable for all parameters.rVIBE cannot replace cVIBE in routine liver MRI. At 1.5T, free-breathing rVIBE yields acceptable, although slightly inferior image quality compared to breath-hold cVIBE.

The purpose of this study is to determine whether focused missed-case conferences can significantly reduce the number of major discrepancies in musculoskeletal imaging studies interpreted by residents on call.A review of major discrepancies in musculoskeletal conventional radiography imaging studies interpreted by radiology residents and fellows on call from July 2008 to July 2009 revealed 31 common and important musculoskeletal injuries missed or misinterpreted at our institution. These missed cases were presented during focused missed-case conferences from July through October 2009. Only residents attended missed-case conferences.Over the 12 months before the missed-case conferences, there were 55 resident major discrepancies and 25 fellow major discrepancies, representing 31 common and important missed musculoskeletal injuries. Over the 12 months after the missed-case conferences, there were 18 resident major discrepancies and 21 fellow major discrepancies involving these injuries. This corresponds to a 67% reduction in the number of resident major discrepancies involving the 31 musculoskeletal injuries covered during the missed-case conferences (chi-square p0.001). The overall major discrepancy rate for all musculoskeletal conventional radiography studies was 1.19% for residents and 1.55% for fellows (not significant) before the missed-case conferences and 0.87% for residents and 1.46% for fellows (p0.05) after the missed-case conferences. During this time, fellows missed more musculoskeletal injuries related to the topics discussed during missed-case conferences (16) compared with residents (8) although fellows read significantly fewer studies overall. This accounted for 0.49% of the 0.59% difference between residents and fellows.Focused missed-case conferences are an effective educational intervention to significantly reduce the number of major discrepancies in radiology resident interpretation of musculoskeletal imaging studies on call.

In radial MR imaging, streaking artifacts contaminating the entire field of view can arise from regions at the outer edges of the prescribed field of view. This can occur even when the Nyquist criterion is satisfied within the desired field of view. These artifacts become exacerbated when parts of the object lie in the superior/inferior regions of the scanner where the gradient strengths become weakened. When multiple coil arrays are used for signal reception, coils at the outer edges can be disabled before data acquisition to reduce the artifact levels. However, as the weakened gradient strengths near the edges often distort the object, causing the signal to become highly concentrated into a small region, the streaks are often not completely removed. Data from certain coils can also be excluded during reconstruction by visually inspecting the individual coil images, but this is impractical for routine use. In this work, a postprocessing method is proposed to automatically identify those coils whose images contain high levels of streaking for subsequent exclusion during reconstruction. The proposed method was demonstrated in vivo dynamic contrast enhanced MRI datasets acquired using a three-dimensional hybrid radial sequence. The results demonstrate that the proposed strategy substantially improves the image quality and show excellent agreement with images reconstructed with manually determined coil selection.

Frequently, the consensus conclusion after quality assurance conferences in radiology is that whatever mistake was made could have been avoided if more prior images or documents had been consulted. It is generally assumed that anything that was not specifically cited in the report had not been consulted. Is it actually safe to assume that an image or document that is not cited was also not consulted? It is this question that this investigation addresses. In this Institutional Review Board-approved study, one observer watched the board-certified radiologists while they interpreted imaging studies and issued reports. He recorded what type of study was being interpreted [either computed tomography, magnetic resonance imaging, or conventional radiography (x-ray)]. He also recorded the number and type of prior imaging studies and documents that were consulted during the interpretation. These observations were then compared with the signed report to determine how many of the consulted imaging studies and documents were cited. Of the 198 previous imaging studies that the radiologists consulted, 116 (58.6%) were cited in a report. Of the 285 documents consulted, 3 (1.1%) were cited in a report. This difference in citation rate was statistically significant ([Formula: see text]). It cannot be safely assumed that an older radiologic image or medical document was not consulted during radiologic interpretation merely because it is not cited in the report. Radiologists often consult more old studies than they cite, and they do not cite the majority of prior documents that they consult.

SummaryWhen performing tasks, humans are thought to adopt task sets that configure moment-to-moment data processing. Recently developed mixed blocked/event-related designs allow task set-related signals to be extracted in fMRI experiments, including activity related to cues that signal the beginning of a task block, “set-maintenance” activity sustained for the duration of a task block, and event-related signals for different trial types. Data were conjointly analyzed from mixed design experiments using ten different tasks and 183 subjects. Dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) showed reliable start-cue and sustained activations across all or nearly all tasks. These regions also carried the most reliable error-related signals in a subset of tasks, suggesting that the regions form a “core” task-set system. Prefrontal regions commonly related to task control carried task-set signals in a smaller subset of tasks and lacked convergence across signal types.

Thequestion of whether pediatric and adult neuroimaging data can be analyzed in a common stereotactic space is a critical issue for developmental neuroscience. Two studies were performed to address this question. In Study 1, high-resolution structural MR brain images of 20 children (7–8 years of age) and 20 young adults (18–30 years of age) were transformed to a common space. Overall brain shape was assessed by tracing the outer boundaries of the brains in three orientations, and more local anatomy was assessed by analysis of portions of 10 selected sulci. Small, but consistent, differences in location and variability were observed in specific locations of the sulcal tracings and outer-boundary sections. In Study 2, a computer simulation was used to assess the extent to which the small anatomical differences observed in Study 1 would produce spurious effects in functional imaging data. Results indicate that, assuming a functional resolution of 5 mm in images averaged across subjects, anatomical differences in either variability or location between children and adults of the magnitude observed in Study 1 would not negatively affect functional image comparisons. We conclude that atlas-transformed brain morphology is relatively consistent between 7- and 8-year-old children and adults at a resolution appropriate to current functional imaging and that the small anatomical differences present do not limit the usefulness of comparing child and adult functional images within a common stereotactic space.

Tumours arising from mesenchymal tissue components such as vascular, fibrous and adipose tissue can manifest in the liver. Although histopathology is often necessary for definitive diagnosis, many of these lesions exhibit characteristic imaging features. The radiologist plays an important role in suggesting the diagnosis, which can direct appropriate immunohistochemical staining at histology. The aim of this review is to present clinical and imaging findings of a spectrum of mesenchymal liver tumours such as haemangioma, epithelioid haemangioendothelioma, lipoma, PEComa, angiosarcoma, inflammatory myofibroblastic tumour, solitary fibrous tumour, leiomyoma, leiomyosarcoma, Kaposi sarcoma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, rhabdomyosarcoma and hepatic metastases. Knowledge of the characteristic features of these tumours will aid in guiding the radiologic diagnosis and appropriate patient management.

432 Background: In clinical trials and clinical practice, tumor response assessment with computed tomography (CT) defines critical end points in patients with metastatic disease treated with systemic agents. Methods to reduce errors and improve efficiency in tumor response assessment could improve patient care. Methods: Eleven readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria using paired baseline and initial post-therapy CT studies from 20 randomly selected patients with metastatic renal cell carcinoma treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard-of-care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error-identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data/image archival. A cross-over design, patient randomization, and two-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. Results: The standard-of-care method was on average associated with one or more errors in 30.5% (6.1/20) of patients while CARE had a 0.0% (0.0/20) error rate (p

Background Cholangiocarcinoma (CCA) is clinically heterogeneous; intra and extrahepatic CCA have diverse clinical presentations. Next generation sequencing (NGS) technology may identify the genetic differences between these entities and identify molecular subgroups for targeted therapeutics. Methods We describe successful NGS-based testing of 75 CCA patients along with the prognostic and therapeutic implications of findings. Mutation profiling was performed using either a) NGS panel of hotspot regions in 46 cancer-related genes using a 318-chip on Ion PGM Sequencer or b) Illumina HiSeq 2000 sequencing platform for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes to an average depth of 1000X. Clinical data was abstracted and correlated with clinical outcome. Patients with targetable mutations were referred to appropriate clinical trials. Results There were significant differences between intrahepatic (n = 55) and extrahepatic CCA (n = 20) in regard to the nature and frequency of the genetic aberrations (GAs). IDH1 and DNA repair gene alterations occurred more frequently in intrahepatic CCA, while ERBB2 GAs occurred in the extrahepatic group. Commonly occurring GAs in intrahepatic CCA were TP53 (35%), KRAS (24%), ARID1A (20%), IDH1 (18%), MCL1 (16%) and PBRM1 (11%). Most frequent GAs in extrahepatic CCA (n = 20) were TP53 (45%), KRAS (40%), ERBB2 (25%), SMAD4 (25%), FBXW7 (15%) and CDKN2A (15%). In intrahepatic CCA, KRAS, TP53 or MAPK/mTOR GAs were significantly associated with a worse prognosis while FGFR GAs correlated with a relatively indolent disease course. IDH1 GAs did not have any prognostic significance. GAs in the chromatin modulating genes, BAP1 and PBRM1 were associated with bone metastases and worse survival in extrahepatic CCA. Radiologic responses and clinical benefit was noted with EGFR, FGFR, C-met, B-RAF and MEK inhibitors. Conclusion There are significant genetic differences between intra and extrahepatic CCA. NGS can potentially identify disease subsets with distinct prognostic and therapeutic implications.

Intramural gastric masses arise in the wall of the stomach (generally within the submucosa or muscularis propria), often with intact overlying mucosa. These tumors are typically mesenchymal in origin and have overlapping radiologic appearances. A combination of features such as location, attenuation, enhancement, and growth pattern may suggest one diagnosis over another. Gastrointestinal stromal tumors (GISTs) account for the majority of intramural tumors and can vary widely in appearance, from small intraluminal lesions to exophytic masses that protrude into the peritoneal cavity, commonly with areas of hemorrhage or necrosis. A well-circumscribed mass measuring −70 to −120 HU is a lipoma. Leiomyomas usually manifest as low-attenuation masses at the gastric cardia. Homogeneous attenuation is a noteworthy characteristic of schwannomas, particularly for larger lesions that might otherwise be mistaken for GISTs. A hypervascular mass in the antrum is a common manifestation of glomus tumors. Hemangiomas are also hypervascular but often manifest in childhood. Inflammatory fibroid polyps usually arise as a polypoid mass in the antrum. Inflammatory myofibroblastic tumors are infiltrative neoplasms with a propensity for local recurrence. Plexiform fibromyxomas are rare, usually antral tumors. Carcinoid tumors are epithelial in origin, but often submucosal in location, and therefore should be distinguished from other intramural lesions. Multiple carcinoid tumors are associated with hypergastrinemia, either in the setting of chronic atrophic gastritis or Zollinger-Ellison syndrome. Sporadic solitary carcinoid tumors not associated with hypergastrinemia have a higher rate of metastasis. Histopathologic analysis, including immunohistochemistry, is usually required for diagnosis of intramural masses. © RSNA, 2013

Preclinical and clinical studies suggest mTOR (mammalian target of rapamycin) inhibitors may have metabolic and antiangiogenic effects, and synergize with epidermal growth factor pathway inhibitors. Therefore, a phase 1/pharmacodynamic trial of everolimus with cetuximab was performed.A total of 29 patients were randomized to a run-in of oral everolimus (30, 50, or 70 mg) or cetuximab (400 mg/m(2) loading, 250 mg/m(2) maintenance) weekly, followed by the combination in this dose-escalation study. Primary endpoints were phase 2 dose and toxicity characterization. [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed as a pharmacodynamic marker of mTOR inhibition, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed as an indicator of tumor perfusion changes, at 3 time points.Everolimus and cetuximab were tolerable at full doses, with an expected toxicity profile. Dose-limiting toxicities in the everolimus 70 mg group included grade 3 skin toxicity in 2 patients, and mucositis in 1 patient. Of 16 patients evaluable for response, 5 had stable disease lasting 4 to 19 months. Mean change in maximum standardized uptake value (SUV(max)) for those treated initially with everolimus was -24% (2% to -54%), and with cetuximab was -5% (-23 to 36%). The K(trans) measured by DCE-MRI did not decrease, regardless of run-in drug.Everolimus and cetuximab can be safely administered at standard doses, and are associated with prolonged disease control. The recommended phase 2 dose of oral weekly everolimus is 70 mg in combination with standard cetuximab. Imaging studies reveal that metabolic inhibition by everolimus alone and in combination with cetuximab predominates over changes in tumor perfusion in this patient population.

e15137 Background: Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular ch...

The development of methods allowing direct comparisons between child and adult neuroimaging data is an important prerequisite for studying the neural bases of cognitive development. Several issues arise when attempting to make such direct comparisons, including the comparability of anatomical localization of functional responses and the magnitude and time course of the hemodynamic responses themselves. Previous results suggest that, after transformation into a common stereotactic space, anatomical differences between children (ages 7 and 8) and adults are small relative to the resolution of fMRI data. Here, we investigate whether time courses (BOLD responses) and locations of functional activation foci show similarities as well. Event-related fMRI was performed on 16 children (ages 7 and 8) and 16 adults, who pressed buttons in response to a visual stimulus. After transforming images into Talairach space, the coordinates of four consistent activations in each hemisphere were determined for each subject: two foci in the sensorimotor cortex, one focus in the visual cortex, and one focus in the supplementary motor area (eight activations in total). In seven foci, time courses were similar between children and adults, and peak amplitudes of time courses were comparable in all eight foci. There were negligible between-group differences in location of all foci. Variability of activation location was statistically similar in the two groups. In voxelwise group comparison images, minimal differences were found between children and adults in visual and motor cortex regions. The small differences in time courses and locations of activation foci between child and adult brains validate the feasibility of direct statistical comparison of these groups within a common space.