John R. Leyendecker

Diagnosis of Focal Nodular Hyperplasia With MRI: Multicenter Retrospective Study Comparing Gadobenate Dimeglumine to Gadoxetate Disodium

OBJECTIVE The purpose of this article is to report the results from a multicenter retrospective MRI study comparing gadobenate dimeglumine and gadoxetate disodium for diagnosis of hepatic focal nodular hyperplasia (FNH). MATERIALS AND METHODS Thirty patients (28 women and two men; mean age, 37.1 years) with hepatic FNH who underwent both gadobenate dimeglumine- and gadoxetate disodium-enhanced MRI at 1.5 T were assessed. MRI was performed during the arterial, portal venous, late venous, and hepatobiliary contrast-enhanced phases (10 and 20 minutes or 1-3 hours after contrast administration, respectively, for gadoxetate disodium and gadobenate dimeglumine). Qualitative (lesion conspicuity score) and quantitative (lesion signal intensity [SI] ratio and lesion contrast ratio) assessments were performed. RESULTS In 30 patients, 51 FNHs were assessed (mean size 3.1 ± 1.5 cm). There was equivalent qualitative lesion conspicuity in the arterial phase between the two contrast agents and higher qualitative lesion conspicuity and SI ratio in the hepatobiliary phase with gadoxetate disodium (p < 0.002). Lesion contrast ratio was significantly higher in the arterial and late venous phases with gadobenate dimeglumine (p < 0.009), with no difference in the portal venous and hepatobiliary phases between the two contrast agents (p > 0.22). CONCLUSION These results indicate an advantage for gadobenate dimeglumine for detection of FNH at the dynamic phase and for gadoxetate disodium at the hepatobiliary phase. However, the equivalent or better qualitative lesion conspicuity coupled with the ability to obtain a comprehensive evaluation of the liver within a standard 30-minute imaging window suggests that gadoxetate disodium may be a better choice for diagnosis of FNH.

Complete Pancreatic Encasement of the Portal Vein (Circumportal Pancreas) : Imaging Findings and Implications of a Rare Pancreatic Anomaly

Computed tomography and magnetic resonance imaging findings in 4 patients with complete pancreatic encasement of the portal vein are presented, with emphasis on the use of multiplanar reconstructions in demonstrating this anomaly.

In-phase signal intensity loss in solid renal masses on dual-echo gradient-echo MRI: association with malignancy and pathologic classification.

OBJECTIVE The purposes of this study were to determine the prevalence of in-phase signal intensity loss on dual-echo gradient-echo MRI in solid renal masses using visual and quantitative techniques and to test for any association between in-phase signal intensity loss and pathologic classification. MATERIALS AND METHODS The renal MRI studies of 177 patients (192 solid masses consisting of 166 renal cell carcinomas [RCCs], four malignant non-RCCs, and 22 benign tumors) were qualitatively reviewed by two blinded readers for visual evidence of relative in-phase signal intensity loss. For lesions without visual evidence, whole-lesion ROIs were used to attempt quantification of subtle signal intensity loss between opposed- and in-phase images (signal intensity loss index). RESULTS Visual in-phase signal intensity loss was noted in 18% of clear cell RCC, 42% of papillary RCC, and no benign lesions. There was significant correlation between malignancy and visual signal intensity loss (Fisher exact test, p = 0.0092). Visual signal intensity loss was predictive of papillary RCC over clear cell RCC (odds ratio, 5.79; p = 0.0002) in logistic regression analysis of all RCCs, controlling for size. Quantitative assessment of remaining lesions provided no additional diagnostic benefit. CONCLUSION Visible in-phase signal intensity loss is relatively common within solid renal masses and was associated with RCC and particularly papillary RCC (among all RCCs) in our population. Quantitative analysis in lesions without visible signal intensity loss was not predictive of RCC. Further work should be performed to validate the usefulness of this additional imaging parameter to help characterize renal masses and to determine the impact of this finding on imaging techniques potentially sensitive to susceptibility effects.

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial

BACKGROUND Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. METHODS In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2, leucovorin at 400 mg/m2, irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. FINDINGS Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m2. The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m2, and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. INTERPRETATION A maximum tolerated dose of CPI-613 was established at 500 mg/m2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. FUNDING Comprehensive Cancer Center of Wake Forest Baptist Medical Center.Background Pancreatic cancer statistics are dismal, with a five-year survival of less than 10%, and over 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma, including aerobic glycolysis, oxidative phosphorylation, glutaminolysis, lipogenesis and lipolysis, autophagic status, and anti-oxidative stress. CPI-613 is a novel anti-cancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumor cells, causing changes in mitochondrial enzyme activities and redox status which lead to apoptosis, necrosis and autophagy of tumor cells. Methods This is a phase 1 study to determine the maximum-tolerated dose (MTD) of CPI-613 when used in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2 and irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2 bolus and 2400 mg/m2 over 46 h) in combination with CPI-613 in patients with newly diagnosed metastatic pancreatic adenocarcinoma with good bone marrow, liver and kidney function and good performance status (NCT01835041 – closed to recruitment). A two-stage dose-escalation scheme (single patient and traditional 3+3 design) was applied. In the single patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m2/day; the dose level was then escalated by doubling the previous dose if there was no toxicity greater than Grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxicity attributed as probably or definitely related to CPI-613 was ≥ Grade 2. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as used in the last cohort of the single patient dose-escalation stage. Secondary objectives were safety, preliminary efficacy, and tissue collection for future analyses. Response rates, progression-free survival and overall survival data were assessed in the patients treated at the MTD. Findings Twenty patients were enrolled April 22, 2013 – January 8, 2016. The MTD of CPI-613 was 500 mg/m2. The median number of treatment cycles administered at the MTD was 11 (interquartile range, 4–19). Two patients enrolled at a higher dose (1000 mg/m2) both experienced a DLT (dose limiting toxicity). There were 2 unexpected serious adverse events (SAEs), both for the first patient enrolled: 1) possible leaching due to infusion of CPI-613 via non-PVC tubing, and 2) the patient re- accessed her port at home after accidental de-access. Neither incident resulted in a negative clinical outcome. Expected SAEs were: thrombocytopenia, anemia and lymphopenia (all for Patient #2, with anemia and lymphopenia being a DLT); hyperglycemia (Patient #7); hypokalemia, hypoalbuminemia and sepsis (Patient #11); and neutropenia (Patient #20). There was no grade 5 toxicity. For the 18 patients treated at the MTD, the most common Grade 3–4 toxicities were hypokalemia (6/18, 33%), diarrhea (5/18, 28%) and abdominal pain (4/18, 22%). Sensorial neuropathy (17/18, 94%) was managed with dose de-escalation or discontinuation per standard of care. None of the patients experienced grade 4 or 5 neuropathy. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Among the 18 patients treated with the MTD, there were 3 patients with a complete response (CR), 1 with a non-CR/non-progressive disease, 7 with a partial response (PR), 3 with stable disease, and 4 with PD. The partial + complete response rate was 61% (11/18). Interpretation The treatment was well tolerated and all end points were met. The intriguing signal of efficacy will require validation in a phase 2 study. Funding Comprehensive Cancer Center of Wake Forest Baptist Medical Center

Thermal ablation: update and technique at a high-volume institution

In the era of nephron-sparing surgery for small renal tumors, thermal ablation is gaining popularity. Both cryoablation and radiofrequency ablation have well-demonstrated short-term oncologic efficacy and safety. This article shares the current literature and the radiofrequency ablation technique at a high-volume institution. Cases are presented that illustrate solutions to obstacles frequently encountered during percutaneous ablation of renal masses.

Differentiation of renal neoplasms from high-density cysts: use of attenuation changes between the corticomedullary and nephrographic phases of computed tomography.

Purpose: The current study evaluated attenuation changes for proven renal neoplasms between the corticomedullary and the nephrographic phases of a contrast-enhanced computed tomographic (CT) scan as a possible means for differentiating these tumors from the cysts of the kidney when high-density renal masses are detected on a CT scan that does not include a noncontrast baseline. Methods: We retrospectively reviewed the CT scans performed on 20 patients with 21 biopsy-proven renal neoplasms, which had been done using standard contrast-enhanced computed tomography only. Attenuation values for the 21 renal neoplasms and for 23 simple cysts, used as an internal control, were measured and recorded from the 2 phases of enhancement. The difference in attenuation between the 2 phases of enhancement for each mass was calculated. Data for the neoplasms and cysts were compared with published data for enhancement changes for proven high-density renal cysts. Results: The mean absolute value change in attenuation between the corticomedullary and the nephrographic phases for renal neoplasms was 22 Hounsfield units (HU) (range, 1.0-48 HU) and 1 HU (range, 0.1-3.3 HU) for simple cysts. Only one renal neoplasm (5%) changed to less than 10 HU. Conclusions: Almost all renal neoplasms studied had an attenuation change of more than 10 HU, either increased or decreased, between 2phases of a contrast-enhanced CT scan separated by 50 seconds. The results suggest that if the attenuation of a renal tumor changes by more than 10 HU between phases of a contrast-enhanced computed tomography, then the diagnosis of renal neoplasm is very likely. High-attenuation renal masses which change less than 10 HU between the corticomedullary and tubular phases are most likely high-density cysts, but neoplasm is possible.

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Identify Clear Cell Renal Cell Carcinoma in cT1a Renal Masses

Purpose: The detection of small renal masses is increasing with the use of cross‐sectional imaging, although many incidental lesions have negligible metastatic potential. Among malignant masses clear cell renal cell carcinoma is the most prevalent and aggressive subtype. A method to identify such histology would aid in risk stratification. Our goal was to evaluate a likelihood scale for multiparametric magnetic resonance imaging in the diagnosis of clear cell histology. Materials and Methods: We retrospectively reviewed the records of patients with cT1a masses who underwent magnetic resonance imaging and partial or radical nephrectomy from December 2011 to July 2015. Seven radiologists with different levels of experience who were blinded to final pathology findings independently reviewed studies based on a predefined algorithm. They applied a clear cell likelihood score, including 1—definitely not, 2—probably not, 3—equivocal, 4—probably and 5—definitely. Binary classification was used to determine the accuracy of clear cell vs all other histologies. Interobserver agreement was calculated with the weighted &kgr; statistic. Results: A total of 110 patients with 121 masses were identified. Mean tumor size was 2.4 cm and 50% of the lesions were clear cell. Defining clear cell as scores of 4 or greater demonstrated 78% sensitivity and 80% specificity while scores of 3 or greater showed 95% sensitivity and 58% specificity. Interobserver agreement was moderate to good with a mean &kgr; of 0.53. Conclusions: A clear cell likelihood score used with magnetic resonance imaging can reasonably identify clear cell histology in small renal masses and may decrease the number of diagnostic renal mass biopsies. Standardization of imaging protocols and reporting criteria is needed to improve interobserver reliability.

Practical Approach to MRI of Female Pelvic Masses

OBJECTIVE Female pelvic masses have a broad differential diagnosis, including benign and malignant neoplasms and nonneoplastic entities. CONCLUSION By using a systematic approach to the evaluation of a complex pelvic mass, including incorporating the clinical and surgical history, and by using multiparametric MRI to identify the anatomic origin, morphologic features, and tissue composition of a mass, a short meaningful differential diagnosis or definitive diagnosis can often be established.

Diagnostic performance and interreader agreement of a standardized MR imaging approach in the prediction of small renal mass histology

Purpose To assess the diagnostic performance and interreader agreement of a standardized diagnostic algorithm in determining the histologic type of small (≤4 cm) renal masses (SRMs) with multiparametric magnetic resonance (MR) imaging. Materials and Methods This single-center retrospective HIPAA-compliant institutional review board-approved study included 103 patients with 109 SRMs resected between December 2011 and July 2015. The requirement for informed consent was waived. Presurgical renal MR images were reviewed by seven radiologists with diverse experience. Eleven MR imaging features were assessed, and a standardized diagnostic algorithm was used to determine the most likely histologic diagnosis, which was compared with histopathology results after surgery. Interreader variability was tested with the Cohen κ statistic. Regression models using MR imaging features were used to predict the histopathologic diagnosis with 5% significance level. Results Clear cell renal cell carcinoma (RCC) and papillary RCC were diagnosed, with sensitivities of 85% (47 of 55) and 80% (20 of 25), respectively, and specificities of 76% (41 of 54) and 94% (79 of 84), respectively. Interreader agreement was moderate to substantial (clear cell RCC, κ = 0.58; papillary RCC, κ = 0.73). Signal intensity (SI) of the lesion on T2-weighted MR images and degree of contrast enhancement (CE) during the corticomedullary phase were independent predictors of clear cell RCC (SI odds ratio [OR]: 3.19; 95% confidence interval [CI]: 1.4, 7.1; P = .003; CE OR, 4.45; 95% CI: 1.8, 10.8; P < .001) and papillary RCC (CE OR, 0.053; 95% CI: 0.02, 0.2; P < .001), and both had substantial interreader agreement (SI, κ = 0.69; CE, κ = 0.71). Poorer performance was observed for chromophobe histology, oncocytomas, and minimal fat angiomyolipomas, (sensitivity range, 14%-67%; specificity range, 97%-99%), with fair to moderate interreader agreement (κ range = 0.23-0.43). Segmental enhancement inversion was an independent predictor of oncocytomas (OR, 16.21; 95% CI: 1.0, 275.4; P = .049), with moderate interreader agreement (κ = 0.49). Conclusion The proposed standardized MR imaging-based diagnostic algorithm had diagnostic accuracy of 81% (88 of 109) and 91% (99 of 109) in the diagnosis of clear cell RCC and papillary RCC, respectively, while achieving moderate to substantial interreader agreement among seven radiologists.

MRI of the pelvis: a guide to incidental findings for musculoskeletal radiologists.

Patients undergoing magnetic resonance imaging (MRI) of the pelvis for presumed musculoskeletal disease are commonly found to have abnormal imaging findings in the incidentally imaged pelvic viscera. Such incidental findings can be problematic for the musculoskeletal imager, both in terms of assigning clinical significance and determining the appropriate workup for a given abnormality. In this article we discuss the normal MRI appearance of the various pelvic organ systems as well as normal variants, emphasizing those that can mimic pathological processes. We then discuss the MRI appearance of common pathological entities encountered in these organ systems and the key imaging findings that should warrant a recommendation for further radiologic and/or clinical evaluation.