Non-contrast short MRI surveillance for HCC screening: the study protocol of the SMS-HCC prospective multicenter study.

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.

18 F-FDG PET/MRI for restaging esophageal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose ( 18 F-FDG) PET/MRI may potentially improve tumor detection after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: This was a prospective, single-center feasibility study. At 6-12 weeks after nCRT, patients underwent standard 18 F-FDG PET/computed tomography (CT) followed by PET/MRI, and completed a questionnaire to evaluate burden. Two teams of readers either assessed the 18 F-FDG PET/CT or the 18 F-FDG PET/MRI first; the other scan was assessed 1 month later. Maximum standardized uptake value corrected for lean body mass (SUL max ) and mean apparent diffusion coefficient (ADC mean ) were measured at the primary tumor location. Histopathology of the surgical resection specimen served as the reference standard for diagnostic accuracy calculations. When patients had a clinically complete response and continued active surveillance, response evaluations until 9 months after nCRT served as a proxy for ypT and ypN (i.e. 'ycT' and 'ycN'). RESULTS: In the 21 included patients [median age 70 (IQR 62-75), 16 males], disease recurrence was found in the primary tumor in 14 (67%) patients (of whom one ypM+, detected on both scans) and in locoregional lymph nodes in six patients (29%). Accuracy (team 1/team 2) to detect yp/ycT+ with 18 F-FDG PET/MRI vs. 18 F-FDG PET/CT was 38/57% vs. 76/61%. For ypN+, accuracy was 63/53% vs. 63/42%, resp. Neither SUL max (both scans) nor ADC mean were discriminatory for yp/ycT+ . Fourteen of 21 (67%) patients were willing to undergo a similar 18 F-FDG PET/MRI examination in the future. CONCLUSION: 18 F-FDG PET/MRI currently performs comparably to 18 F-FDG PET/CT. Improvements in the scanning protocol, increasing reader experience and performing serial scans might contribute to enhancing the accuracy of tumor detection after nCRT using 18 F-FDG PET/MRI. TRIAL REGISTRATION: Netherlands Trial Register NL9352.

Detection of metastases using circulating tumour DNA in uveal melanoma.

BACKGROUND: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3-12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. METHODS: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. RESULTS: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7-151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. CONCLUSIONS: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.

Endoscopic ultrasound in patients with resectable perihilar cholangiocarcinoma: impact on clinical decision-making.

Background and study aims Accurate assessment of the lymph node (LN) status is crucial in resectable perihilar cholangiocarcinoma (pCCA) to prevent major surgery in patients with extraregional metastatic LNs (MLNs). This study investigates the added value of preoperative endoscopic ultrasound (EUS) with or without tissue acquisition (TA) for the detection of MLNs in patients with resectable pCCA. Patients and methods In this retrospective, multicenter cohort study, patients with potentially resectable pCCA who underwent EUS preoperatively between 2010-2020, were included. The clinical impact of EUS-TA was defined as the percentage of patients who did not undergo surgical resection due to MLNs found with EUS-TA. Findings of cross-sectional imaging were compared with EUS-TA findings and surgery. Results EUS was performed on 141 patients, of whom 107 (76 %) had suspicious LNs on cross-sectional imaging. Surgical exploration was prevented in 20 patients (14 %) because EUS-TA detected MLNs, of which 17 (85 %) were extraregional. Finally, 74 patients (52 %) underwent surgical exploration followed by complete resection in 40 (28 %). MLNs were identified at definitive pathology in 24 (33 %) patients, of which 9 (38 %) were extraregional and 15 (63 %) regional. Conclusions EUS-TA may be of value in patients with potentially resectable pCCA based on preoperative cross-sectional imaging, regardless of lymphadenopathy at cross-sectional imaging. A prospective study in which a comprehensive EUS investigation with LN assessment and EUS-TA of LNs is performed routinely should confirm this promise.

Stromal vascular fraction with platelet-rich plasma injection during surgery is feasible and safe in treatment-refractory perianal fistulising Crohn's disease: A pilot study.

BACKGROUND: An unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose-derived cells has shown promising results. AIMS: To assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in patients with pCD. METHODS: Patients ≥ 18 years with pCD were included and underwent fistula curettage, SVF with PRP injection, and closure of the internal opening. The primary endpoint was safety at 12 months. The secondary outcomes were complete radiological healing at 3 months (absence of fluid-containing tracts on MRI) and partial and complete clinical response at 3 and 12 months (closure of ≥1, respectively, all treated external opening(s)). RESULTS: Twenty-five patients were included (35 [IQR 25-40] years; 14 [56%] female); median CD duration 4 [IQR 2-8] years. Twenty-four (95%) patients had previously undergone fistula surgery. No adverse events were encountered at lipoharvesting sites. Two (8%) patients were readmitted to hospital and six (24%) underwent unplanned re-interventions. Post-operative MRI (n = 24) showed complete radiological healing in nine (37.5%) patients. Partial clinical response was present in 48% (12/25) at 3 months and in 68% (17/25) at 12 months, and complete clinical closure in five (20%) patients at 3 months and in 10 (40%) patients at 12 months. CONCLUSION: Injection with autologous SVF with PRP is feasible and safe in patients with treatment-refractory pCD. Early complete radiological healing was observed in more than one-third of patients, and clinical response in two-thirds of patients at 12 months.

Potential of a Non-Contrast-Enhanced Abbreviated MRI Screening Protocol (NC-AMRI) in High-Risk Patients under Surveillance for HCC.

PURPOSE: To evaluate NC-AMRI for the detection of HCC in high-risk patients. METHODS: Patients who underwent yearly contrast-enhanced MRI (i.e., full MRI protocol) of the liver were included retrospectively. For all patients, the sequences that constitute the NC-AMRI protocol, namely diffusion-weighted imaging (DWI), T2-weighted (T2W) imaging with fat saturation, and T1-weighted (T1W) in-phase and opposed-phase imaging, were extracted, anonymized, and uploaded to a separate research server and reviewed independently by three radiologists with different levels of experience. Reader I and III held a mutual training session. Levels of suspicion of HCC per patient were compared and the sensitivity, specificity, and area under the curve (AUC) using the Mann-Whitney U test were calculated. The reference standard was a final diagnosis based on full liver MRI and clinical follow-up information. RESULTS: Two-hundred-and-fifteen patients were included, 36 (16.7%) had HCC and 179 (83.3%) did not. The level of agreement between readers was reasonable to good and concordant with the level of expertise and participation in a mutual training session. Receiver operating characteristics (ROC) analysis showed relatively high AUC values (range 0.89-0.94). Double reading showed increased sensitivity of 97.2% and specificity of 87.2% compared with individual results (sensitivity 80.1%-91.7%-97.2%; specificity 91.1%-72.1%-82.1%). Only one HCC (2.8%) was missed by all readers. CONCLUSION: NC-AMRI presents a good potential surveillance imaging tool for the detection of HCC in high-risk patients. The best results are achieved with two observers after a mutual training session.

Differential Diagnosis and Molecular Stratification of Gastrointestinal Stromal Tumors on CT Images Using a Radiomics Approach.

Treatment planning of gastrointestinal stromal tumors (GISTs) includes distinguishing GISTs from other intra-abdominal tumors and GISTs' molecular analysis. The aim of this study was to evaluate radiomics for distinguishing GISTs from other intra-abdominal tumors, and in GISTs, predict the c-KIT, PDGFRA, BRAF mutational status, and mitotic index (MI). Patients diagnosed at the Erasmus MC between 2004 and 2017, with GIST or non-GIST intra-abdominal tumors and a contrast-enhanced venous-phase CT, were retrospectively included. Tumors were segmented, from which 564 image features were extracted. Prediction models were constructed using a combination of machine learning approaches. The evaluation was performed in a 100 × random-split cross-validation. Model performance was compared to that of three radiologists. One hundred twenty-five GISTs and 122 non-GISTs were included. The GIST vs. non-GIST radiomics model had a mean area under the curve (AUC) of 0.77. Three radiologists had an AUC of 0.69, 0.76, and 0.84, respectively. The radiomics model had an AUC of 0.52 for c-KIT, 0.56 for c-KIT exon 11, and 0.52 for the MI. The numbers of PDGFRA, BRAF, and other c-KIT mutations were too low for analysis. Our radiomics model was able to distinguish GISTs from non-GISTs with a performance similar to three radiologists, but less observer dependent. Therefore, it may aid in the early diagnosis of GIST, facilitating rapid referral to specialized treatment centers. As the model was not able to predict any genetic or molecular features, it cannot aid in treatment planning yet.

Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status.

This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging. Hepatic metastatic patterns were classified by counting the number of metastases found in the liver. Miliary metastatic pattern (innumerable small metastases in the entire liver) was analyzed separately. Mutation status was determined in 85 patients. Median disease-free survival (DFS) and survival with metastases differed significantly between each of the metastatic patterns (respectively, p = 0.009, p < 0.001), both in favor of patients with less hepatic metastases. The mutation status of the primary tumor was not correlated with any hepatic tumor profiles (p = 0.296). Of the patients who had a solitary metastasis (n = 18), 11 originated from a primary BAP1-mutated tumors and one from a primary SF3B1-mutated tumor. Of the patients who had a miliary metastasis pattern (n = 24), 17 had a primary BAP1-mutated tumor and two had a primary SF3B1-mutated tumor. Chromosome 8p loss was significantly more in patients with more metastases (p = 0.045). Moreover, the primary UMs of patients with miliary metastases harbored more chromosome 8p and 1p loss, compared to patients with single solitary metastasis (p = 0.035 and p = 0.026, respectively). In conclusion, our study shows that there is an inverse correlation of the number of metastasis with the DFS and metastasized survival, indicating separate growth patterns. We also revealed that the number and type of metastases is irrelevant to the prognostic mutation status of the tumor, showing that both BAP1- and SF3B1-mutated UM can result in solitary and miliary metastases, indicating that other processes lay ground to the different metastatic patterns.

Calcification of the Aorta-Iliac Trajectory as a Risk Factor for Anastomotic Leakage in Colorectal Surgery: Individual Patient Data Meta-Analysis and Systematic Review.

OBJECTIVE: The purpose of this review is to evaluate the relevance of vascular calcification as a potential risk factor for anastomotic leakage in colorectal surgery. METHOD: The Embase, Medline, PubMed, and Cochrane databases and Google Scholar were systematically searched. Studies that assessed calcification of the aorta-iliac trajectory in patients who underwent colorectal surgery were included. An independent patient data meta-analysis was performed as follows: based on the heterogeneity of the study population, a "random-effects model" or "fixed-effects model" was used to perform a multivariable logistic regression and calculate pooled Odds Ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the Q-test and I2-test. RESULTS: From a total of 457 articles retrieved, eight fell within the scope of the review, with a total of 2010 patients. Anastomotic leakage was found at a mean rate of 11.1% (SD 4.9%). In these eight studies, four different calcification scoring methods were used, which made a single structured meta-analysis not feasible. Therefore, an independent patient data meta-analysis on the most frequently used calcification scoring method was performed, including three studies with a total of 396 patients. After multivariable analyses, no significant association was found between anastomotic leakage and the amount of calcification in the aorta-iliac trajectory. The remaining three scoring methods were evaluated. In four of the five studies, vascular calcification was associated with anastomotic leakage after colorectal surgery. CONCLUSION: In contrast to previous studies, an individual patient data meta-analysis found no association between calcification and anastomotic leakage in colorectal surgery after multivariable analysis that considered a single calcification measurement method. In addition, this study demonstrated several scoring methods for arterial calcification and the need for a standardized technique. Therefore, the authors would recommend prospective studies using a calcification scoring method that includes grade of stenosis due to its potential to preoperatively improve perfusion by endovascular treatment.

Predicting symptomatic mesenteric mass in small intestinal neuroendocrine tumors using radiomics.

Metastatic mesenteric masses of small intestinal neuroendocrine tumors (SI-NETs) are known to often cause intestinal complications. The aim of this study was to identify patients at risk to develop these complications based on routinely acquired CT scans using a standardized set of clinical criteria and radiomics. Retrospectively, CT scans of SI-NET patients with a mesenteric mass were included and systematically evaluated by five clinicians. For the radiomics approach, 1128 features were extracted from segmentations of the mesenteric mass and mesentery, after which radiomics models were created using a combination of machine learning approaches. The performances were compared to a multidisciplinary tumor board (MTB). The dataset included 68 patients (32 asymptomatic, 36 symptomatic). The clinicians had AUCs between 0.62 and 0.85 and showed poor agreement. The best radiomics model had a mean AUC of 0.77. The MTB had a sensitivity of 0.64 and specificity of 0.68. We conclude that systematic clinical evaluation of SI-NETs to predict intestinal complications had a similar performance than an expert MTB, but poor inter-observer agreement. Radiomics showed a similar performance and is objective, and thus is a promising tool to correctly identify these patients. However, further validation is needed before the transition to clinical practice.

The yield of chest computed tomography in patients with locally advanced pancreatic cancer.

OBJECTIVE: To evaluate the incidence of pulmonary metastases on chest computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: All patients diagnosed with LAPC in a single tertiary center (Erasmus MC) between October 2011 and December 2017 were reviewed. The staging chest CT scan and follow-up chest CT scans were evaluated. Pulmonary nodules were divided into three categories: apparent benign, too small to characterize, and apparent malignant. RESULTS: In 124 consecutive patients diagnosed with LAPC, 119 (96%) patients underwent a staging chest CT scan at the initial presentation. In 88 (74%) patients no pulmonary nodules were found; in 16 (13%) patients an apparent benign pulmonary nodule was found, and in 15 (13%) patients a pulmonary nodule too small to characterize was found. Follow-up chest CT scan(s) were performed in 111 (93%) patients. In one patient with either no pulmonary nodule or an apparent benign pulmonary nodule at initial staging, an apparent malignant pulmonary nodule was found on a follow-up chest CT scan. However, a biopsy of the nodule was inconclusive. Of 15 patients in whom a pulmonary nodule too small to characterize was found at staging, 12 (80%) patients underwent a follow-up CT scan; in 4 (33%) of these patients, an apparent malignant pulmonary nodule was found. CONCLUSION: In patients with LAPC in whom at diagnosis a chest CT scan revealed either no pulmonary nodules or apparent benign pulmonary nodules, routine follow-up chest CT scans is not recommended. Patients with pulmonary nodules too small to characterize are at risk to develop apparent malignant pulmonary nodules during follow-up.

Response to Letter: Intrapatient Comparison of the Hepatobiliary Phase of Gd-BOPTA and Gd-EOB-DTPA in the Differentiation of HCA From FNH.

LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1281-1282.

Performance of Contrast-Enhanced Sonography Versus MRI With a Liver-Specific Contrast Agent for Diagnosis of Hepatocellular Adenoma and Focal Nodular Hyperplasia.

OBJECTIVE. The purpose of this article is to compare contrast-enhanced sonography (CEUS) with sulfur hexafluoride with MRI with the liver-specific contrast agent gadobenate dimeglumine in the diagnosis of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) in a cohort of consecutive patients. MATERIALS AND METHODS. Patients referred to a tertiary center for hepatobiliary disease who had suspected HCA or FNH on MRI performed with an extracellular gadolinium-based contrast agent underwent a prospective workup including CEUS and MRI with a liver-specific contrast agent. Diagnosis was definite when the findings of CEUS and MRI with a liver-specific contrast agent were concordant; histopathologic examination (HPE) was performed for cases with discordant findings. Descriptive statistics and the association between categoric variables were presented as numbers and percentages and were assessed using the Fisher exact test. The primary analysis was patient based. Sensitivity, specificity, and AUC and predictive values for the diagnosis of HCA and FNH were calculated separately for CEUS and MRI with a liver-specific contrast agent. RESULTS. A total of 181 patients were selected for the first analysis. Findings from CEUS and MRI with a liver-specific contrast agent were concordant for 132 patients (73%) and discordant for 49 (27%). HPE was performed for 26 of the 49 patients with discordant findings (53%), with findings indeterminate for two of these patients, the findings of MRI with a liver-specific contrast agent correct for 21 of the remaining 24 patients (87.5%), and the findings of CEUS correct for three of these 24 patients (12.5%) (p < 0.05). For further analysis, 156 patients with concordant findings or HPE-proven cases were included. For CEUS, the sensitivity and specificity for the diagnosis of HCA and FNH were 85% and 87%, respectively; the ROC AUC value was 0.856; and the positive predictive value and negative predictive value were 79% and 90%, respectively. For MRI with a liver-specific contrast agent, the sensitivity and specificity were 95% each, the ROC AUC value was 0.949, and the positive predictive value and negative predictive value were 92% and 97%, respectively, for the diagnosis of HCA and FNH. CONCLUSION. The findings of CEUS and MRI with a liver-specific contrast agent showed fair agreement for the diagnosis of HCA and FNH. MRI with a liver-specific contrast agent is diagnostically correct significantly more often than CEUS in cases with discordant findings that are HPE proven.

Hepatic angiomyolipoma: an international multicenter analysis on diagnosis, management and outcome.

BACKGROUND: Hepatic angiomyolipoma (HAML) may easily be misdiagnosed as a malignancy. The study aim was to assess diagnostic dilemmas, clinical management and outcome of this rare tumor. METHODS: This retrospective international multicenter study included all patients with pathologically proven HAML diagnosed between 1997 and 2017. Data on patient characteristics, diagnostic work-up, management and follow-up were analyzed. RESULTS: Thirty-eight patients were included, 32 female. Median age was 56yrs (i.q.r. 43-64) and median HAML-diameter was 57.5 mm (i.q.r. 38.5-95.3). Thirty patients had undergone CT and 27/38 MRI of the liver, diagnostic biopsy was performed in 19/38. Initial diagnosis was incorrect in 15/38 patients, of which 13 were thought to have malignancy. In 84% biopsy resulted in a correct preoperative diagnosis. Twenty-nine patients were managed with surgical resection, 4/38 with surveillance and 3/38 with liver transplantation. Recurrence after resection occurred in two cases. No HAML related deaths or progression to malignancy were documented. CONCLUSION: HAML diagnosis proved problematic even in hepatobiliary expertise centers. Biopsy is indicated and may provide valuable additional information when HAML diagnosis is considered on cross-sectional imaging, especially when surgical resection imposes a risk of complications. Conservative management with regular imaging follow-up might be justified when biopsy confirms (classic type) HAML.

Intrapatient Comparison of the Hepatobiliary Phase of Gd-BOPTA and Gd-EOB-DTPA in the Differentiation of Hepatocellular Adenoma From Focal Nodular Hyperplasia.

BACKGROUND: Current imaging guidelines do not specify the preferred hepatobiliary contrast agent when differentiating hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH) on MRI. PURPOSE: To analyze intrapatient differences in the hepatobiliary phase (HBP) after use of both gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI to differentiate HCA from FNH. STUDY TYPE: Retrospective. POPULATION: Patients who underwent both Gd-BOPTA and Gd-EOB-DTPA-enhanced MRI, including 33 patients with 82 lesions (67 HCA; 15 FNH), with a step-down reference standard of pathology, 20% regression, identical appearance to earlier biopsied lesions, and stringent imaging findings. FIELD STRENGTH/SEQUENCE: 1.5T and 3T HBP of Gd-BOPTA and Gd-EOB-DTPA-enhanced MRI, precontrast fat-suppressed T1 -weighted sequence. ASSESSMENT: Signal intensities relative to the surrounding liver in the HBP were assessed by two observers. STATISTICAL TESTS: Sensitivity and specificity of HCA diagnosis were calculated for both contrast agents. Interobserver agreement was evaluated using Cohen's kappa; differences in degree of certainty for scoring a lesion were calculated by means of the Wilcoxon signed rank test. Differences in signal intensity between Gd-BOPTA and Gd-EOB-DTPA were calculated using McNemar's test. RESULTS: Almost perfect agreement was found between observers for scored signal intensities with both contrast agents. In 30 of the 82 lesions (37%) a difference was observed between contrast agents in the HBP, with Gd-EOB-DTPA proving correct in all but one of the discordant lesions. When distinguishing HCA from FNH, Gd-BOPTA showed a sensitivity of 46% (31/67) and a specificity of 87% (13/15), while the sensitivity and specificity of Gd-EOB-DTPA was 85% (57/67) and 100% (15/15), respectively. A risk of misclassifying HCA as FNH typically occurs for Gd-BOPTA when lesions are intrinsically hyperintense (P < 0.005). DATA CONCLUSION: The HBP of Gd-EOB-DTPA shows superior accuracy in ruling out HCA in comparison with Gd-BOPTA, especially when the lesion is intrinsically hyperintense on T1 -weighted imaging. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:700-710.

Validation of Ultrasonographic Kidney Volume Measurements: A Reliable Imaging Modality.

OBJECTIVES: To investigate the kidney selection procedure before donation to maximize donor safety, we investigated whether ultrasonographic measurements of kidney volume are comparable with computed tomography measurements. Predonation volume and increases in kidney size may be important indicators of renal function after donation and subsequent loss of function. MATERIALS AND METHODS: Consecutive donors with predonation computed tomography scans were approached preoperatively for additional ultrasonographic examinations. Measurements were independently performed by 2 ultrasonographers and considered accurate when the mean differences between both examiners for length, width, and thickness of the kidneys were < 5 mm. Ultrasonographic volumes were calculated with the ellipsoid equation (length × width × thickness × π/6) and an adjusted equation (length × width × thickness × 0.674), and computed tomography volumes were calculated with the voxel count method, which is considered the criterion standard. RESULTS: For this study (Dutch Trial Register NTR3795), 100 kidneys were measured. The mean differences between examiner 1 and 2 for similar ultrasonography measurements were < 5 mm. The ellipsoid equation underestimated the volume for examiner 1 by 16.9% and for examiner 2 by 14.8%, whereas the adjusted equation overestimated the volume by 6.8% and 9.5% respectively. The correlation between computed tomography and ultrasonographic volume with the adjusted equation was strong for both examiner 1 (r = 0.76; P < .001) and examiner 2 (r = 0.80; P < .001). CONCLUSIONS: Ultrasonographic measurements of kidney volume are comparable with computed tomography measurements. Therefore, ultrasonography is a reliable modality for living kidney donor follow-up monitoring of kidney size adaption after donation.

Characteristics of Prostate Cancer Found at Fifth Screening in the European Randomized Study of Screening for Prostate Cancer Rotterdam: Can We Selectively Detect High-grade Prostate Cancer with Upfront Multivariable Risk Stratification and Magnetic Resonance Imaging?

BACKGROUND: The harm of screening (unnecessary biopsies and overdiagnosis) generally outweighs the benefit of reducing prostate cancer (PCa) mortality in men aged ≥70 yr. Patient selection for biopsy using risk stratification and magnetic resonance imaging (MRI) may improve this benefit-to-harm ratio. OBJECTIVE: To assess the potential of a risk-based strategy including MRI to selectively identify men aged ≥70 yr with high-grade PCa. DESIGN, SETTING, AND PARTICIPANTS: Three hundred and thirty-seven men with prostate-specific antigen ≥3.0 ng/ml at a fifth screening (71-75 yr) in the European Randomized study of Screening for Prostate Cancer Rotterdam were biopsied. One hundred and seventy-nine men received six-core transrectal ultrasound biopsy (TRUS-Bx), while 158 men received MRI, 12-core TRUS-Bx, and fusion TBx in case of Prostate Imaging Reporting and Data System ≥3 lesions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the overall, low-grade (Gleason Score 3+3) and high-grade (Gleason Score ≥ 3+4) PCa rate. Secondary outcome was the low- and high-grade PCa rate detected by six-core TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx. Tertiary outcome was the reduction of biopsies and low-grade PCa detection by upfront risk stratification with the Rotterdam Prostate Cancer Risk Calculator 4. RESULTS AND LIMITATIONS: Fifty-five percent of men were previously biopsied. The overall, low-grade, and high-grade PCa rates in biopsy naïve men were 48%, 27%, and 22%, respectively. In previously biopsied men these PCa rates were 25%, 20%, and 5%. Sextant TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx had a similar high-grade PCa rate (11%, 12%, and 11%) but a significantly different low-grade PCa rate (17%, 28%, and 7%). Rotterdam Prostate Cancer Risk Calculator 4-based stratification combined with 12-core TRUS-Bx ± MRI-TBx would have avoided 65% of biopsies and 68% of low-grade PCa while detecting an equal percentage of high-grade PCa (83%) compared with a TRUS-Bx all men approach (79%). CONCLUSIONS: After four repeated screens and ≥1 previous biopsies in half of men, a significant proportion of men aged ≥70 yr still harbor high-grade PCa. Upfront risk stratification and the combination of MRI and TRUS-Bx would have avoided two-thirds of biopsies and low-grade PCa diagnoses in our cohort, while maintaining the high-grade PCa detection of a TRUS-Bx all men approach. Further studies are needed to verify these results. PATIENT SUMMARY: Prostate cancer screening reduces mortality but is accompanied by unnecessary biopsies and overdiagnosis of nonaggressive tumors, especially in repeatedly screened elderly men. To tackle these drawbacks screening should consist of an upfront risk-assessment followed by magnetic resonance imaging and transrectal ultrasound-guided biopsy.

Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention, but Patients Should be Referred to a Tertiary Referral Centre.

BACKGROUND: When a liver lesion diagnosed as focal nodular hyperplasia (FNH) increases in size, it may cause doubt about the initial diagnosis. In many cases, additional investigations will follow to exclude hepatocellular adenoma or malignancy. This retrospective cohort study addresses the implications of growth of FNH for clinical management. METHODS: We included patients diagnosed with FNH based on ≥2 imaging modalities between 2002 and 2015. Characteristics of patients with growing FNH with sequential imaging in a 6-month interval were compared to non-growing FNH. RESULTS: Growth was reported in 19/162 (12%) patients, ranging from 21 to 200%. Resection was performed in 4/19 growing FNHs; histological examination confirmed FNH in all patients. In all 15 conservatively treated patients, additional imaging confirmed FNH diagnosis. No adverse outcomes were reported. No differences were found in characteristics and presentation of patients with growing or non-growing FNH. CONCLUSION: This study confirms that FNH may grow significantly without causing symptoms. A significant increase in size should not have any implications on clinical management if confident diagnosis by imaging has been established by a tertiary benign liver multidisciplinary team. Liver biopsy is only indicated in case of doubt after state-of-the-art imaging. Resection is deemed unnecessary if the diagnosis is confirmed by multiple imaging modalities in a tertiary referral centre.

The TRENDY multi-center randomized trial on hepatocellular carcinoma - Trial QA including automated treatment planning and benchmark-case results.

BACKGROUND AND PURPOSE: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported. MATERIALS AND METHODS: Scans of a single patient were used as a benchmark case. Contours submitted by nine participating centers were compared with reference contours. The subsequent planning round was based on a single set of contours. A total of 20 plans from participating centers, including 12 from the benchmark case, 5 from a clinical pilot and 3 from the first study patients, were compared to automatically generated VMAT plans. RESULTS: For the submitted liver contours, Dice Similarity Coefficients (DSC) with the reference delineation ranged from 0.925 to 0.954. For the GTV, the DSC varied between 0.721 and 0.876. For the 12 plans on the benchmark case, healthy liver normal-tissue complication probabilities (NTCPs) ranged from 0.2% to 22.2% with little correlation between NCTP and PTV-D95% (R2 < 0.3). Four protocol deviations were detected in the set of 20 treatment plans. Comparison with co-planar autoVMAT QA plans revealed these were due to too high target dose and suboptimal planning. Overall, autoVMAT resulted in an average liver NTCP reduction of 2.2 percent point (range: 16.2 percent point to -1.8 percent point, p = 0.03), and lower doses to the healthy liver (p < 0.01) and gastrointestinal organs at risk (p < 0.001). CONCLUSIONS: Delineation variation resulted in feedback to participating centers. Automated treatment planning can play an important role in clinical trials for prospective plan QA as suboptimal plans were detected.