Surveillance for Pancreatic Cancer in High-Risk Individuals Leads to Improved Outcomes: A Propensity Score-Matched Analysis.

BACKGROUND & AIMS: Recent pancreatic cancer surveillance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) in patients with a CDKN2A/p16 pathogenic variant diagnosed under surveillance are better as compared with patients with PDAC diagnosed outside surveillance. METHODS: In a propensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage, and survival between patients diagnosed under surveillance with non-surveillance patients with PDAC. Survival analyses were adjusted for potential effects of lead time. RESULTS: Between January 2000 and December 2020, 43,762 patients with PDAC were identified from the Netherlands Cancer Registry. Thirty-one patients with PDAC under surveillance were matched in a 1:5 ratio with 155 non-surveillance patients based on age at diagnosis, sex, year of diagnosis, and tumor location. Outside surveillance, 5.8% of the patients had stage I cancer, as compared with 38.7% of surveillance patients with PDAC (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). In total, 18.7% of non-surveillance patients vs 71.0% of surveillance patients underwent a surgical resection (OR, 10.62; 95% CI, 4.56-26.63). Patients in surveillance had a better prognosis, reflected by a 5-year survival of 32.4% and a median overall survival of 26.8 months vs 4.3% 5-year survival and 5.2 months median overall survival in non-surveillance patients (hazard ratio, 0.31; 95% CI 0.19-0.50). For all adjusted lead times, survival remained significantly longer in surveillance patients than in non-surveillance patients. CONCLUSION: Surveillance for PDAC in carriers of a CDKN2A/p16 pathogenic variant results in earlier detection, increased resectability, and improved survival as compared with non-surveillance patients with PDAC.

Neoadjuvant Treatment with Angiogenesis-Inhibitor Dovitinib Prior to Local Therapy in Hepatocellular Carcinoma: A Phase II Study.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early- and intermediate-stage HCC. MATERIALS AND METHODS: Twenty-four patients with modified Child-Pugh class A early- and intermediate-stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR-blockade, time to progression (TTP), and overall survival (OS). RESULTS: Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3-4 adverse events, most frequently (on-target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF-A, VEGF-D, and placental growth factor increased significantly, whereas sTie-2 decreased, consistent with VEGFR-blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer-specific survival was not reached. CONCLUSION: Already after a short 4-week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. IMPLICATIONS FOR PRACTICE: Orthotopic liver transplantation may cure early and intermediate-stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing.

Venous wedge and segment resection during pancreatoduodenectomy for pancreatic cancer: impact on short- and long-term outcomes in a nationwide cohort analysis.

BACKGROUND: Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival. METHODS: This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013-2017). RESULTS: A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P < 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P < 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P < 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33 months, respectively; P = 0.470), although there was a difference in major morbidity rates (52 versus 19 versus 21 per cent, respectively; P = 0.012). CONCLUSION: In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection.

Feasibility of Velocity-Selective Arterial Spin Labeling in Breast Cancer Patients for Noncontrast-Enhanced Perfusion Imaging.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based contrast agent, screening with DCE-MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast-enhanced alternative to DCE is desirable. PURPOSE: To investigate whether velocity selective arterial spin labeling (VS-ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue. STUDY TYPE: Prospective. POPULATION: Eight breast cancer patients. FIELD STRENGTH/SEQUENCE: A 3 T; VS-ASL with multislice single-shot gradient-echo echo-planar-imaging readout. ASSESSMENT: VS-ASL scans were independently assessed by three radiologists, with 3-25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3-point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI-RADS lexicon), as assessed in the standard clinical exam. STATISTICAL TESTS: Intra-class correlation coefficient (ICC) for interobserver agreement. RESULTS: The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score. DATA CONCLUSION: We have demonstrated the technical feasibility of bilateral whole-breast perfusion imaging using VS-ASL in breast cancer patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Surgical management and pathological assessment of pancreatoduodenectomy with venous resection: an international survey among surgeons and pathologists.

BACKGROUND: The aim of this survey was to gain insights in the current surgical management and pathological assessment of pancreatoduodenectomy with portal-superior mesenteric vein resection (VR). METHODS: A systematic literature search was performed to identify international expert surgeons (N = 150) and pathologists (N = 40) who published relevant studies between 2009 and 2019. These experts and Dutch surgeons (N = 17) and pathologists (N = 20) were approached to complete an online survey. RESULTS: Overall, 76 (46%) surgeons and 37 (62%) pathologists completed the survey. Most surgeons (71%) estimated that preoperative imaging corresponded correctly with intraoperative findings of venous involvement in 50-75% of patients. An increased complication risk following VR was expected by 55% of surgeons, mainly after Type 4 (segmental resection-venous conduit anastomosis). Most surgeons (61%) preferred Type 3 (segmental resection-primary anastomosis). Most surgeons (75%) always perform the VR themselves. Standard postoperative imaging for patency control was performed by 54% of surgeons and 39% adjusted thromboprophylaxis following VR. Most pathologists (76%) always assessed tumor infiltration in the resected vein and only 54% of pathologists always assess the resection margins of the vein itself. Variation in assessment of tumor infiltration depth was observed. CONCLUSION: This international survey showed variation in the surgical management and pathological assessment of pancreatoduodenectomy with venous involvement. This highlights the lack of evidence and emphasizes the need for research on imaging modalities to improve patient selection for VR, surgical techniques, postoperative management and standardization of the pathological assessment.

Dilatation of the main pancreatic duct as first manifestation of small pancreatic ductal adenocarcinomas detected in a hereditary pancreatic cancer surveillance program.

BACKGROUND: MRI surveillance in a cohort of CDKN2A-p16-Leiden mutation carriers with a 20% lifetime risk of PDAC led to increased resection rates and improved survival. Patients with screen-detected PDAC were evaluated for main pancreatic duct (MPD) abnormalities in this retrospective review. METHODS: Since 2000 annual MRI and optional EUS was performed in mutation carriers. Data of patients with screen-detected PDAC was collected on gender, age at diagnosis, site of tumor, size, outcome of surgery, pathology findings and survival. All MRIs were re-evaluated for MPD abnormalities. RESULTS: 23 PDAC were detected in 22 (10%) of 217 mutation carriers, 10 (45%) males and 12 (55%) females. The mean age at diagnosis was 59.8 years (range 39.2-74.3 years). Revision of the MRI/MRCP revealed a lesion and dilatation of the MPD in 8 of the 22 patients. In 5 of 7 patients with PDAC detected during follow-up, the previous MRI showed MPD dilatation without evidence of tumor. The mean size of PDAC was 12.3 mm (range 5-19 mm). All tumors were resectable. CONCLUSION: MPD dilation is common in patients with screen-detected PDAC. Abnormalities on MRI during surveillance of high-risk individuals requires intense follow-up or prompt treatment, as early treatment results in a better prognosis.

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: Patients with perianal fistulizing Crohn's disease have a poor prognosis because these lesions do not heal well. We evaluated the effects of local administration of bone marrow-derived mesenchymal stromal cells (MSCs) to these patients from healthy donors in a double-blind, placebo-controlled study. METHODS: Twenty-one patients with refractory perianal fistulizing Crohn's disease were randomly assigned to groups given injections of 1 × 10(7) (n = 5, group 1), 3 × 10(7) (n = 5, group 2), or 9 × 10(7) (n = 5, group 3) MSCs, or placebo (solution with no cells, n = 6), into the wall of curettaged fistula, around the trimmed and closed internal opening. The primary outcome, fistula healing, was determined by physical examination 6, 12, and 24 weeks later; healing was defined as absence of discharge and <2 cm of fluid collection-the latter determined by magnetic resonance imaging at week 12. All procedures were performed at Leiden University Medical Center, The Netherlands, from June 2012 through July 2014. RESULTS: No adverse events were associated with local injection of any dose of MSCs. Healing at week 6 was observed in 3 patients in group 1 (60.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 1 patient in the placebo group (16.7%) (P = .08 for group 2 vs placebo). At week 12, healing was observed in 2 patients in group 1 (40.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 2 patients in the placebo group (33.3%); these effects were maintained until week 24 and even increased to 4 (80.0%) in group 1. At week six, 4 of 9 individual fistulas had healed in group 1 (44.4%), 6 of 7 had healed in group 2 (85.7%), and 2 of 7 had healed in group 3 (28.6%) vs 2 of 9 (22.2%) in the placebo group (P = .04 for group 2 vs placebo). At week twelve, 3 of 9 individual fistulas had healed in group 1 (33.3%), 6 of 7 had healed in group 2 (85.7%), 2 of 7 had healed in group 3 (28.6%), and 3 of 9 had healed in the placebo group (33.3%). These effects were stable through week 24 and even increased to 6 of 9 (66.7%) in group 1 (P = .06 group 2 vs placebo, weeks 12 and 24). CONCLUSIONS: Local administration of allogeneic MSCs was not associated with severe adverse events in patients with perianal fistulizing Crohn's disease. Injection of 3 × 10(7) MSCs appeared to promote healing of perianal fistulas. ClinicalTrials.gov ID NCT01144962.

Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial.

BACKGROUND: Doxycycline inhibits formation and progression of abdominal aortic aneurysms (AAAs) in preclinical models of the disease, but it is unclear whether and how this observation translates to humans. OBJECTIVE: To test whether doxycycline inhibits AAA progression in humans. DESIGN: Randomized, placebo-controlled, double-blind trial. (Dutch Trial Registry: NTR 1345) SETTING: 14 Dutch hospitals. PATIENTS: 286 patients with small AAAs between October 2008 and June 2011. INTERVENTION: Daily dose of 100 mg of doxycycline (n = 144) or placebo (n = 142) for 18 months. MEASUREMENTS: The primary outcome measure was aneurysm growth at 18 months, as estimated by repeated single-observer ultrasonography. Secondary outcomes included growth at 6 and 12 months and the need for elective surgery. RESULTS: Mean aneurysm diameter (approximately 43 mm) and other baseline characteristics were similar in both groups. Doxycycline treatment was associated with increased aneurysm growth (4.1 mm in the doxycycline group vs. 3.3 mm in the placebo group at 18 months; difference, 0.8 mm [95% CI, 0.1 to 1.4 mm]; P = 0.016 mm). Twenty-one patients receiving doxycycline and 22 patients receiving placebo had elective surgical repair (Kaplan­Meier estimates were 16.1% for those receiving doxycycline and 16.5% for those receiving placebo; difference, -0.4% [CI, -9.3% to 8.5%]; P = 0.83). Time to repair was similar in the groups (P = 0.92). LIMITATIONS: This study focuses on patients with small AAAs. As such, whether the data can be extrapolated to larger AAAs (>55 mm) is unclear. The high number of elective repairs (n = 43) was unanticipated. Moreover, the study did not follow patients who withdrew because of an adverse effect. CONCLUSION: This trial found that 18 months of doxycycline therapy did not reduce aneurysm growth and did not influence the need for AAA repair or time to repair. PRIMARY FUNDING SOURCE: The Netherlands Organisation for Health Research and Development, and the NutsOhra Fund.

Aspects and outcomes of surveillance for individuals at high-risk of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.

Screening for pancreatic cancer in high-risk individuals using MRI: optimization of scan techniques to detect small lesions.

Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.

The Added Value of Blood Glucose Monitoring in High-Risk Individuals Undergoing Pancreatic Cancer Surveillance.

OBJECTIVES: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. MATERIALS AND METHODS: High-risk individuals with a CDKN2A/p16 germline pathogenic variant participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve was computed. RESULTS: In total, 220 HRIs were included between 2000 and 2019. Median age was 61 (interquartile range. 53-71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (odds ratio, 1.21; 95% confidence interval, 0.39-3.78) and 4 of 5 PDAC cases seemed to have NOD within 3 months before diagnosis. Furthermore, NOD did not differentiate between HRIs with and without PDAC (area under the curve, 0.54; 95% confidence interval, 0.46-0.61). CONCLUSIONS: In this study, we found no added value for longitudinal glucose monitoring in CDKN2A pathogenic variant carriers participating in an imaging-based pancreatic cancer surveillance program.

Reliability and differentiation of pelvic floor muscle electromyography measurements in healthy volunteers using a new device: the Multiple Array Probe Leiden (MAPLe).

AIMS: A new multiple electrode probe, the Multiple Array Probe Leiden (MAPLe), has been developed for biofeedback registration of the individual pelvic floor musculature (PFM). The aim was to determine the reliability and differentiation of electromyography (EMG) signals measured with the MAPLe in healthy volunteers. METHODS: Two hundred twenty nine healthy volunteers not seeking treatment or using medication for symptoms of prolapse, lower urinary tract, bowel, pain, and/or sexual function related to pelvic floor dysfunction were qualified to participate. Subjects were asked to perform five tasks: rest, maximum voluntary contractions, endurance, cough, and valsalva. Mean EMG values per electrode were registered. Test-retest reliability was assessed using linear mixed model with random subject effects. One-way ANOVA tests were performed to detect differences between groups. RESULTS: Magnetic resonance imaging (MRI) showed that each of the electrodes could be related nearest to the individual muscles. For test-retest, the intraclass correlation ranged from 0.53 to 0.91. The MAPLe showed significant differences in average EMG values between men and women, and between nulliparous and parous, pre- and prostmenpausal women. Significant differences were seen between the left and right sides of the pelvic floor. In addition, the activity nearest to the individual pelvic floor muscles (external anal sphincter (EAS), puborectalis muscle, bulbospongiosus, ischiocavernosus and the pubococcygeus muscle) could be determined. CONCLUSIONS: The MAPLe is a reliable instrument measuring the EMG signals of the different sides and levels nearest to the pelvic floor musculature and is capable to differentiate between men and women, nulliparous, parous, pre- and postmenopausal. The findings of this study have implications for the diagnosis and treatment of pelvic floor dysfunction in the future.

Feasibility of In Vivo Metal Artifact Reduction in Contrast-Enhanced Dedicated Spiral Breast Computed Tomography.

BACKGROUND: Radiopaque breast markers cause artifacts in dedicated spiral breast-computed tomography (SBCT). This study investigates the extent of artifacts in different marker types and the feasibility of reducing artifacts through a metal artifact reduction (MAR) algorithm. METHODS: The pilot study included 18 women who underwent contrast-enhanced SBCT. In total, 20 markers of 4 different types were analyzed for artifacts. The extent of artifacts with and without MAR was measured via the consensus of two readers. Image noise was quantitatively evaluated, and the effect of MAR on the detectability of breast lesions was evaluated on a 3-point Likert scale. RESULTS: Breast markers caused significant artifacts that impaired image quality and the detectability of lesions. MAR decreased artifact size in all analyzed cases, even in cases with multiple markers in a single slice. The median length of in-plain artifacts significantly decreased from 31 mm (range 11-51 mm) in uncorrected to 2 mm (range 1-5 mm) in corrected images (p ≤ 0.05). Artifact size was dependent on marker size. Image noise in slices affected by artifacts was significantly lower in corrected (13.6 ± 2.2 HU) than in uncorrected images (19.2 ± 6.8 HU, p ≤ 0.05). MAR improved the detectability of lesions affected by artifacts in 5 out of 11 cases. CONCLUSION: MAR is feasible in SBCT and improves the image quality and detectability of lesions.

Cost-effectiveness of pancreas surveillance: The CDKN2A-p16-Leiden cohort.

BACKGROUND: CDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis. OBJECTIVE: To assess the cost-effectiveness of surveillance, as compared to no surveillance. METHODS: In 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen-detected tumors and on survival. The Kaplan-Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state-transition model was constructed to estimate lifelong outcomes. RESULTS: A total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long-term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by €13,900 per patient, with a cost-utility ratio of €14,000 per quality-adjusted life year gained. For annual surveillance to have an acceptable cost-effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher. CONCLUSION: The tumor could be resected in most patients with a screen-detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost-effective.

Practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer: A nationwide cohort study.

BACKGROUND: Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study explores the potential causes and consequences of practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer in the Netherlands. METHODS: This nationwide retrospective cohort study included patients undergoing pancreatoduodenectomy for pancreatic cancer in 18 centers from 2013 through 2017. RESULTS: Among 1,311 patients undergoing pancreatoduodenectomy, 351 (27%) had a venous resection, and the overall median annual center volume of venous resection was 4. No association was found between the center volume of pancreatoduodenectomy and the rate of venous resections, nor between patient and tumor characteristics and the rate of venous resections per center. Female sex, lower body mass index, neoadjuvant therapy, venous involvement, and stenosis on imaging were predictive for venous resection. Adjusted for these factors, 3 centers performed significantly more, and 3 centers performed significantly fewer venous resections than expected. In patients with venous resection, significantly less major morbidity (22% vs 38%) and longer overall survival (median 16 vs 12 months) were observed in centers with an above-median annual volume of venous resections (>4). CONCLUSION: Patient and tumor characteristics did not explain significant practice variation between centers in the Netherlands in venous resection during pancreatoduodenectomy for pancreatic cancer. The clinical outcomes of venous resection might be related to the volume of the procedure.

Pancreatic Cancer Surveillance in Carriers of a Germline CDKN2A Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up.

PURPOSE: Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A. METHODS: Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound. RESULTS: Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia. CONCLUSION: This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.

Assessment of false-negative cases of breast MR imaging in women with a familial or genetic predisposition.

In order to assess the characteristics of malignant breast lesions those were not detected during screening by MR imaging. In the Dutch MRI screening study(MRISC), a non-randomized prospective multicenter study,women with high familial risk or a genetic predisposition for breast cancer were screened once a year by mammography and MRI and every 6 months with a clinical breast examination (CBE). The false-negative MR examinations were subject of this study and were retrospectively reviewed by two experienced radiologists. From November 1999 until March 2006, 2,157 women were eligible for study analyses. Ninety-seven malignant breast tumors were detected, including 19 DCIS (20%). In 22 patients with a malignant lesion, the MRI was assessed as BI-RADS 1 or 2. One patient was excluded because the examinations were not available for review. Forty-three percent (9/21) of the false-negative MR cases concerned pure ductal carcinoma in situ (DCIS) or DCIS with invasive foci, in eight of them no enhancement was seen at the review. In six patients the features of malignancy were missed or misinterpreted.Small lesion size (n = 3), extensive diffuse contrast enhancement of the breast parenchyma (n = 2),and a technically inadequate examination (n = 1) were other causes of the missed diagnosis. A major part of the false-negative MR diagnoses concerned non-enhancing DCIS, underlining the necessity of screening not only with MRI but also with mammography. Improvement of MRI scanning protocols may increase the detection rate of DCIS. The missed and misinterpreted cases are reflecting the learning curve of a multicenter study.

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for MR angiography of peripheral arteries.

PURPOSE: To prospectively compare the image quality and diagnostic performance achieved with doses of gadobenate dimeglumine and gadopentetate dimeglumine of 0.1 mmol per kilogram of body weight in patients undergoing contrast material-enhanced magnetic resonance (MR) angiography of the pelvis, thigh, and lower-leg (excluding foot) for suspected or known peripheral arterial occlusive disease. MATERIALS AND METHODS: Institutional review board approval was granted from each center and informed written consent was obtained from all patients. Between November 2006 and January 2008, 96 patients (62 men, 34 women; mean age, 63.7 years +/- 10.4 [standard deviation]; range, 39-86 years) underwent two identical examinations at 1.5 T by using three-dimensional spoiled gradient-echo sequences and randomized 0.1-mmol/kg doses of each agent. Images were evaluated on-site for technical adequacy and quality of vessel visualization and offsite by three independent blinded readers for anatomic delineation and detection/exclusion of pathologic features. Comparative diagnostic performance was determined in 31 patients who underwent digital subtraction angiography. Data were analyzed by using the Wilcoxon signed-rank, McNemar, and Wald tests. Interreader agreement was determined by using generalized kappa statistics. Differences in quantitative contrast enhancement were assessed and a safety evaluation was performed. RESULTS: Ninety-two patients received both agents. Significantly better performance (P < .0001; all evaluations) with gadobenate dimeglumine was noted on-site for technical adequacy and vessel visualization quality and offsite for anatomic delineation and detection/exclusion of pathologic features. Contrast enhancement (P < or = .0001) and detection of clinically relevant disease (P < or = .0028) were significantly improved with gadobenate dimeglumine. Interreader agreement for stenosis detection and grading was good to excellent (kappa = 0.749 and 0.805, respectively). Mild adverse events were reported for four (six events) and five (eight events) patients after gadobenate dimeglumine and gadopentetate dimeglumine, respectively. CONCLUSION: Higher-quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease.

Magnetic Resonance Thrombus Imaging to Differentiate Acute from Chronic Portal Vein Thrombosis.

Introduction Timely diagnosis and treatment of portal vein thrombosis (PVT) is crucial to prevent morbidity and mortality. However, current imaging tests cannot always accurately differentiate acute from chronic (nonocclusive) PVT. Magnetic resonance noncontrast thrombus imaging (MR-NCTI) has been shown to accurately differentiate acute from chronic venous thrombosis at other locations and may also be of value in the diagnostic management of PVT. This study describes the first phase of the Rhea study (NTR 7061). Our aim was to select and optimize MR-NCTI sequences that would be accurate for differentiation of acute from chronic PVT. Study Design The literature was searched for different MRI sequences for portal vein and acute thrombosis imaging. The most promising sequences were tested in a healthy volunteer followed by one patient with acute PVT and two patients with chronic PVT, all diagnosed on (repetitive) contrast-enhanced computed tomography (CT) venography to optimize the MR-NCTI sequences. All images were evaluated by an expert panel. Results Several MR-NCTI sequences were identified and tested. Differentiation of acute from chronic PVT was achieved with 3D T1 TFE (three-dimensional T1 turbo field echo) and 3D T1 Dixon FFE (three-dimensional T1 fast field echo) sequences with best image quality. The expert panel was able to confirm the diagnosis of acute PVT on the combined two MR-NCTI sequences and to exclude acute PVT in the two patients with chronic PVT. Conclusion Using 3D T1 TFE and 3D T1 Dixon FFE sequences, we were able to distinguish acute from chronic PVT. This clinical relevant finding will be elucidated in clinical studies to establish their test performance.

Correlation of the tumour-stroma ratio with diffusion weighted MRI in rectal cancer.

OBJECTIVE: This study evaluated the correlation between intratumoural stroma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer. METHODS: This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients. Two observers measured the mean and minimum ADCs based on single-slice and whole-volume segmentations. The TSR was determined on diagnostic haematoxylin & eosin stained slides of rectal tumour biopsies. The correlation between TSR and ADC was assessed by Spearman correlation (rs). RESULTS: The ADC values between stroma-low and stroma-high tumours were not significantly different. Intra-class correlation (ICC) demonstrated a good level of agreement for the ADC measurements, ranging from 0.84-0.86 for single slice and 0.86-0.90 for the whole-volume protocol. No correlation was observed between the TSR and ADC values, with ADCmeanrs= -0.162 (p= 0.38) and ADCminrs= 0.041 (p= 0.82) for the single-slice and rs= -0.108 (p= 0.55) and rs= 0.019 (p= 0.92) for the whole-volume measurements in the training cohort, respectively. Results from the validation cohort were consistent; ADCmeanrs= -0.022 (p= 0.86) and ADCminrs = 0.049 (p= 0.69) for the single-slice and rs= -0.064 (p= 0.59) and rs= -0.063 (p= 0.61) for the whole-volume measurements. CONCLUSIONS: Reproducibility of ADC values is good. Despite positive reports on the correlation between TSR and ADC values in other tumours, this could not be confirmed for rectal cancer.