Maria Antonietta Bali

MR urography in children.

Thanks to the development of rapid sequences with better resolution, applications of uro MR have rapidly increased in children. Difficulties that remain are related to the variable ages of the patients. It is therefore mandatory to standardize as much as possible the techniques that are used in order to obtain reproducible results. In this review, the examination protocols will be explained. In a second part the current applications in children will be illustrated and discussed, especially in comparison with the other imaging techniques.

Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

Cancer organoids to model therapy response Cancer organoids are miniature, three-dimensional cell culture models that can be made from primary patient tumors and studied in the laboratory. Vlachogiannis et al. asked whether such “tumor-in-a-dish” approaches can be used to predict drug responses in the clinic. They generated a live organoid biobank from patients with metastatic gastrointestinal cancer who had previously been enrolled in phase I or II clinical trials. This allowed the authors to compare organoid drug responses with how the patient actually responded in the clinic. Encouragingly, the organoids had similar molecular profiles to those of the patient tumor, reinforcing their value as a platform for drug screening and development. Science, this issue p. 920 Organoids can recapitulate patient responses in the clinic, with potential for drug screening and personalized medicine. Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.

New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel

Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

ENDOSCOPIC THERAPY FOR CHRONIC PANCREATITIS

When endoscopic therapy is used for the treatment of patients with painful chronic pancreatitis, extracorporeal shock wave lithotripsy (ESWL) can be proposed as a first-line approach when obstructive ductal stone(s) induce upstream dilation of the main pancreatic duct. Stone fragmentation by ESWL is followed by endoscopic ductal drainage using pancreatic sphincterotomy, fragmented stone(s) extraction, and pancreatic stenting in case of ductal stricture. After completion of endoscopic pancreatic ductal drainage, long-term clinical benefit can be expected for two thirds of the patients. Best clinical results are associated with absence or cessation of smoking and with early treatment in the course of chronic pancreatitis, while alcohol abuse increases the risks of diabetes, steatorrhea and mortality. The complications of chronic pancreatitis are mainly the development of pseudocyst secondary to the downstream ductal obstruction, and biliary obstruction caused by fibrotic changes in the head of the pancreas. Successful endoscopic pseudocyst drainage is currently obtained in most patients, and carries a low complication rate. Biliary stenting is a safe and effective technique for the short-term treatment of symptomatic bile duct stricture due to chronic pancreatitis, but permanent resolution is obtained in only 25% of cases. In conclusion, endoscopic management is now considered to be the preferred interventional treatment of chronic pancreatitis, for patients selected on the basis of the anatomical changes caused by the disease. This treatment is generally safe, minimally invasive, often effective for years, does not prevent further surgery, and can be repeated.

Tumoral and Nontumoral Pancreas: Correlation between Quantitative Dynamic Contrast-enhanced MR Imaging and Histopathologic Parameters

PURPOSE To prospectively determine whether dynamic contrast material-enhanced (DCE) magnetic resonance (MR) quantitative parameters correlate with fibrosis and microvascular density (MVD) in malignant and benign solid pancreatic focal lesions and nontumoral pancreatic tissue. MATERIALS AND METHODS The institutional review board approved the study; written informed consent was obtained. DCE MR was performed in 28 patients with surgically resectable focal pancreatic lesions. DCE MR quantitative parameters derived from one-compartment (OC) (transfer rate constant [K(trans)] and distribution fraction [ƒ]) and two-compartment (TC) (K(trans), tissue volume fraction occupied by extravascular extracellular space [v(i)], and tissue volume fraction occupied by vascular space [v(p)]) pharmacokinetic models were correlated with fibrosis content and MVD counts in focal lesions and nontumoral tissue (Spearman correlation coefficient [SCC]). Pharmacokinetic parameters were compared (Mann-Whitney test) between tumoral and nontumoral tissue. Diagnostic performance of DCE MR fibrosis detection was assessed (receiver operator characteristic curve analysis). RESULTS K(trans) OC and K(trans) TC were significantly lower in primary malignant tumors compared with benign lesions (P = .023) and nontumoral pancreatic tissue downstream (P < .001) and upstream (P = .006); ƒ and v(i) were significantly higher in primary malignant tumors compared with nontumoral pancreatic tissue downstream (P = .012 and .018, respectively). Fibrosis was correlated negatively with K(trans) OC (SCC, -0.600) and K(trans) TC (SCC, -0.564) and positively with ƒ (SCC, 0.514) and v(i) (SCC, 0.464), with P < .001 (all comparisons). MVD was positively correlated with ƒ (SCC, 0.355; P = .019) and v(i) (SCC, 0.297; P = .038) but not with K(trans) OC (SCC, -0.140; P = .33) and K(trans) TC (SCC, -0.194; P = .181). Sensitivity and specificity for fibrosis detection were 65% (24 of 37) and 83% (10 of 12) for K(trans) OC (cutoff value, 0.35 min(-1)) and 76% (28 of 37) and 83% (10 of 12) for K(trans) TC (cutoff value, 0.29 min(-1)), respectively. CONCLUSION Quantitative DCE MR parameters, derived from pharmacokinetic models in malignant and benign pancreatic solid lesions and nontumoral pancreatic tissue, were significantly correlated with fibrosis and MVD. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11103515/-/DC1.

Pancreatic perfusion: noninvasive quantitative assessment with dynamic contrast-enhanced MR imaging without and with secretin stimulation in healthy volunteers--initial results.

PURPOSE To prospectively quantify pancreatic regional perfusion with dynamic contrast material-enhanced magnetic resonance (MR) imaging by using a one-compartment model and to assess perfusion changes during secretin stimulation in healthy volunteers. MATERIALS AND METHODS The study had institutional review board approval, and written informed consent was obtained. Ten healthy volunteers (five men, five women; mean age, 24.7 years +/- 1.9 [standard deviation]; range, 22-29 years) underwent MR imaging pancreatic perfusion studies performed twice without secretin and twice during secretin stimulation. Dynamic contrast-enhanced MR imaging consisted of saturation-recovery T1-weighted turbo-field-echo imaging with peripheral pulse triggering and respiratory tracking. A dose of 0.05 mmol gadodiamide per kilogram of body weight was injected at a rate of 3.5 mL/sec. Regional perfusion parameters were fitted with a one-compartment model. The analysis of variance test for repeated measurements was used to assess differences in pancreatic perfusion without and that with secretin administration. RESULTS Significant differences in perfusion parameters between the three pancreatic regions were observed (P < .05). During secretin stimulation, a significant difference was observed only between the body and the tail of the pancreas (P = .02). A significant increase (P = .003) in pancreatic perfusion was observed after secretin administration. Mean pancreatic perfusion was 184 mL/min/100 g of tissue +/- 71, 207 mL/min/100 g +/- 77, and 230 mL/min/100 g +/- 87 without secretin and 342 mL/min/100 g +/- 154, 338 mL/min/100 g +/- 156, and 373 mL/min/100 g +/- 176 after secretin stimulation in the head, body, and tail of the pancreas, respectively. Intraindividual variability was 21% without secretin stimulation and 46% with secretin stimulation. CONCLUSION Dynamic contrast-enhanced MR imaging enables noninvasive quantification of regional pancreatic perfusion in resting conditions and demonstrates the increase in pancreatic perfusion during secretin stimulation in healthy subjects.

Pancreatic neuroendocrine tumor: Added value of fusion of T2-weighted imaging and high b-value diffusion-weighted imaging for tumor detection

OBJECTIVES To investigate the added value of fusion of high b-value diffusion-weighted images (DWI) and T2-weighted (T2) MR images for the detection of pancreatic neuroendocrine tumors (PNT). METHODS 18 patients with 18 histologically proven PNT were included. Two radiologists independently and retrospectively reviewed four randomized images sets (T2+T1, DWI, T2+DWI, and DWI+T2 fusion). Lesion detection confidence level was assessed using a three grade score (no lesion; uncertain lesion and certain lesion); lesion size and signal intensity were recorded. Apparent diffusion coefficients (ADC) of tumor and adjacent pancreas were measured. RESULTS Readers 1 and 2 respectively detected 14/18 and 16/18 lesions on T2+T1, 13/18 and 12/18 on DWI, 16/18 and 15/18 on T2+DWI and 17/18 and 16/18 on DWI+T2 fusion. Lesion median size was 16 mm (range: 7 mm-40 mm), 22% were hyperfunctioning (all insulinomas) and 72% were low-grade (Rindi 1). All tumors except one (with cystic component) showed lower ADC than adjacent pancreatic parenchyma. Fusion imaging had significantly better detection score by both authors (p<0.005) and provided the higher inter-reader agreement (kappa 0.7). DWI alone had the worst score for both readers. CONCLUSIONS Fusion images improve the detection of PNT, especially in patients with small isointense lesions on conventional MR sequences.

New challenges in perioperative management of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the industrialized world. Despite progress in the understanding of the molecular and genetic basis of this disease, the 5-year survival rate has remained low and usually does not exceed 5%. Only 20%-25% of patients present with potentially resectable disease and surgery represents the only chance for a cure. After decades of gemcitabine hegemony and limited therapeutic options, more active chemotherapies are emerging in advanced PDAC, like 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin and nab-paclitaxel plus gemcitabine, that have profoundly impacted therapeutic possibilities. PDAC is considered a systemic disease because of the high rate of relapse after curative surgery in patients with resectable disease at diagnosis. Neoadjuvant strategies in resectable, borderline resectable, or locally advanced pancreatic cancer may improve outcomes. Incorporation of tissue biomarker testing and imaging techniques into preoperative strategies should allow clinicians to identify patients who may ultimately achieve curative benefit from surgery. This review summarizes current knowledge of adjuvant and neoadjuvant treatment for PDAC and discusses the rationale for moving from adjuvant to preoperative and perioperative therapeutic strategies in the current era of more active chemotherapies and personalized medicine. We also discuss the integration of good specimen collection, tissue biomarkers, and imaging tools into newly designed preoperative and perioperative strategies.

Endotherapy for paraduodenal pancreatitis: A large retrospective case series

BACKGROUND AND STUDY AIMS Paraduodenal pancreatitis is histologically well defined but its epidemiology, natural history, and connection with chronic pancreatitis are not completely understood. The aim of this study was to review the endoscopic and medical management of paraduodenal pancreatitis. PATIENTS AND METHODS Medical records of all patients with paraduodenal pancreatitis diagnosed by magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasonography (EUS) between 1995 and 2010 were retrospectively reviewed. Clinical features, imaging procedures, and treatments were investigated. The primary end point was the rate of clinical success, and the secondary end points were the radiological or endoscopic improvement, complication rate, and overall survival rate. RESULTS A total of 51 patients were included in the study (88.2 % alcohol abuse; median age 49 years [range 37 - 70]; 50 men). The most frequent symptoms at presentation were pain (n = 50; 98.0 %) and weight loss (n = 36; 70.6 %). Chronic pancreatitis was present in 36 patients (70.6 %), and 45 patients (88.2 %) had cysts. Other findings included stricture of the pancreatic duct (n = 37; 72.5 %), common bile duct (n = 29; 56.9 %), and duodenum (n = 24; 47.1 %). A total of 39 patients underwent initial endoscopic treatment: cystenterostomy (n = 20), pancreatic and/or biliary duct drainage (n = 19), and/or duodenal dilation (n = 6). For the patients with available follow-up (n = 41), 24 patients required repeat endoscopy and 9 patients required surgery after the initial endoscopic management. After a median follow-up of 54 months (range 6 - 156 months), complete clinical success was achieved in 70.7 % of patients, and the overall survival rate was 94.1 %. CONCLUSIONS This is the largest series concerning the management of paraduodenal pancreatitis using endotherapy as the first-line intervention. Although repeat endoscopic procedures were required in half of the patients, no severe complication was observed and surgical treatment was ultimately needed in less than 25 % of the patients.

Focal liver lesions detection: Comparison of respiratory-triggering, triggering and tracking navigator and tracking-only navigator in diffusion-weighted imaging

PURPOSE To compare low b value (10s/mm(2)) spin-echo echo-planar (SE-EP) diffusion-weighted imaging (DWI) acquired with respiratory-triggering (RT), triggering and tracking navigator (TT), tracking only navigator (TRON) techniques for image quality and focal liver lesions (FLL) detection in non-cirrhotic patients. MATERIAL AND METHODS This bi-centric study was approved by the institutional review boards; informed consent was obtained. Eighty-three patients were prospectively included and SE-EP-DWI with RT, TT and TRON techniques were performed. DWI sequences were randomized and independently analyzed by two readers. The qualitative evaluation was based on a 3-point score for axial artifacts (motion, ghost, susceptibility artifacts and distortion) and stair-step artifacts. Sensitivity of FLL detection was calculated for all lesions together and after lesion size stratification (≤ 10 mm, >10-20mm and >20mm). The standard of reference consisted of a retrospective reading of the conventional MRI, the three DWI sequences and by follow-up (12 months): a total of 409 FLL were detected. Data between sequences was compared with non-parametric tests. Cohens kappa coefficient was used for inter-observer agreement. RESULTS Image quality was comparable for RT and TT. TRON showed statistically significantly more axial artifacts for the two readers (p<0.05). Stair-step artifacts were not statistically significantly different between DWI sequences. Overall sensitivities for RT, TT, TRON were 85%, 86%, 82% and 86%, 89% 83%, respectively, for readers 1 and 2. The inter-observer agreement was very good. CONCLUSION Image quality was better for RT and TT compared to TRON. Overall sensitivities for FLL detection were comparable between techniques and readers.