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We aimed to separate the influence of radiologist experience from that of CT quality in the evaluation of CT examinations of patients with esophageal or gastric cardia cancer. Two radiologists from referral centers ('expert radiologists') and six radiologists from regional non-referral centers ('non-expert radiologists') performed 240 evaluations of 72 CT examinations of patients diagnosed with esophageal or gastric cardia cancer between 1994 and 2003. We used conditional logistic regression analysis to calculate odds ratios (OR) for the likelihood of a correct diagnosis. Expert radiologists made a correct diagnosis of the presence or absence of distant metastases according to the gold standard almost three times more frequently (OR 2.9; 95% CI 1.4-6.3) than non-expert radiologists. For the subgroup of CT examinations showing distant metastases, a statistically significant correlation (OR 3.5; 95% CI 1.4-9.1) was found between CT quality as judged by the radiologists and a correct diagnosis. Both radiologist experience and quality of the CT examination play a role in the detection of distant metastases in esophageal or gastric cardia cancer patients. Therefore, we suggest that staging procedures for esophageal and gastric cardia cancer should preferably be performed in centers with technically advanced equipment and experienced radiologists. [ABSTRACT FROM AUTHOR]

Importance: In patients with colorectal cancer and unresectable liver-only metastases (CRLM), treatment with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) plus irinotecan (FOLFOXIRI) and bevacizumab vs FOLFOX/folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab increased progression-free survival, response, and R0/R1 resection/ablation rates, as well as toxic effects in RAS/BRAFV600E-variant and/or right-sided tumors. FOLFOX/FOLFIRI-panitumumab vs FOLFOX/FOLFIRI-bevacizumab increased response at the cost of more toxic effects in RAS/BRAFV600E wild-type, left-sided tumors., Objective: To present long-term outcomes of treatment with FOLFOXIRI plus bevacizumab vs FOLFOX/FOLFIRI plus bevacizumab and FOLFOX/FOLFIRI plus panitumumab vs FOLFOX/FOLFIRI + bevacizumab., Design, Setting, and Participants: The randomized phase 3 CAIRO5 trial included patients with initially unresectable CRLM in 46 Dutch centers and 1 Belgian center between November 2014 and January 2022. A liver expert panel repeatedly evaluated resectability., Intervention: Patients with RAS/BRAFV600E-variant and/or right-sided tumors randomly received FOLFOX/FOLFIRI-bevacizumab (group 1) or FOLFOXIRI-bevacizumab (group 2), and those with RAS/BRAFV600E wild-type, left-sided tumors received FOLFOX/FOLFIRI-bevacizumab (group 3) or FOLFOX/FOLFIRI-panitumumab (group 4). Adjuvant chemotherapy (ACT) after complete local treatment was recommended but not standard., Main Outcomes and Measures: Overall survival (OS) was analyzed as a secondary outcome. Other outcomes were post hoc analyses., Results: A total of 530 patients (327 male [62%] and 203 female individuals [38%]; median age, 62 [IQR, 54-69] years) were randomized: 148 in group 1, 146 in group 2, 118 in group 3, and 118 in group 4. The median OS in group 1 was 23.6 (95% CI, 20.1-27.5) vs 24.1 (95% CI, 21.0-30.9) months in group 2 (hazard ratio [HR], 0.90; 95% CI, 0.70-1.17; P = .44), and 39.9 (95% CI, 30.7-44.6) in group 3 vs 38.3 (95% CI, 35.3-51.3) months in group 4 (HR, 0.95; 95% CI, 0.68-1.32; P = .75). OS was longest after complete local treatment without early (≤6 months) recurrence (64.3 months; 95% CI, 57.6 to not reached) and salvage local treatment options after early recurrence (58.9; 95% CI, 47.3 to not reached), followed by patients without salvage local treatment after early recurrence (30.5; 95% CI, 24.4-33.4) and with incomplete local treatment (28.7; 95% CI, 25.9-38.3), and worst in patients with continued unresectability (18.3; 95% CI, 15.7-20.0). After confounder adjustment, ACT was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85)., Conclusions and Relevance: These results support using FOLFOX/FOLFIRI-bevacizumab for patients with initially unresectable CRLM irrespective of RAS/BRAFV600E status and tumor sidedness. Patients with complete local liver treatment with salvage local treatment in case of early recurrence had the longest OS. ACT might be considered for these patients., Trial Registration: ClinicalTrials.gov NCT02162563.

Ultrahigh field magnetic resonance imaging (MRI) (≥ 7 T) has the potential to provide superior spatial resolution and unique image contrast. Apart from radiofrequency transmit inhomogeneities in the body at this field strength, imaging of the upper abdomen faces additional challenges associated with motion-induced ghosting artifacts. To address these challenges, the goal of this work was to develop a technique for high-resolution free-breathing upper abdominal MRI at 7 T with a large field of view. Free-breathing 3D gradient-recalled echo (GRE) water-excited radial stack-of-stars data were acquired in seven healthy volunteers (five males/two females, body mass index: 19.6-24.8 kg/m 2 ) at 7 T using an eight-channel transceive array coil. Two volunteers were also examined at 3 T. In each volunteer, the liver and kidney regions were scanned in two separate acquisitions. To homogenize signal excitation, the time-interleaved acquisition of modes (TIAMO) method was used with personalized pairs of B 1 shims, based on a 23-s Cartesian fast low angle shot (FLASH) acquisition. Utilizing free-induction decay navigator signals, respiratory-gated images were reconstructed at a spatial resolution of 0.8 × 0.8 × 1.0 mm 3 . Two experienced radiologists rated the image quality and the impact of B 1 inhomogeneity and motion-related artifacts on multipoint scales. The images of all volunteers showcased effective water excitation and were accurately corrected for respiratory motion. The impact of B 1 inhomogeneity on image quality was minimal, underscoring the efficacy of the multitransmit TIAMO shim. The high spatial resolution allowed excellent depiction of small structures such as the adrenal glands, the proximal ureter, the diaphragm, and small blood vessels, although some streaking artifacts persisted in liver image data. In direct comparisons with 3 T performed for two volunteers, 7-T acquisitions demonstrated increases in signal-to-noise ratio of 77% and 58%. Overall, this work demonstrates the feasibility of free-breathing MRI in the upper abdomen at submillimeter spatial resolution at a magnetic field strength of 7 T., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Objectives: To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology., Methods: Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs., Results: Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively., Conclusion: USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma., Clinical Relevance Statement: Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy., Registration: The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 ., Key Points: LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers., Competing Interests: Compliance with ethical standards Guarantor The scientific guarantor of this publication is John J Hermans. Conflict of Interest The authors of this manuscript declare relationships with the following companies: Patrik Zámecnik declares to be a “Scientific Advisor to SPL Medical B.V.” and owner of shares of SPL Medical B.V. The other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry No complex statistical methods were necessary for this paper. Informed consent Written informed consent was obtained from all subjects (patients) in this study. Ethical approval Institutional Review Board approval was obtained from the Medical Research Ethics Committee Oost-Nederland. Study subjects or cohorts overlap No study subjects or cohorts have been previously reported. Methodology ProspectiveDiagnostic or prognostic studyPerformed at one institution, (© 2024. The Author(s).)

Background: This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment., Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center., Results: In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008)., Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors of this manuscript declare relationships with the following companies: C.J.A.P. has an advisory role for Nordic Pharma; SAS Analytics paid for traveling expenses G. Kazemier. This funding is not related to the current research. The remaining authors declare no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study evaluated the relationship between apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and tumor grades based on WHO, Adsay, and Kalimuthu classifications, using whole-mount pancreatectomy specimens. If glandular formation plays a key role in the degree of diffusion restriction, diffusion-weighted imaging could facilitate non-invasive grading of PDAC. A freehand region of interest (ROI) was drawn along tumor borders on the preoperative ADC map in each tumor-containing slice. Resection specimens were retrospectively graded according to WHO, Adsay, and Kalimuthu classifications and correlated with overall survival and the 10th percentile of whole-volume ADC values. Findings from 40 patients (23 male, median age 67) showed no correlation between ADC p10 values and WHO differentiation ( p = 0.050), Adsay grade ( p = 0.955), or Kalimuthu patterns ( p = 0.117). There was no association between ADC p10 and overall survival ( p = 0.082) and other clinicopathological variables. Survival was significantly lower for poor tumor differentiation ( p = 0.046) and non-glandular Kalimuthu patterns ( p = 0.016) and there was a trend towards inferior survival for Adsay G3 ( p = 0.090) after correction for age, tumor location, and stage. Preoperative ADC measurements for determining PDAC aggressiveness had limited clinical utility, as there was no correlation with histological parameters or overall survival in resectable PDAC.

CT perfusion (CTP) analysis is difficult to implement in clinical practice. Therefore, we investigated a novel semi-automated CTP AI biomarker and applied it to identify vascular phenotypes of pancreatic ductal adenocarcinoma (PDAC) and evaluate their association with overall survival (OS)., Methods: From January 2018 to November 2022, 107 PDAC patients were prospectively included, who needed to undergo CTP and a diagnostic contrast-enhanced CT (CECT). We developed a semi-automated CTP AI biomarker, through a process that involved deformable image registration, a deep learning segmentation model of tumor and pancreas parenchyma volume, and a trilinear non-parametric CTP curve model to extract the enhancement slope and peak enhancement in segmented tumors and pancreas. The biomarker was validated in terms of its use to predict vascular phenotypes and their association with OS. A receiver operating characteristic (ROC) analysis with five-fold cross-validation was performed. OS was assessed with Kaplan-Meier curves. Differences between phenotypes were tested using the Mann-Whitney U test., Results: The final analysis included 92 patients, in whom 20 tumors (21%) were visually isovascular. The AI biomarker effectively discriminated tumor types, and isovascular tumors showed higher enhancement slopes (2.9 Hounsfield unit HU/s vs. 2.0 HU/s, p < 0.001) and peak enhancement (70 HU vs. 47 HU, p < 0.001); the AUC was 0.86. The AI biomarker's vascular phenotype significantly differed in OS ( p < 0.01)., Conclusions: The AI biomarker offers a promising tool for robust CTP analysis. In PDAC, it can distinguish vascular phenotypes with significant OS prognostication.

Background: Due to centralization of pancreatic surgery, patients with pancreatic cancer are treated in pancreatic cancer networks, composed of referring hospitals (Spokes) and an expert center (Hub). This study aimed to investigate I) how pancreatic cancer networks are organized and II) evaluated by involved clinicians., Methods: Two online surveys were sent out between January-May 2022. Part I was sent out to the surgical network directors of all hospitals of the Dutch Pancreatic Cancer Group (DPCG). Part II was sent out to all involved clinicians in the Hubs-and-Spokes networks., Results: There was a large variety between the 15 networks concerning number of affiliated Spokes (1-7), annual pancreatoduodenectomies (20-129), and use of a service level agreement (SLA) (40%). More Spoke clinicians considered the Spoke the best location for diagnostic workup (74% vs 36%, P < 0.001). Only 30% of Spoke clinicians attended the Hubs multidisciplinary team meeting frequently. More Hub clinicians thought that exchange of patient information should be improved (37% vs 51%, P = 0.005)., Conclusion: A large variety in Dutch pancreatic cancer networks was observed concerning number of affiliated Spokes, use of SLAs, and logistic aspects of network care. Improvement of network care concern agreements on diagnostic workup, use of SLA, Spoke participation in the MDT, and patient information exchange., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM)., Methods: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated., Results: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95-0.96) and 0.80 (IQR 0.67-0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29-0.76) for tumor segmentation., Conclusions: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients., Relevance Statement: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist's workload and increasing accuracy and consistency., Key Points: • Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. • Automatic models can accurately segment tumors in patients with colorectal liver metastases. • Total tumor volume can be accurately calculated based on automatic segmentations., (© 2023. The Author(s).)

The preoperative prediction of resectability pancreatic ductal adenocarcinoma (PDAC) is challenging. This retrospective single-center study examined tumor and vessel radiomics to predict the resectability of PDAC in chemo-naïve patients. The tumor and adjacent arteries and veins were segmented in the portal-venous phase of contrast-enhanced CT scans, and radiomic features were extracted. Features were selected via stability and collinearity testing, and least absolute shrinkage and selection operator application (LASSO). Three models, using tumor features, vessel features, and a combination of both, were trained with the training set ( N = 86) to predict resectability. The results were validated with the test set ( N = 15) and compared to the multidisciplinary team's (MDT) performance. The vessel-features-only model performed best, with an AUC of 0.92 and sensitivity and specificity of 97% and 73%, respectively. Test set validation showed a sensitivity and specificity of 100% and 88%, respectively. The combined model was as good as the vessel model (AUC = 0.91), whereas the tumor model showed poor performance (AUC = 0.76). The MDT's prediction reached a sensitivity and specificity of 97% and 84% for the training set and 88% and 100% for the test set, respectively. Our clinician-independent vessel-based radiomics model can aid in predicting resectability and shows performance comparable to that of the MDT. With these encouraging results, improved, automated, and generalizable models can be developed that reduce workload and can be applied in non-expert hospitals.

Pigments in oil paint are bound by a complex oil polymer network that is prone to water-related chemical degradation. We use cryo-Fourier-transform infrared spectroscopy and differential scanning calorimetry to study how water distributes inside zinc white oil paint. By measuring water freezing and melting transitions, we show that water-saturated zinc white oil paint contains both liquid-like clustered water and nonclustered water. A comparison of titanium white paint and nonpigmented model systems indicates that water clustering happens near the pigment-polymer interface. The cluster size was estimated in the nanometer range based on the ice melting and freezing temperatures and on the position of the O-D vibration band. As liquid-like water can play a crucial role in the dissolution and transport of ions and molecules, understanding the factors that favor this phenomenon is essential for establishing safe conditions for the conservation of painted works of art., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study., Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons., Results: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0-12% and 27-62%, and for permanently unresectable CRLM between 3-40% and 6-47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients., Conclusion: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice., (© 2023. The Author(s).)

Purpose: To increase the effectiveness of respiratory gating in radial stack-of-stars MRI, particularly when imaging at high spatial resolutions or with multiple echoes., Methods: Free induction decay (FID) navigators were integrated into a three-dimensional gradient echo radial stack-of-stars pulse sequence. These navigators provided a motion signal with a high temporal resolution, which allowed single-spoke binning (SSB): each spoke at each phase encode step was sorted individually to the corresponding motion state of the respiratory signal. SSB was compared with spoke-angle binning (SAB), in which all phase encode steps of one projection angle were sorted without the use of additional navigator data. To illustrate the benefit of SSB over SAB, images of a motion phantom and of six free-breathing volunteers were reconstructed after motion-gating using either method. Image sharpness was quantitatively compared using image gradient entropies., Results: The proposed method resulted in sharper images of the motion phantom and free-breathing volunteers. Differences in gradient entropy were statistically significant (p = 0.03) in favor of SSB. The increased accuracy of motion-gating led to a decrease of streaking artifacts in motion-gated four-dimensional reconstructions. To consistently estimate respiratory signals from the FID-navigator data, specific types of gradient spoiler waveforms were required., Conclusion: SSB allowed high-resolution motion-corrected MR imaging, even when acquiring multiple gradient echo signals or large acquisition matrices, without sacrificing accuracy of motion-gating. SSB thus relieves restrictions on the choice of pulse sequence parameters, enabling the use of motion-gated radial stack-of-stars MRI in a broader domain of clinical applications., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM., Methods: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel. If no consensus existed among panel surgeons (i.e. same vote for (un)resectability of CRLM), conclusion was based on majority. The association of tumour biological (sidedness, synchronous CRLM, carcinoembryonic antigen and RAS/BRAF V600E mutation status) and technical anatomical factors with consensus among panel surgeons, secondary resectability and early recurrence (<6 months) without curative-intent repeat local treatment was analysed by uni- and pre-specified multivariable logistic regression., Results: After systemic treatment, 240 (50%) patients received complete local treatment of CRLM of which 75 (31%) patients experienced early recurrence without repeat local treatment. Higher number of CRLM (odds ratio 1.09 [95% confidence interval 1.03-1.15]) and age (odds ratio 1.03 [95% confidence interval 1.00-1.07]) were independently associated with early recurrence without repeat local treatment. In 138 (52%) patients, no consensus among panel surgeons was present prior to local treatment. Postoperative outcomes in patients with and without consensus were comparable., Conclusions: Almost a third of patients selected by an expert panel for secondary CRLM surgery following induction systemic treatment experience an early recurrence only amenable to palliative treatment. Number of CRLM and age, but no tumour biological factors are predictive, suggesting that until there are better biomarkers; resectability assessment remains primarily a technical anatomical decision., Competing Interests: Conflict of interest statement C.J.A.P. has an advisory role for Nordic Pharma. This funding is not related to the current research. The remaining authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Adequate TNM-staging is important to determine prognosis and treatment planning of duodenal adenocarcinoma. Although current guidelines advise contrast-enhanced CT (CECT) for staging of duodenal adenocarcinoma, literature about diagnostic tests is sparse., Methods: In this retrospective single-center cohort study, we analyzed the real life performance of routine CECT for TNM-staging and the assessment of resectability of duodenal adenocarcinoma. Intraoperative findings and pathological staging served as reference standard for resectability, T-, and N-staging. Biopsies, 18 FDG-PET-CT, and follow-up were used as the reference standard for M-staging., Results: Fifty-two consecutive patients with duodenal adenocarcinoma were included, 26 patients underwent resection. Half of the tumors were isodense to normal duodenum on CECT. The tumor was initially missed in 7/52 patients (13%) on CECT. The correct T-stage was assigned with CECT in 14/26 patients (54%), N-stage in 11/26 (42%), and the M-stage in 42/52 (81%). T-stage was underestimated in (27%). The sensitivity for detecting lymph node metastases was only 24%, specificity was 78%. Seventeen percent of patients had indeterminate liver or lung lesions on CECT. Surgery with curative intent was started in 32 patients, but six patients (19%) could not be resected due to unexpected local invasion or metastases., Conclusion: Radiologists and clinicians have to be aware that routine CECT is insufficient for staging and determining resectability in patients with duodenal adenocarcinoma. CECT underestimates T-stage and N-stage, and M-stage is often unclear, resulting in futile surgery in 19% of patients. Alternative strategies are required to improve staging of duodenal adenocarcinoma. We propose to combine multiphase hypotonic duodenography CT with MRI., (© 2022. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can provide additional diagnostic information compared to the limited accuracy of the current standard, contrast-enhanced CT (CECT). This systematic review evaluates CTP for diagnosis, grading, and treatment assessment of PDAC. The secondary goal is to provide an overview of scan protocols and perfusion models used for CTP in PDAC. The search strategy combined synonyms for 'CTP' and 'PDAC.' Pubmed, Embase, and Web of Science were systematically searched from January 2000 to December 2020 for studies using CTP to evaluate PDAC. The risk of bias was assessed using QUADAS-2. 607 abstracts were screened, of which 29 were selected for full-text eligibility. 21 studies were included in the final analysis with a total of 760 patients. All studies comparing PDAC with non-tumorous parenchyma found significant CTP-based differences in blood flow (BF) and blood volume (BV). Two studies found significant differences between pathological grades. Two other studies showed that BF could predict neoadjuvant treatment response. A wide variety in kinetic models and acquisition protocol was found among included studies. Quantitative CTP shows a potential benefit in PDAC diagnosis and can serve as a tool for pathological grading and treatment assessment; however, clinical evidence is still limited. To improve clinical use, standardized acquisition and reconstruction parameters are necessary for interchangeability of the perfusion parameters., (© 2021. The Author(s).)

Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morphologic response with gene mutation status, targeted therapy, and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 measurements. Materials and Methods Participants with initially unresectable CRLM receiving different systemic therapy regimens from the randomized, controlled CAIRO5 trial (NCT02162563) were included in this prospective imaging study. Three radiologists independently assessed morphologic tumor response on baseline and first follow-up CT scans according to previously published criteria. Two additional radiologists evaluated disagreement cases. Interobserver agreement was calculated by using Fleiss κ. On the basis of the majority of individual radiologic assessments, the final morphologic tumor response was determined. Finally, the relation of morphologic tumor response and clinical prognostic parameters was assessed. Results In total, 153 participants (median age, 63 years [IQR, 56-71]; 101 men) with 306 CT scans comprising 2192 CRLM were included. Morphologic assessment performed by the three radiologists yielded 86 (56%) agreement cases and 67 (44%) disagreement cases (including four major disagreement cases). Overall interobserver agreement between the panel radiologists on morphology groups and morphologic response categories was moderate (κ = 0.53, 95% CI: 0.48, 0.58 and κ = 0.54, 95% CI: 0.47, 0.60). Optimal morphologic response was particularly observed in patients treated with bevacizumab ( P = .001) and in patients with RAS/BRAF mutation ( P = .04). No evidence of a relationship between RECIST 1.1 and morphologic response was found ( P = .61). Conclusion Morphologic tumor response assessment following systemic therapy in participants with CRLM demonstrated considerable interobserver variability. Keywords: Tumor Response, Observer Performance, CT, Liver, Metastases, Oncology, Abdomen/Gastrointestinal Clinical trial registration no. NCT02162563 Supplemental material is available for this article. © RSNA, 2022.

Background: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology., Methods: In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens., Results: Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis., Conclusions: A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes.

Objectives: Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM)., Background: RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV., Methods: Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment., Results: A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of >40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease ( P = 0.015), while RECIST1.1 was not prognostic ( P = 0.821)., Conclusions: TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM., Competing Interests: C.J.A.P. has an advisory role for Nordic Pharma. This funding is not related to the current research. The remaining authors declare no potential conflicts of interest. The CAIRO5 study is supported by unrestricted scientific grants from Roche and Amgen. The funders had no role in the design, conduct, and submission of the study, or in the decision to submit the manuscript for publication., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) or biopsy (FNB) to diagnose lesions in the gastrointestinal tract is common. Demand for histology sampling to identify treatment-specific targets is increasing. Various core biopsy FNB needles to obtain tissue for histology are currently available, however, with variable (37-97%) histology yields. In this multicenter study, we evaluated performance, safety, and user experience of a novel device (the puncture biopsy forceps (PBF) needle). Twenty-four procedures with the PBF needle were performed in 24 patients with a suspected pancreatic lesion ( n = 10), subepithelial lesion ( n = 10), lymph node ( n = 3), or pararectal mass ( n = 1). In 20/24 (83%) procedures, the PBF needle yielded sufficient material for interpretation (sample adequacy). In 17/24 (71%), a correct diagnosis was made with the material from the PBF needle (diagnostic accuracy). All participating endoscopists experienced a learning curve. (Per)procedural technical issues occurred in four cases (17%), but there were no adverse events. The PBF needle is a safe and potentially useful device to obtain an EUS-guided biopsy specimen. As the design of the PBF needle is different to core biopsy FNB needles, specific training will likely further improve the performance of the PBF needle. Furthermore, the design of the needle needs further improvement to make it more robust in clinical practice.

Background: Over the past decades, health care services for pancreatic surgery were reorganized. Volume norms were applied with the result that only a limited number of expert centers perform pancreatic surgery. As a result of this centralization of pancreatic surgery, the patient journey of patients with pancreatic tumors has become multi-institutional. To illustrate, patients are referred to a center of expertise for pancreatic surgery whereas other parts of pancreatic care, such as chemotherapy, take place in local hospitals. This fragmentation of health care services could affect continuity of care (COC). The aim of this study was to assess COC perceived by patients in a pancreatic care network and investigate correlations with patient-and care-related characteristics., Methods: This is a pilot study in which patients with (pre) malignant pancreatic tumors discussed in a multidisciplinary tumor board in a Dutch tertiary hospital were asked to participate. Patients were asked to fill out the Nijmegen Continuity of Care-questionnaire (NCQ) (5-point Likert scale). Additionally, their patient-and care-related data were retrieved from medical records. Correlations of NCQ score and patient-and care-related characteristics were calculated with Spearman's correlation coefficient., Results: In total, 44 patients were included (92% response rate). Pancreatic cancer was the predominant diagnosis (32%). Forty percent received a repetition of diagnostic investigations in the tertiary hospital. Mean scores for personal continuity were 3.55 ± 0.74 for GP, 3.29 ± 0.91 for the specialist and 3.43 ± 0.65 for collaboration between GPs and specialists. Overall COC was scored with a mean 3.38 ± 0.72. No significant correlations were observed between NCQ score and certain patient-or care-related characteristics., Conclusion: Continuity of care perceived by patients with pancreatic tumors was scored as moderate. This outcome supports the need to improve continuity of care within multi-institutional pancreatic care networks.

Background: Preoperative differentiation between neoplastic and nonneoplastic gallbladder polyps, and the subsequent indication for cholecystectomy remains a clinical dilemma. The current 1 cm size threshold for neoplasia is unspecific. The aim of this study was to improve diagnostic work-up for gallbladder polyps using sonographic and MRI characteristics of neoplastic and nonneoplastic polyps., Methods: A prospective, exploratory study including patients undergoing cholecystectomy for gallbladder polyp(s) was conducted. Patients underwent targeted transabdominal ultrasound (TAUS) and MRI. Outcomes were sensitivity and specificity for polyp diagnosis, and the radiological characteristics of neoplastic and nonneoplastic polyp types. Histopathology after cholecystectomy was used as reference standard., Results: Histopathology demonstrated gallbladder polyps in 20/27 patients (74%): 14 cholesterol polyps, three adenomyomatosis, two adenomas and one gastric heterotopia. Sensitivity of polyp identification were 72% (routine TAUS) and 86% (targeted TAUS and MRI). Both adenomas were identified as neoplastic on targeted TAUS and MRI. Sonographic presentation as multiple, pedunculated polyps, either heterogeneous or with hyperechoic foci, or as single polyps containing cysts were limited to nonneoplastic polyps. On MRI hyperintense polyps on T1-weighted image were cholesterol polyps. An adenoma with high-grade dysplasia showed foci of decreased ADC values. We propose a checklist for polyp evaluation by targeted TAUS and a flowchart for radiological work-up of gallbladder polyps., Conclusions: The presented checklist and flowchart could aid diagnostic work-up for gallbladder polyps compared to current routine ultrasound, by elimination of nonneoplastic polyps and ultimately improve treatment decision for patients with gallbladder polyps., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Since current studies on locally advanced pancreatic cancer (LAPC) mainly report from single, high-volume centers, it is unclear if outcomes can be translated to daily clinical practice. This study provides treatment strategies and clinical outcomes within a multicenter cohort of unselected patients with LAPC., Materials and Methods: Consecutive patients with LAPC according to Dutch Pancreatic Cancer Group criteria, were prospectively included in 14 centers from April 2015 until December 2017. A centralized expert panel reviewed response according to RECIST v1.1 and potential surgical resectability. Primary outcome was median overall survival (mOS), stratified for primary treatment strategy., Results: Overall, 422 patients were included, of whom 77% (n = 326) received chemotherapy. The majority started with FOLFIRINOX (77%, 252/326) with a median of six cycles (IQR 4-10). Gemcitabine monotherapy was given to 13% (41/326) of patients and nab-paclitaxel/gemcitabine to 10% (33/326), with a median of two (IQR 3-5) and three (IQR 3-5) cycles respectively. The mOS of the entire cohort was 10 months (95%CI 9-11). In patients treated with FOLFIRINOX, gemcitabine monotherapy, or nab-paclitaxel/gemcitabine, mOS was 14 (95%CI 13-15), 9 (95%CI 8-10), and 9 months (95%CI 8-10), respectively. A resection was performed in 13% (32/252) of patients after FOLFIRINOX, resulting in a mOS of 23 months (95%CI 12-34)., Conclusion: This multicenter unselected cohort of patients with LAPC resulted in a 14 month mOS and a 13% resection rate after FOLFIRINOX. These data put previous results in perspective, enable us to inform patients with more accurate survival numbers and will support decision-making in clinical practice., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Monoalkyltin(iv) complexes are well-known catalysts for esterification reactions and polyester formation, yet the mode of operation of these Lewis acidic complexes is still unknown. Here, we report on mechanistic studies of n -butylstannoic acid in stoichiometric and catalytic reactions, analyzed by NMR, IR and MS techniques. While the chemistry of n -butyltin(iv) carboxylates is dominated by formation of multinuclear tin assemblies, we found that under catalytically relevant conditions only monomeric n -BuSn(OAc) 3 and dimeric ( n -BuSnOAc 2 OEt) 2 are present. Density functional theory (DFT) calculations provide support for a mononuclear mechanism, where n -BuSn(OAc) 3 and dimeric ( n -BuSnOAc 2 OEt) 2 are regarded as off-cycle species, and suggest that carbon-oxygen bond breaking is the rate-determining step., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Introduction: Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM., Material and Methods: Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation., Results: Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21-54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48-79) and 30 ml/min/100ml (95% CI 22-38). Mean PI was 68% (95% CI 62-73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found., Conclusion: In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM., Competing Interests: The authors have declared that no competing interests exist.

Background: The primary aim was to assess the diagnostic accuracy of routine ultrasound assessment for gallbladder polyps. The secondary aim was to identify the characteristics that differentiate neoplastic polyps from nonneoplastic polyps., Methods: A total of 156 patients with histopathologically proven gallbladder polyps in 4 Dutch hospitals between 2003 and 2013 were included. Sensitivity and specificity of ultrasound for polyp size, number of polyps, and polyp type were assessed using histopathological findings as a reference standard. In addition, diagnostic accuracy of sonographic size ≥1 cm for neoplasia was assessed. Subgroup analysis for patients with polyps as primary indication for cholecystectomy was performed. The sonographic polyp characteristics on preoperative routine ultrasound were described., Results: Fifty-six percent of gallbladder polyps were preoperatively identified on ultrasound, of which 31% were neoplastic. Sensitivity and specificity of ultrasound to estimate polyp size were 93 and 43% (subgroup; 92 and 33%). Sensitivity and specificity of sonographic polyp size ≥1 cm for neoplasia were 86 and 32% (subgroup; 94 and 26%). No specific sonographic characteristics for neoplastic polyps could be established due to lack of reporting., Conclusion: Routine ultrasound assessment of polyps is associated with overestimation of polyp size and low specificity of sonographic size ≥1 cm for neoplasia, which contributes to surgical overtreatment of nonneoplastic polyps., (© 2020 The Author(s). Published by S. Karger AG, Basel.)

Background: Artifacts caused by respiratory motion or ventilation-induced chest movements are a major problem for thoracic MRI, as they can obscure important anatomical structures such as lymph node metastases. We compared image quality of routine breathhold with intermittent apnea during controlled mechanical ventilation of patients under general anesthesia as the ideal situation without respiratory motion in the detection and characterization of regional lymph nodes in esophageal cancer., Methods: In this prospective study, 10 patients treated for esophageal cancer underwent ultrasmall superparamagnetic iron oxide (USPIO) enhanced MRI scans. Before neoadjuvant therapy, MRI scans were acquired with a routine breathhold technique. After neoadjuvant therapy, patients were scanned under general anesthesia immediately prior to surgery with controlled mechanical ventilation. The image quality was compared using a Likert scale questionnaire based on visibility of anatomical structures and image artifacts., Results: MRI with controlled mechanical ventilation and prolonged controlled apnea of 4 min was safe and feasible. All cardio-respiratory monitoring parameters remained stable during the apnea phases. Mediastinal and upper abdominal lymph nodes down to 2 mm in size could be visualized with all sequences. All image quality criteria, including visibility of thoracic structures and regional lymph nodes were scored higher using the controlled ventilation sequences compared to the routine breathhold phase., Conclusion: USPIO-enhanced MRI with controlled mechanical ventilation is superior to routine breathhold MRI in visualizing lymph nodes, which warrants new motion reduction techniques to use MRI for the detection of lymph node metastases in patients with esophageal cancer., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: At the time of surgery, approximately 10-20% of the patients with pancreatic cancer are considered unresectable because of unexpected liver metastasis, peritoneal carcinomatosis or locally advanced disease. This leads to futile surgical treatment with all the associated morbidity, mortality and costs. More than 50% of all liver metastases develop in the first six months postoperatively. These (subcentimeter) liver metastases are most likely already present at the time of diagnosis and have not been identified pre-operatively, due to the poor sensitivity of routine preoperative contrast-enhanced CT (CECT)., Methods: The DIA-PANC study is a prospective, international, multicenter, diagnostic cohort study investigating diffusion-weighted, contrast-enhanced MRI for the detection of liver metastases in patients with all stages of pancreatic cancer. Indeterminate or malignant liver lesions on MRI will be further investigated histopathologically. For patients with suspected liver lesions without histopathological proof, follow up imaging with paired CT and MRI at 3-, 6- and 12-months will serve as an alternative reference standard., Discussion: The DIA-PANC trial is expected to report high-level evidence of the diagnostic accuracy of MRI for the detection of liver metastases, resulting in significant value for clinical decision making, guideline development and improved stratification for treatment strategies and future trials. Furthermore, DIA-PANC will contribute to our knowledge of liver metastases regarding incidence, imaging characteristics, their number and extent, and their change in time with or without treatment. It will enhance the worldwide implementation of MRI and consequently improve personalized treatment of patients with suspected pancreatic ductal adenocarcinoma., Trial Registration: ClinicalTrials.gov Identifier: NCT03469726 . Registered on March 19th 2018 - Retrospectively registered.

Medullary pancreatic carcinoma (MPC) is a rare histological variant of pancreatic ductal adenocarcinoma (PDAC). Because of its rarity, data on the molecular background of MPC are limited. Previous studies have shown that a subset of MPCs is microsatellite instable due to mismatch repair deficiency. Here, we present a unique case of a female patient in her 60s who is a long-term survivor after surgery for pancreatic cancer. The patient had a microsatellite stable MPC with a somatic mutation of the polymerase epsilon gene (POLE). Both microsatellite instable and POLE-mutated cancers are usually associated with high tumor mutational burden and antigen load, resulting in a prominent antitumor immune response and overall better survival. The current case illustrates that, in addition to mismatch repair deficiency, MPC can develop because of a somatic POLE mutation, resulting in a tumor with a high tumor mutational burden and leading to a better prognosis compared with conventional PDAC. This new finding may have important implications in the management of patients with MPC and calls for further studies on the role of POLE in PDAC.

The exposure of oil paintings to organic solvents for varnish removal or to water for the removal of surface dirt can affect the chemical and physical properties of oil paint in an undesired way. Solvents can temporarily plasticise and swell the polymerised oil paint binding medium, enhancing both the thermal mobility and mechanical displacement of pigments embedded in this film. The enhancement of these microscopic motions can affect both the chemical and physical stability of the object as a whole. In order to minimise solvent exposure during cleaning, an analytical method that can quantitatively measure the microscopic motions induced by solvent uptake, is required first. In this study, we use Fourier Transform Laser Speckle Imaging (FT-LSI) and a newly developed portable FT-LSI setup as highly resolved motion detection instruments. We employ FT-LSI to probe pigment motion, with high spatiotemporal resolution, as a proxy for the destabilising effects of cleaning solvents. In this way, we can study solvent diffusion and evaporation rates and the total solvent retention time. In addition, qualitative spatial information on the spreading and homogeneity of the applied solvent is obtained. We study mobility in paint films caused by air humidity, spreading of solvents as a result of several cleaning methods and the protective capabilities of varnish. Our results show that FT-LSI is a powerful technique for the study of solvent penetration during oil paint cleaning and has a high potential for future use in the conservation studio.

The increasing incidence of pancreatic cancer will make it the second deadliest cancer in 2030. Imaging based early diagnosis and image guided treatment are emerging potential solutions. Artificial intelligence (AI) can help provide and improve widespread diagnostic expertise and accurate interventional image interpretation. Accurate segmentation of the pancreas is essential to create annotated data sets to train AI, and for computer assisted interventional guidance. Automated deep learning segmentation performance in pancreas computed tomography (CT) imaging is low due to poor grey value contrast and complex anatomy. A good solution seemed a recent interactive deep learning segmentation framework for brain CT that helped strongly improve initial automated segmentation with minimal user input. This method yielded no satisfactory results for pancreas CT, possibly due to a sub-optimal neural network architecture. We hypothesize that a state-of-the-art U-net neural network architecture is better because it can produce a better initial segmentation and is likely to be extended to work in a similar interactive approach. We implemented the existing interactive method, iFCN, and developed an interactive version of U-net method we call iUnet. The iUnet is fully trained to produce the best possible initial segmentation. In interactive mode it is additionally trained on a partial set of layers on user generated scribbles. We compare initial segmentation performance of iFCN and iUnet on a 100CT dataset using dice similarity coefficient analysis. Secondly, we assessed the performance gain in interactive use with three observers on segmentation quality and time. Average automated baseline performance was 78% (iUnet) versus 72% (FCN). Manual and semi-automatic segmentation performance was: 87% in 15 min. for manual, and 86% in 8 min. for iUNet. We conclude that iUnet provides a better baseline than iFCN and can reach expert manual performance significantly faster than manual segmentation in case of pancreas CT. Our novel iUnet architecture is modality and organ agnostic and can be a potential novel solution for semi-automatic medical imaging segmentation in general.

Although the concentration of carboxylic acid (COOH) groups is crucial to understand oil paint chemistry, analytical challenges hindered COOH quantification in complex polymerised oil samples thus far. The concentration of COOH groups is important in understanding oil paint degradation because it drives the breakdown of reactive inorganic pigments to dissolve in the oil network and form metal carboxylates. The metal ions in such an ionomeric polymer network can exchange with saturated fatty acids to form crystalline metal soaps (metal complexes of saturated fatty acids), leading to serious problems in many paintings worldwide. We developed two methods based on ATR-FTIR spectroscopy to accurately estimate the COOH concentration in artificially aged oil paint models. Using tailored model systems composed of linseed oil, ZnO and inert filler pigments, these dried oil paints were found to contain one COOH group per triacylglycerol unit. Model systems based on a mixture of long chain alcohols showed that the calculated COOH concentration originates from side chain autoxidation at low relative humidity (RH). The influence of increasing RH and ZnO concentration on COOH formation was studied and high relative humidity conditions were shown to promote the formation of COOH groups. No significant ester hydrolysis was found under the conditions studied. Our results show the potential of quantitative analysis of oil paint model systems for aiding careful (re)evaluation of conservation strategies., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: The aim of this study is to collect the best available evidence for diagnostic modalities, frequency, and duration of surveillance after resection for pancreatic ductal adenocarcinoma (PDAC)., Methods: PDAC guidelines published after 2015 were collected. Furthermore, a systematic search of the literature on postoperative surveillance was performed in PubMed and Embase from 2000 to 2019. Articles comparing different diagnostic modalities and frequencies of postoperative surveillance in PDAC patients with regard to survival, quality of life, morbidity and cost-effectiveness were selected., Results: The literature search resulted in 570 articles. A total of seven guidelines and twelve original clinical studies were eventually evaluated. PDAC guidelines increasingly recommend a combination of tumor marker testing and computed tomography (CT) imaging every three to six months during the first two years after resection. These guidelines are, however, based on expert opinion and other low-level evidence. Prospective studies comparing different surveillance strategies are lacking. According to recent studies, surveillance with tumor markers and imaging at regular intervals results in the detection of PDAC recurrence before the onset of symptoms and more frequent administration of further therapy, such as chemotherapy or radiotherapy., Conclusion: Current evidence for recurrence-focused surveillance after PDAC resection is limited and contradictory. Consequently, recommendations on surveillance are conflicting. To define the clinical merit of recurrence-focused surveillance, patients who are most likely to benefit from early detection and treatment of PDAC recurrence need to be identified. To this purpose, well-designed prospective studies are needed, accounting for both economical and psychosocial implications of surveillance., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The molecular structure around metal ions in polymer materials has puzzled researchers for decades. This question has acquired new relevance with the discovery that aged oil paint binders can adopt an ionomer structure when metal ions leached from pigments bind to carboxylate groups on the polymerized oil network. The characteristics of the metal-polymer structure are expected to have important consequences for the rate of oil paint degradation reactions such as metal soap formation and oil hydrolysis. Here, we use two-dimensional infrared (2D-IR) spectroscopy to demonstrate that zinc carboxylates formed in paint films containing zinc white pigment adopt either a coordination chain- or an oxo-type cluster structure. Moreover, it was found that the presence of water governs the relative concentration of these two types of zinc carboxylate coordination. The results pave the way for a molecular approach to paintings conservation and the application of 2D-IR spectroscopy to the study of polymer structure.

Purpose: To explore the value of gadolinium-enhanced MRI combined with diffusion-weighted MRI (Gd-enhanced MRI with DWI) in addition to contrast-enhanced CT (CECT) for detection of synchronous liver metastases for potentially resectable pancreatic cancer., Methods: By means of a retrospective cohort study we included patients with potentially resectable pancreatic cancer on CECT, who underwent Gd-enhanced MRI with DWI between January 2012 and December 2016. A single observer evaluated MRI and CT and was blinded to imaging, pathology, and surgery reports. Liver lesions were scored in both modalities, using a 3-point scale: 1-benign, 2-indeterminate, 3- malignant (i.e., metastasis). The primary outcome parameters were the presence of liver metastases on Gd-enhanced MRI with DWI and the sensitivity of Gd-enhanced MRI with DWI for synchronous liver metastases., Results: We included 66 patients (42 men, 24 women; median age 65 years, range 36-82 years). In 19 patients, liver metastases were present, which were confirmed by histopathology (n = 12), 18 FDG-PET (n = 6), or surgical inspection (n = 1). Gd-enhanced MRI with DWI showed metastases in 16/19 patients (24%), which resulted in a sensitivity of 84% (95% CI 60-97%). Contrast-enhanced MRI showed 156 and DWI 397 metastases (p = 0.051), and 339 were particularly small (< 5 mm)., Conclusions: In this study, Gd-enhanced MRI with DWI detected synchronous liver metastases in 24% of patients with potentially resectable pancreatic cancer on CECT with a sensitivity of 84%. Diffusion-weighted MRI showed a greater number of metastases than any other sequence, particularly small metastases (< 5 mm).

Purpose: Metabolic parameters are increasingly being used to characterize tumors. Motion artifacts due to patient respiration introduce uncertainties in quantification of metabolic parameters during positron emission tomography (PET) image acquisition. The present study investigates the impact of amplitude-based optimal respiratory gating (ORG) on quantification of PET-derived image features in patients with pancreatic ductal adenocarcinoma (PDAC), in correlation with overall survival (OS)., Methods: Sixty-nine patients with histologically proven primary PDAC underwent 2'-deoxy-2'-[ 18 F]fluoroglucose ([ 18 F]FDG) PET/CT imaging during diagnostic work-up. Standard image acquisition and reconstruction was performed in accordance with the EANM guidelines and ORG images were reconstructed with a duty cycle of 35%. PET-derived image features, including standard parameters, first- and second-order texture features, were calculated from the standard and corresponding ORG images, and correlation with OS was assessed., Results: ORG significantly impacts the quantification of nearly all features; values of single-voxel parameters (e.g., SUV max ) showed a wider range, volume-based parameters (e.g., SUV mean ) were reduced, and texture features were significantly changed. After correction for motion artifacts using ORG, some features that describe intra-tumoral heterogeneity were more strongly correlated to OS., Conclusions: Correction for respiratory motion artifacts using ORG impacts the quantification of metabolic parameters in PDAC lesions. The correlation of metabolic parameters with OS was significantly affected, in particular parameters that describe intra-tumor heterogeneity. Therefore, interpretation of single-voxel or average metabolic parameters in relation to clinical outcome should be done cautiously. Furthermore, ORG is a valuable tool to improve quantification of intra-tumoral heterogeneity in PDAC.

Background: Lymph node metastases (LNM) are an ominous prognostic factor in gallbladder cancer (GBC) and, when present, should preclude surgery. However, uncertainty remains regarding the optimal imaging modality for pre-operative detection of LNM and international guidelines vary in their recommendations. The purpose of this study was to systematically review the diagnostic accuracy of computed tomography (CT) versus magnetic resonance imaging (MRI) in the detection of LNM of GBC., Methods: A literature search of studies published until November 2017 concerning the diagnostic accuracy of CT or MRI regarding the detection of LNM in GBC was performed. Data extraction and risk of bias assessment was performed independently by two reviewers. The sensitivity of CT and MRI in the detection of LNM was reviewed. Additionally, estimated summary sensitivity, specificity and diagnostic accuracy of MRI were calculated in a patient based meta-analysis., Results: Nine studies including 292 patients were included for narrative synthesis and 5 studies including 158 patients were selected for meta-analysis. Sensitivity of CT ranged from 0.25 to 0.93. Estimated summary diagnostic accuracy parameters of MRI were as follows: sensitivity 0.75 (95% CI 0.6 - 0.85), specificity 0.83 (95% CI 0.74 - 0.90), LR + 4.52 (95% CI 2.55-6.48) and LR- 0.3 (95% CI 0.15 - 0.45). Small (<10 mm) LNM were most frequently undetected on pre-operative imaging. Due to a lack of data, no subgroup analysis comparing the diagnostic accuracy of CT versus MRI could be performed., Conclusion: The value of current imaging strategies for the pre-operative assessment of nodal status in GBC remains unclear, especially regarding the detection of small LNM. Additional research is warranted in order to establish uniformity in international guidelines, improve pre-operative nodal staging and to prevent futile surgery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

[This corrects the article DOI: 10.1021/acs.macromol.8b00890.].

In the restoration of paintings, solvent diffusion and swelling of polymeric oil paint binding media are important factors to consider. Common cleaning methods with organic solvents or aqueous solutions could lead to undesirable physicochemical changes in the paint in the long term, though the extent of this effect is not yet clear. We used tailored nonporous model systems for aged oil paint to measure paint swelling and solvent diffusion for a wide range of relevant solvents. Using dynamic mechanical analysis (DMA), the glass transition temperature of our model systems was found to be close to room temperature. Subsequently, with a custom sample cell and time-dependent attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, we were able to accurately track swelling and diffusion processes in the polymer films. To quantify the spectroscopic data, we developed a model that completely describes the solvent migration process, including significant film swelling and non-Fickian solvent diffusion. The relation between solvent properties, the diffusion coefficient, and the swelling capacity proved to be rather complex and could not be explained using a single solvent parameter. However, it was found that strongly swelling solvents generally diffuse faster than weakly swelling solvents and that pigmentation does not significantly influence solvent diffusion. These results contribute to a better understanding of transport phenomena in paintings and support the development of improved paint restoration strategies., Competing Interests: The authors declare no competing financial interest.

The formation of metal soaps (metal complexes of saturated fatty acids) is a serious problem affecting the appearance and structural integrity of many oil paintings. Tailored model systems for aged oil paint and time-dependent attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy were used to study the diffusion of palmitic acid and subsequent metal soap crystallization. The simultaneous presence of free saturated fatty acids and polymer-bound metal carboxylates leads to rapid metal soap crystallization, following a complex mechanism that involves both acid and metal diffusion. Solvent flow, water, and pigments all enhance metal soap crystallization in the model systems. These results contribute to the development of paint cleaning strategies, a better understanding of oil paint degradation, and highlight the potential of time-dependent ATR-FTIR spectroscopy for studying dynamic processes in polymer films., (© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Objectives: Severe acute pancreatitis is associated with peripancreatic morphologic changes as seen on imaging. Uniform communication regarding these morphologic findings is crucial for accurate diagnosis and treatment. For the original 1992 Atlanta classification, interobserver agreement is poor. We hypothesized that for the revised Atlanta classification, interobserver agreement will be better., Methods: An international, interobserver agreement study was performed among expert and nonexpert radiologists (n = 14), surgeons (n = 15), and gastroenterologists (n = 8). Representative computed tomographies of all stages of acute pancreatitis were selected from 55 patients and were assessed according to the revised Atlanta classification. The interobserver agreement was calculated among all reviewers and subgroups, that is, expert and nonexpert reviewers; interobserver agreement was defined as poor (≤0.20), fair (0.21-0.40), moderate (0.41-0.60), good (0.61-0.80), or very good (0.81-1.00)., Results: Interobserver agreement among all reviewers was good (0.75 [standard deviation, 0.21]) for describing the type of acute pancreatitis and good (0.62 [standard deviation, 0.19]) for the type of peripancreatic collection. Expert radiologists showed the best and nonexpert clinicians the lowest interobserver agreement., Conclusions: Interobserver agreement was good for the revised Atlanta classification, supporting the importance for widespread adaption of this revised classification for clinical and research communications.

Objectives: Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP., Methods: We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging)., Results: We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency., Conclusions: In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.

Objective: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI., Design: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion., Results: Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size., Conclusions: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The formation and crystallization of metal soaps in oil paint layers is an important issue in the conservation of oil paintings. The chemical reactions and physical processes that are involved in releasing metal ions from pigments and fatty acids from the oil binder to form crystalline metal soap deposits have so far remained poorly understood. We have used a combination of differential scanning calorimetry (DSC) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) on model mixtures of palmitic acid, lead palmitate or zinc palmitate and linseed oil to study the transition from amorphous material to crystalline fatty acid or metal soap. This transition forms the final stage in the cascade of processes leading to metal soap-related oil paint degradation. Palmitic acid as well as the metal soaps showed nearly ideal solubility behavior. However, it was found that, near room temperature, both lead and zinc palmitate are practically insoluble in both liquid and partially polymerized linseed oil. Interestingly, the rate of metal soap and fatty acid crystallization decreased rapidly with the degree of linseed oil polymerization, possibly leading to systems where metal soaps are kinetically trapped in a semi-crystalline state. To explain the various morphologies of metal soap aggregates observed in oil paint layers, it is proposed that factors affecting the probability of crystal nucleation and the rate of crystal growth play a crucial role, like exposure to heat or cleaning solvents and the presence of microcracks.

Four patients diagnosed with haematological malignancies developed an isolated hyperbilirubinaemia following cytarabine- and anthracycline-based chemotherapy. The clinical picture was consistent with acalculous cholecystitis, but ultrasonography did not show the typical gallbladder wall thickening. All patients suffered from severe mucositis with neutropenic enterocolitis. We hypothesise that damage of the mucosa of the gallbladder induced by chemotherapy results in hyperpermeability of the mucosal barrier with bile leakage and isolated hyperbilirubinaemia., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: There is strong evidence for an association between obesity and esophageal adenocarcinoma (EAC). This study investigated the association between directly measured visceral adipose tissue and the risk of EAC., Methods: In a case-control setting, we measured visceral adipose tissue in patients with EAC and healthy controls. Visceral adipose tissue was determined by abdominal CT. Exclusion criteria were uninterpretable CT scans and severe comorbidity. Controls were healthy volunteers undergoing screening CT colonography. Cross-sectional areas of visceral and subcutaneous adipose tissues were measured in cm(2) at L3/L4. Values of adipose tissue of EAC patients were extrapolated to stage 0 and compared to controls. The association between visceral adipose tissue and EAC was calculated with least-squares regression, adjusted for age, sex and TNM stage., Results: We included 175 EAC patients and 251 controls. While body mass index was similar in EAC patients (26.1 kg/m(2)) and controls (26.2 kg/m(2)), visceral adipose tissue was significantly higher in EAC patients at stage 0 than in controls (276 vs. 231 cm(2); p = 0.015). Regarding subcutaneous adipose tissue, there was no difference., Conclusions: Patients with EAC have significantly higher visceral adipose tissue than healthy controls. Visceral adipose tissue is a risk factor in the development of EAC and seems to be more important than obesity alone.

Significance: Stroke, a leading cause of death and disability, poses a substantial burden for patients, relatives, and our healthcare systems. Only one drug is approved for treating stroke, and more than 30 contraindications exclude its use in 90% of all patients. Thus, new treatments are urgently needed. In this review, we discuss oxidative stress as a pathomechanism of poststroke neurodegeneration and the inhibition of its source, type 4 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX4), as a conceptual breakthrough in stroke therapy., Recent Advances: Among potential sources of reactive oxygen species (ROS), the NOXes stand out as the only enzyme family that is solely dedicated to forming ROS. In rodents, three cerebrovascular NOXes exist: the superoxide-forming NOX1 and 2 and the hydrogen peroxide-forming NOX4. Studies using NOX1 knockout mice gave conflicting results, which overall do not point to a role for this isoform. Several reports find NOX2 to be relevant in stroke, albeit to variable and moderate degrees. In our hands, NOX4 is, by far, the major source of oxidative stress and neurodegeneration on ischemic stroke., Critical Issues: We critically discuss the tools that have been used to validate the roles of NOX in stroke. We also highlight the relevance of different animal models and the need for advanced quality control in preclinical stroke research., Future Directions: The development of isoform-specific NOX inhibitors presents a precious tool for further clarifying the role and drugability of NOX homologues. This could pave the avenue for the first clinically effective neuroprotectant applied poststroke, and even beyond this, stroke could provide a proof of principle for antioxidative stress therapy.