Reproducible Radiomics Features from Multi-MRI-Scanner Test-Retest-Study: Influence on Performance and Generalizability of Models.

BACKGROUND: Radiomics models trained on data from one center typically show a decline of performance when applied to data from external centers, hindering their introduction into large-scale clinical practice. Current expert recommendations suggest to use only reproducible radiomics features isolated by multiscanner test-retest experiments, which might help to overcome the problem of limited generalizability to external data. PURPOSE: To evaluate the influence of using only a subset of robust radiomics features, defined in a prior in vivo multi-MRI-scanner test-retest-study, on the performance and generalizability of radiomics models. STUDY TYPE: Retrospective. POPULATION: Patients with monoclonal plasma cell disorders. Training set (117 MRIs from center 1); internal test set (42 MRIs from center 1); external test set (143 MRIs from center 2-8). FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T; T1-weighted turbo spin echo. ASSESSMENT: The task for the radiomics models was to predict plasma cell infiltration, determined by bone marrow biopsy, noninvasively from MRI. Radiomics machine learning models, including linear regressor, support vector regressor (SVR), and random forest regressor (RFR), were trained on data from center 1, using either all radiomics features, or using only reproducible radiomics features. Models were tested on an internal (center 1) and a multicentric external data set (center 2-8). STATISTICAL TESTS: Pearson correlation coefficient r and mean absolute error (MAE) between predicted and actual plasma cell infiltration. Fisher's z-transformation, Wilcoxon signed-rank test, Wilcoxon rank-sum test; significance level P < 0.05. RESULTS: When using only reproducible features compared with all features, the performance of the SVR on the external test set significantly improved (r = 0.43 vs. r = 0.18 and MAE = 22.6 vs. MAE = 28.2). For the RFR, the performance on the external test set deteriorated when using only reproducible instead of all radiomics features (r = 0.33 vs. r = 0.44, P = 0.29 and MAE = 21.9 vs. MAE = 20.5, P = 0.10). CONCLUSION: Using only reproducible radiomics features improves the external performance of some, but not all machine learning models, and did not automatically lead to an improvement of the external performance of the overall best radiomics model. TECHNICAL EFFICACY: Stage 2.

Potential of ChatGPT and GPT-4 for Data Mining of Free-Text CT Reports on Lung Cancer.

Background The latest large language models (LLMs) solve unseen problems via user-defined text prompts without the need for retraining, offering potentially more efficient information extraction from free-text medical records than manual annotation. Purpose To compare the performance of the LLMs ChatGPT and GPT-4 in data mining and labeling oncologic phenotypes from free-text CT reports on lung cancer by using user-defined prompts. Materials and Methods This retrospective study included patients who underwent lung cancer follow-up CT between September 2021 and March 2023. A subset of 25 reports was reserved for prompt engineering to instruct the LLMs in extracting lesion diameters, labeling metastatic disease, and assessing oncologic progression. This output was fed into a rule-based natural language processing pipeline to match ground truth annotations from four radiologists and derive performance metrics. The oncologic reasoning of LLMs was rated on a five-point Likert scale for factual correctness and accuracy. The occurrence of confabulations was recorded. Statistical analyses included Wilcoxon signed rank and McNemar tests. Results On 424 CT reports from 424 patients (mean age, 65 years ± 11 [SD]; 265 male), GPT-4 outperformed ChatGPT in extracting lesion parameters (98.6% vs 84.0%, P < .001), resulting in 96% correctly mined reports (vs 67% for ChatGPT, P < .001). GPT-4 achieved higher accuracy in identification of metastatic disease (98.1% [95% CI: 97.7, 98.5] vs 90.3% [95% CI: 89.4, 91.0]) and higher performance in generating correct labels for oncologic progression (F1 score, 0.96 [95% CI: 0.94, 0.98] vs 0.91 [95% CI: 0.89, 0.94]) (both P < .001). In oncologic reasoning, GPT-4 had higher Likert scale scores for factual correctness (4.3 vs 3.9) and accuracy (4.4 vs 3.3), with a lower rate of confabulation (1.7% vs 13.7%) than ChatGPT (all P < .001). Conclusion When using user-defined prompts, GPT-4 outperformed ChatGPT in extracting oncologic phenotypes from free-text CT reports on lung cancer and demonstrated better oncologic reasoning with fewer confabulations. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Hafezi-Nejad and Trivedi in this issue.

Pulmonary cystic echinococcosis.

PURPOSE OF REVIEW: The aim of our review is to summarize specific clinical, diagnostic and treatment aspects of pulmonary cystic echinococcosis. The lung is the organ second most affected by cystic echinococcosis with approximately a quarter of cystic echinococcosis cysts. Most cysts are in the liver. Apart from the watch and wait approach for selected inactive cysts [cystic echinococcosis CE4, CE5], the well established WHO cystic echinococcosis cyst classification-based treatment of hepatic cystic echinococcosis cannot be applied to pulmonary cystic echinococcosis cysts. Some standard interventions can even be harmful when applied to pulmonary cystic echinococcosis cysts. RECENT FINDINGS: Cystic echinococcosis is one of the neglected tropical diseases (NTDs). Development of new diagnostics and treatment modalities is hampered by low investment into research and is accordingly slow. SUMMARY: Surgery is the mainstay of treatment for pulmonary cystic echinococcosis cysts. Parenchyma-sparing surgical techniques should be used whenever possible. Albendazole induces decay of the parasitic cyst membrane, opening of cystobronchial fistulas and cyst complications, which can be life threatening. It is strongly recommended to seek advice from expert centres, including differential diagnoses, treatment and a long-term management plan.

Quantification of airway wall contrast enhancement on virtual monoenergetic images from spectral computed tomography.

OBJECTIVES: Quantitative computed tomography (CT) plays an increasingly important role in phenotyping airway diseases. Lung parenchyma and airway inflammation could be quantified by contrast enhancement at CT, but its investigation by multiphasic examinations is limited. We aimed to quantify lung parenchyma and airway wall attenuation in a single contrast-enhanced spectral detector CT acquisition. METHODS: For this cross-sectional retrospective study, 234 lung-healthy patients who underwent spectral CT in four different contrast phases (non-enhanced, pulmonary arterial, systemic arterial, and venous phase) were recruited. Virtual monoenergetic images were reconstructed from 40-160 keV, on which attenuations of segmented lung parenchyma and airway walls combined for 5th-10th subsegmental generations were assessed in Hounsfield Units (HU) by an in-house software. The spectral attenuation curve slope between 40 and 100 keV (λHU) was calculated. RESULTS: Mean lung density was higher at 40 keV compared to that at 100 keV in all groups (p < 0.001). λHU of lung attenuation was significantly higher in the systemic (1.7 HU/keV) and pulmonary arterial phase (1.3 HU/keV) compared to that in the venous phase (0.5 HU/keV) and non-enhanced (0.2 HU/keV) spectral CT (p < 0.001). Wall thickness and wall attenuation were higher at 40 keV compared to those at 100 keV for the pulmonary and systemic arterial phase (p ≤ 0.001). λHU for wall attenuation was significantly higher in the pulmonary arterial (1.8 HU/keV) and systemic arterial (2.0 HU/keV) compared to that in the venous (0.7 HU/keV) and non-enhanced (0.3 HU/keV) phase (p ≤ 0.002). CONCLUSIONS: Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition, and may separate arterial and venous enhancement. Further studies are warranted to analyze spectral CT for inflammatory airway diseases. KEY POINTS: • Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition. • Spectral CT may separate arterial and venous enhancement of lung parenchyma and airway wall. • The contrast enhancement can be quantified by calculating the spectral attenuation curve slope from virtual monoenergetic images.

Hydride formation and dynamic phase changes during template-assisted Pd electrodeposition.

We investigated the structural evolution of electrochemically fabricated Pd nanowiresin situby means of grazing-incidence transmission small- and wide-angle x-ray scattering (GTSAXS and GTWAXS), x-ray fluorescence (XRF) and two-dimensional surface optical reflectance (2D-SOR). This shows how electrodeposition and the hydrogen evolution reaction (HER) compete and interact during Pd electrodepositon. During the bottom-up growth of the nanowires, we show thatß-phase Pd hydride is formed. Suspending the electrodeposition then leads to a phase transition fromß-phase Pd hydride toα-phase Pd. Additionally, we find that grain coalescence later hinders the incorporation of hydrogen in the Pd unit cell. GTSAXS and 2D-SOR provide complementary information on the volume fraction of the pores occupied by Pd, while XRF was used to monitor the amount of Pd electrodeposited.

CT Angiography Clot Burden Score from Data Mining of Structured Reports for Pulmonary Embolism.

Background Many studies emphasize the role of structured reports (SRs) because they are readily accessible for further automated analyses. However, using SR data obtained in clinical routine for research purposes is not yet well represented in literature. Purpose To compare the performance of the Qanadli scoring system with a clot burden score mined from structured pulmonary embolism (PE) reports from CT angiography. Materials and Methods In this retrospective study, a rule-based text mining pipeline was developed to extract descriptors of PE and right heart strain from SR of patients with suspected PE between March 2017 and February 2020. From standardized PE reporting, a pulmonary artery obstruction index (PAOI) clot burden score (PAOICBS) was derived and compared with the Qanadli score (PAOIQ). Scoring time and confidence from two independent readings were compared. Interobserver and interscore agreement was tested by using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. To assess conformity and diagnostic performance of both scores, areas under the receiver operating characteristic curve (AUCs) were calculated to predict right heart strain incidence, as were optimal cutoff values for maximum sensitivity and specificity. Results SR content authored by 67 residents and signed off by 32 consultants from 1248 patients (mean age, 63 years ± 17 [standard deviation]; 639 men) was extracted accurately and allowed for PAOICBS calculation in 304 of 357 (85.2%) PE-positive reports. The PAOICBS strongly correlated with the PAOIQ (r = 0.94; P < .001). Use of PAOICBS yielded overall time savings (1.3 minutes ± 0.5 vs 3.0 minutes ± 1.7), higher confidence levels (4.2 ± 0.6 vs 3.6 ± 1.0), and a higher ICC (ICC, 0.99 vs 0.95), respectively, compared with PAOIQ (each, P < .001). AUCs were similar for PAOICBS (AUC, 0.75; 95% CI: 0.70, 0.81) and PAOIQ (AUC, 0.77; 95% CI: 0.72, 0.83; P = .68), with cutoff values of 27.5% for both scores. Conclusion Data mining of structured reports enabled the development of a CT angiography scoring system that simplified the Qanadli score as a semiquantitative estimate of thrombus burden in patients with pulmonary embolism. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Hunsaker in this issue.

Presentation and outcome of mixed neuroendocrine non-neuroendocrine neoplasms of the pancreas.

BACKGROUND/OBJECTIVES: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) of the pancreas and periampullary region are extremely rare and heterogeneous malignancies. Literature is sparse, clinical management is not standardized and little is known about survival outcomes. The aim of this study was to identify pathological and radiological features of MiNEN and assess the outcome of surgical management. METHODS: Patients undergoing surgery for pancreatic and periampullary MiNEN between 2001 and 2019 were retrospectively analysed based on a prospective database. Histological, radiological and clinical features were assessed. Survival was analysed in a nested case-control study and matched-pair analyses with pure neuroendocrine neoplasms (pNEN) and ductal adeno- or acinar cell carcinomas of the pancreas. A literature review with focus on survival after surgical resection was additionally performed. RESULTS: Of 13 patients with MiNEN, 5 had acinar-MiNEN and 8 adeno-MiNEN. Two of 5 (40%) acinar-MiNEN and one adeno-MiNEN patients had liver metastases. All but one adeno-MiNEN (88%) showed preoperative radiological features of pancreatic adenocarcinoma, 3 of 5 (60%) acinar-MiNEN exhibited mainly neuroendocrine features. No surgical mortality was observed. The 5-year overall survival rate in all MiNEN was 40%. Five-year survival rate was 58% in adeno-MiNEN and comparable to that of matched ductal adenocarcinomas (36%) and pNEN (48%). Five-year overall survival rate was 20% in acinar-MiNEN, compared to 39% in acinar carcinoma patients and 59% in matched pNEN patients. CONCLUSIONS: MiNEN are rare and difficult to distinguish from pure adenocarcinoma or neuroendocrine neoplasm preoperatively. Surgical resection would therefore be the treatment of choice in localized tumors.

Balanced steady-state free precession MRCP is a robust alternative to respiration-navigated 3D turbo-spin-echo MRCP.

BACKGROUND: Despite synchronization to respiration, respiration-navigated (RN) 3D turbo-spin-echo MRCP is limited by susceptibility to motion artifacts. The aim of this study was to assess the quality of pancreaticobiliary duct visualization of a non-RN MRCP alternative based on balanced steady-state free precession imaging (BSSFP) with overlapping slices compared with RN-MRCP. METHODS: This is a retrospective study on 50 patients without pancreaticobiliary duct disease receiving MRCP at 1.5 T. We performed an intraindividual comparison of coronal RN-MRCP with combined coronal and transverse BSSFP-MRCP. Image quality was scored by 3 readers for 6 pancreaticobiliary duct segments (3 pancreatic, 3 biliary) using a 6-point scale. A segment score of 3 or lower as assessed by at least 2 of 3 readers was defined as insufficient segment visualization. Nonparametric tests and interrater reliability testing were used for statistical analysis. RESULTS: Overall duct visualization averaged over all readers was scored with 4.5 ± 1.1 for RN-MRCP (pancreatic, 4.1 ± 0.5; biliary, 5.0 ± 0.4) and 4.9 ± 0.9 for combined coronal and transverse BSSFP-MRCP (pancreatic, 4.6 ± 0.6; biliary, 5.1 ± 0.6), respectively (p < 0.001). The number of segments visualized insufficiently was 81/300 for RN-MRCP and 43/300 for BSSFP-MRCP (p < 0.001). Segments visualized insufficiently only in RN-MRCP had a mean score of 4.4 ± 0.8 in BSSFP-MRCP. Overall interrater agreement on superiority of BSSFP-MRCP segment scores over corresponding RN-MRCP was 0.70. Mean acquisition time was 98% longer for RN-MRCP (198.0 ± 98.7 s) than for combined coronal and transverse BSSFP-MRCP (100.2 ± 0.4 s). CONCLUSIONS: Non-RN BSSFP-MRCP with overlapping slices is a fast alternative to RN-MRCP, frequently providing sufficient duct visualization when RN-MRCP fails.

[Skeletal changes in plasma cell dyscrasias]. / Skelettveränderungen bei Plasmazelldyskrasien.

BACKGROUND: Plasma cell dyscrasias are a spectrum of diseases characterized by clonal plasma cell proliferation. Important entities within this group are monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and symptomatic multiple myeloma. PURPOSE: The goal of this review is to illustrate plasma cell dyscrasia imaging findings of bone and bone marrow as seen on whole-body computed tomography (CT) and magnetic resonance imaging (MRI) and to discuss the relevance of imaging for management of patients with plasma cell dyscrasias. MATERIALS AND METHODS: Selective literature search with analysis of dedicated original research articles and reviews and discussion of clinical guidelines. RESULTS: Diagnostic classification of plasma cell dyscrasias is based on the SLiM-CRAB criteria. CT primarily represents imaging of mineralized bone to show osseous end organ damage by detecting osteodestruction. MRI is primarily used for bone marrow imaging to detect diffuse or focal bone marrow infiltration, even in the absence of bone destruction. Different patterns of bone marrow infiltration can be distinguished. Treatment response is associated with characteristic imaging signs of lesion regression. CONCLUSION: Imaging plays a prominent role in treatment stratification of patients with plasma cell dyscrasia at first diagnosis and during follow-up.

A genome-wide scan study identifies a single nucleotide substitution in MC1R gene associated with white coat colour in fallow deer (Dama dama).

BACKGROUND: The coat colour of fallow deer is highly variable and even white animals can regularly be observed in game farming and in the wild. Affected animals do not show complete albinism but rather some residual pigmentation resembling a very pale beige dilution of coat colour. The eyes and claws of the animals are pigmented. To facilitate the conservation and management of such animals, it would be helpful to know the responsible gene and causative variant. We collected 102 samples from 22 white animals and from 80 animals with wildtype coat colour. The samples came from 12 different wild flocks or game conservations located in different regions of Germany, at the border to Luxembourg and in Poland. The genomes of one white hind and her brown calf were sequenced. RESULTS: Based on a list of colour genes of the International Federation of Pigment Cell Societies ( http://www.ifpcs.org/albinism/ ), a variant in the MC1R gene (NM_174108.2:c.143 T > C) resulting in an amino acid exchange from leucine to proline at position 48 of the MC1R receptor protein (NP_776533.1:p.L48P) was identified as a likely cause of coat colour dilution. A gene test revealed that all animals of the white phenotype were of genotype CC whereas all pigmented animals were of genotype TT or TC. The study showed that 14% of the pigmented (brown or dark pigmented) animals carried the white allele. CONCLUSIONS: A genome-wide scan study led to a molecular test to determine the coat colour of fallow deer. Identification of the MC1R gene provides a deeper insight into the mechanism of dilution. The gene marker is now available for the conservation of white fallow deer in wild and farmed animals.

Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease.

BACKGROUND: Pancreatoblastoma is a rare malignancy that occurs predominantly in children. Less than 50 adult cases, including 17 patients with metastatic disease, have been published to date. Recent outcome data from children with advanced-stage disease suggest an intensive multimodal treatment approach; however, little is known about the most beneficial therapy in adults. Molecular characterization of pancreatoblastoma is limited to a small number of pediatric cases and revealed few recurrent genetic events without immediate clinical relevance. METHODS: Patients were treated between 2013 and 2018 at a high-volume German university cancer center. Molecular analyses included whole genome, exome, transcriptome, and fusion gene panel sequencing. Molecularly guided treatment recommendations were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER). RESULTS: We identified four adult patients with metastatic pancreatoblastoma. In three patients, local approaches were combined with systemic treatment. Oxaliplatin-containing protocols showed an acceptable tumor control as well as an adequate toxicity profile. Overall survival was 15, 17, 18 and 24 months, respectively. Three tumors harbored genetic alterations involving the FGFR pathway that included an oncogenic FGFR2 fusion. CONCLUSION: Oxaliplatin-containing chemotherapy seems to be a reasonable approach in adult patients with advanced pancreatoblastoma, whereas the benefit of intensified treatment including local ablative techniques or surgical resection remains unclear. Our finding of FGFR alterations in three of four cases indicates a potential role of FGFR signaling in adult pancreatoblastoma whose clinical significance warrants further study.

Image quality evaluation of dual-layer spectral CT in comparison to single-layer CT in a reduced-dose setting.

OBJECTIVES: To quantitatively and qualitatively evaluate image quality in dual-layer CT (DLCT) compared to single-layer CT (SLCT) in the thorax, abdomen, and pelvis in a reduced-dose setting. METHODS: Intraindividual, retrospective comparisons were performed in 25 patients who received at least one acquisition of all three acquisition protocols SLCTlow (100 kVp), DLCThigh (120 kVp), and DLCTlow (120 kVp), all covering the venous-phase thorax, abdomen, and pelvis with matched CTDIvol between SLCTlow and DLCTlow. Reconstruction parameters were identical between all scans. Image quality was assessed quantitatively at 10 measurement locations in the thorax, abdomen, and pelvis by two independent observers, and subjectively with an intraindividual forced choice test between the three acquisitions. Dose-length product (DLP) and CTDIvol were extracted for dose comparison. RESULTS: Despite matched CTDIvol in acquisition protocols, CTDIvol and DLP were lower for SLCTlow compared to DLCTlow and DLCThigh (DLP 408.58, 444.68, 647.08 mGy·cm, respectively; p < 0.0004), as automated tube current modulation for DLCTlow reached the lower limit in the thorax (mean 66.1 mAs vs limit 65 mAs). Noise and CNR were comparable between SLCTlow and DLCTlow (p values, 0.29-0.51 and 0.05-0.20), but CT numbers were significantly higher for organs and vessels in the upper abdomen for SLCTlow compared to DLCTlow. DLCThigh had significantly better image quality (Noise and CNR). Subjective image quality was superior for DLCThigh, but no difference was found between SLCTlow and DLCTlow. CONCLUSIONS: DLCTlow showed comparable image quality to SLCTlow, with the additional possibility of spectral post-processing. Further dose reduction seems possible by decreasing the lower limit of the tube current for the thorax. KEY POINTS: • Clinical use of reduced-dose DLCT is feasible despite the required higher tube potential. • DLCT with reduced dose shows comparable objective and subjective image quality to reduced-dose SLCT. • Further dose reduction in the thorax might be possible by adjusting mAs thresholds.

In situ studies of the cathodic stability of single-crystalline IrO2(110) ultrathin films supported on RuO2(110)/Ru(0001) in an acidic environment.

We investigate with in situ surface X-ray diffraction (SXRD) and X-ray reflectivity (XRR) experiments the cathodic stability of an ultrathin single-crystalline IrO2(110) film with a regular array of mesoscopic rooflike structures that is supported on a RuO2(110)/Ru(0001) template. It turns out that the planarity of the single-crystalline IrO2(110) film is lost in that IrO2(110) oxide domains delaminate at a cathodic potential of -0.18 V. Obviously, the electrolyte solution is able to reach the RuO2(110) layer presumably through the surface grain boundaries of the IrO2(110) layer. Subsequently, the single-crystalline RuO2(110) structure-directing template is reduced to amorphous hydrous RuO2, with the consequence that the IrO2(110) film loses partly its adhesion to the template. From in situ XRR experiments we find that the IrO2(110) film does not swell upon cathodic polarization down to -0.18 V, while from in situ SXRD experiments, the lattice constants of IrO2(110) are shown to be not affected. The rooflike mesostructure of the IrO2(110) flakes remains intact after cathodic polarization to -0.18 V, evidencing that the crystallinity of IrO2(110) is retained.

[Diagnostic imaging of malignant lymphomas]. / Bildgebende Diagnostik von malignen Lymphomen.

BACKROUND: Malignant lymphomas represent approximately 5% of all cancers. Imaging procedures play a crucial role concerning initial staging and assessment of the response to treatment. OBJECTIVE: This article gives an overview of the significance of imaging procedures in the treatment of patients with malignant lymphomas at various times during treatment. These include the initial assessment of the extent of the disease and staging during and after treatment under consideration of the current classification systems. MATERIAL AND METHODS: A selective literature search was carried out with analysis of dedicated original research articles and reviews as well as a discussion of the clinical guidelines. RESULTS: Computed tomography (CT) is the basic diagnostic tool in patients with malignant lymphomas. Particularly important is fluorodeoxyglucose (FDG) positron emission tomography (PET) CT, which enables a more accurate stage definition and a better assessment of the response to treatment in FDG-avid lymphoma subtypes. Using the FDG-PET/CT-based Deauville score persisting disease activity can be identified in residual masses and refractory disease can be distinguished from complete metabolic remission. The use of magnetic resonance imaging (MRI) with diffusion-weighted imaging can represent a future alternative but is, however, not yet sufficiently standardized and validated. CONCLUSION: The standardized analysis and reporting of purely morphological and metabolic imaging procedures is the backbone of treatment decisions in patients with malignant lymphomas.

RSPO2 gene rearrangement: a powerful driver of ß-catenin activation in liver tumours.

OBJECTIVE: We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC). DESIGN: Large cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed. RESULTS: A roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of ß-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of ß-catenin and transcriptional activation of ß-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three ß-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter-known to drive malignant transformation of CTNNB1-mutated HCA-seem to be dispensable for RSPO2 rearranged HCA and HCC. CONCLUSION: The RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.

Growth of Ultrathin Single-Crystalline IrO2(110) Films on a TiO2(110) Single Crystal.

The growth of a flat, covering, and single-crystalline IrO2(110) film with controlled film thickness on a single-crystalline TiO2(110) substrate is reported. The preparation starts with a deposition of metallic Ir at room temperature followed by a post-oxidation step performed in an oxygen atmosphere of 10-4 mbar at 700 K. On this surface, additional Ir can be deposited at 700 K in an oxygen atmosphere of 10-6 mbar to produce a IrO2(110) layer with variable thicknesses. To improve the crystallinity of the resulting IrO2(110) layer, the final film was post-oxidized in 10-4 mbar of O2 at 700 K for 5 min. The surface-sensitive techniques of scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and low-energy electron diffraction (LEED) are employed to characterize the morphology, crystallinity, and electronic structure of the prepared ultrathin IrO2(110) films and how these films decompose upon annealing under ultrahigh vacuum (UHV) conditions. STM provides evidence that the IrO2(110) films start already to reduce at 465 K under UHV conditions. Upon annealing to 605 K under UHV the reduction of IrO2 intensifies (XPS), but the oxide film can readily be restored by re-oxidation in 10-4 mbar of O2 at 700 K. Thermal decomposition at 725 K leads, however, to severe reduction of the IrO2(110) layer (XPS, STM) that cannot be restored by a subsequent re-oxidation step. The utility of the IrO2(110)-TiO2(110) system as model electrodes is exemplified with the electrochemical oxygen evolution reaction in an acidic environment.

Is MRCP necessary to diagnose pancreas divisum?

BACKGROUND: The purpose of this study is to compare the performance of three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) with non-MRCP T2-weighted magnetic resonance imaging (MRI) sequences for diagnosis of pancreas divisum (PD). METHODS: This is a retrospective study of 342 consecutive patients with abdominal MRI including 3D-MRCP. 3D-MRCP was a coronal respiration-navigated T2-weighted sequence with 1.5 mm slice thickness. Non-MRCP T2-weighted sequences were (1) a coronal inversion recovery sequence (TIRM) with 6 mm slice thickness and (2) a transverse single shot turbo spin echo sequence (HASTE) with 4 mm slice thickness. For 3D-MRCP, TIRM, and HASTE, presence of PD and assessment of evaluability were determined in a randomized manner. A consensus read by two radiologists using 3D-MRCP, non-MRCP T2-weighted sequences, and other available imaging sequences served as reference standard for diagnosis of PD. Statistical analysis included performance analysis of 3D-MRCP, TIRM, and HASTE and testing for noninferiority of non-MRCP T2-weighted sequences compared with 3D-MRCP. RESULTS: Thirty-three of 342 patients (9.7%) were diagnosed with PD using the reference standard. Sensitivity/specificity of 3D-MRCP for detecting PD were 81.2%/69.7% (p < 0.001). Sensitivity/specificity of TIRM and HASTE were 92.5%/93.9 and 98.1%/97.0%, respectively (p < 0.001 each). Grouped sensitivity/specificity of non-MRCP T2-weighted sequences were 99.8%/91.0%. Non-MRCP T2-weighted sequences were non-inferior to 3D-MRCP alone for diagnosis of PD. 20.2, 7.3%, and 2.3% of 3D-MRCP, TIRM, and HASTE, respectively, were not evaluable due to motion artifacts or insufficient duct depiction. CONCLUSIONS: Non-MRCP T2-weighted MRI sequences offer high performance for diagnosis of PD and are noninferior to 3D-MRCP alone. TRIAL REGISTRATION: Not applicable.

Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial.

BACKGROUND: To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival. RESULTS: Forty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (p = 0.0092). A significant association of ΔSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (p = 0.045). CONCLUSIONS: We demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.

Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies.

BACKGROUND: PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia. PATIENTS AND METHODS: We retrospectively included patients with metastatic cutaneous malignancies treated with pembrolizumab or nivolumab ± ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013 and 09/2016. Arthralgia was characterized by laboratory diagnostics, imaging, and if indicated, rheumatologic consultation. RESULTS: 26 of 195 patients (13.3%) developed arthralgia. The median onset of symptoms was 100 days (7-780 days). Most frequently, arthralgia involved large joints (shoulders, knees) in a predominantly symmetrical pattern. Only two patients were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies. Ten patients developed the clinical picture of arthritis, with seven of them showing synovitis in MRI or PET/CT. Five patients showed inflammation in joints pre-damaged by osteoarthritis. In 11 patients arthralgia could not be specified. The majority of patients was satisfactorily treated with non-steroidal anti-inflammatory drugs (NSAIDs), 23.1% required additional low-dose corticosteroids and only 7.6% of our patients received further immunosuppressive treatment. Patients with arthralgia showed a better treatment response and improved PFS and OS. CONCLUSION: Arthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids.

Clinical management of cystic echinococcosis: state of the art and perspectives.

PURPOSE OF REVIEW: This review draws attention to patients with cystic echinococcosis migrating from highly endemic to non-endemic countries with limited experience in cystic echinococcosis management, to ultrasound-based cyst staging, and to the WHO cyst classification as a powerful, to date underused tool to triage patients into the four currently available treatment modalities. RECENT FINDINGS: In non- and low-prevalence countries, cystic echinococcosis is often misclassified. Differential diagnoses, such as simple cysts and other benign and malignant space-occupying lesions, have similar appearances on imaging. Serology is confirmatory but often disappointing due to sensitivity and specificity problems. There is increasing confidence in assigning uncomplicated cystic echinococcosis cysts to the four treatment modalities [drug treatment (benzimidazoles), percutaneous methods, surgery, watch and wait] on the basis of cyst stage (WHO cyst classification), size and location. However, current best practice is still not widely implemented outside cystic echinococcosis treatment centres, and further consolidation is needed by well-designed clinical trials. Recently published long-term follow-up studies have shown that patients with inactive cyst stages CE4 and CE5 benefit, especially since they do not need any treatment at all if they have not received prior benzimidazole or percutaneous therapy. Instead, cysts that have reached cyst stages CE4 and CE5 through drug treatment do need careful follow-up as they often relapse. Surgical procedures in which the cysts are opened and percutaneous approaches require very careful control of cyst content spillage to the peritoneum, pleura and intravascularly to prevent dissemination - a still too often neglected issue with severe consequences for patients. SUMMARY: Though a neglected disease with predominantly expert-opinion-based treatment strategies, cystic echinococcosis patients can greatly benefit from interdisciplinary management in cystic echinococcosis treatment centres and cyst-stage-based assignment of treatment modalities. Increased suspicion for cystic echinococcosis in migrants from endemic to non-endemic countries is urgently needed at the current level of global mobility.