[Intraductal neoplasms of the pancreas]. / Intraduktale Pankreasneoplasien.

The latest WHO classification of tumors of the digestive system (2019) has introduced new concepts for the stratification of intraductal neoplasms of the pancreas, mostly based on molecular genetics and malignant potential. Among them, pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms (IPMN) are both precursors of pancreatic ductal adenocarcinoma, whereas intraductal oncocytic papillary neoplasms (IOPN) and intraductal tubulopapillary neoplasms (ITPN) are usually associated with less aggressive subtypes of pancreatic cancer and therefore have a much better prognosis. Hence, it is of utmost importance to correctly classify these lesions and to distinguish them from each other as well as from other nonductal types of neoplasms, which can rarely display an intraductal growth, such as neuroendocrine tumors and acinar cell carcinomas. PanIN are microscopic lesions with limited clinical significance. In contrast, all other intraductal neoplasms can be identified as cystic processes and/or solid tumors by means of imaging, thereby setting an indication for a potential surgical resection. This review presents diagnostically relevant aspects of intraductal neoplasms of the pancreas, which are instrumental for the discussion within interdisciplinary tumor boards (resection vs. watch-and-wait strategies) as well as to determine the extent of resection intraoperatively.

[Acute and chronic pancreatitis-summary of the most common types of pancreatitis]. / Akute und chronische Pankreatitis ­ die häufigsten Pankreatitiden im Überblick.

Pancreatitis harbors a spectrum of different inflammatory changes of the pancreas of variable etiology and histopathology. In this context, common variants have to be distinguished from rare variants to optimize therapy. Each type of pancreatitis has characteristic features such as the age of patients and clinical presentation as well as the composition of the inflammatory infiltrates and histological changes.

Deep Learning in Pancreatic Tissue: Identification of Anatomical Structures, Pancreatic Intraepithelial Neoplasia, and Ductal Adenocarcinoma.

Identification of pancreatic ductal adenocarcinoma (PDAC) and precursor lesions in histological tissue slides can be challenging and elaborate, especially due to tumor heterogeneity. Thus, supportive tools for the identification of anatomical and pathological tissue structures are desired. Deep learning methods recently emerged, which classify histological structures into image categories with high accuracy. However, to date, only a limited number of classes and patients have been included in histopathological studies. In this study, scanned histopathological tissue slides from tissue microarrays of PDAC patients (n = 201, image patches n = 81.165) were extracted and assigned to a training, validation, and test set. With these patches, we implemented a convolutional neuronal network, established quality control measures and a method to interpret the model, and implemented a workflow for whole tissue slides. An optimized EfficientNet algorithm achieved high accuracies that allowed automatically localizing and quantifying tissue categories including pancreatic intraepithelial neoplasia and PDAC in whole tissue slides. SmoothGrad heatmaps allowed explaining image classification results. This is the first study that utilizes deep learning for automatic identification of different anatomical tissue structures and diseases on histopathological images of pancreatic tissue specimens. The proposed approach is a valuable tool to support routine diagnostic review and pancreatic cancer research.

Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging.

Purpose: This study aimed to evaluate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) as imaging biomarker for epithelial-to-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC). Methods: In forty-two patients, preoperative apparent diffusion coefficient (ADC) values of therapy-naive PDAC were compared with immunohistochemical expression profiles of the epithelial marker E-cadherin as well as mesenchymal transcription factors Runt-related transcription factor 2 (Runx2) and Zinc finger E-box-binding homeobox 1 (Zeb1), as determined by Allred immunoreactivity score. Results: We observed a significant positive rank correlation between the ADC and the E-cadherin Allred score (ρ = 0.553, p < 0.001) and significant negative rank correlations between the ADC and the Runx2 Allred score (ρ = -0.526, p < 0.001) as well as the Zeb1 Allred score (ρ = -0.710, p < 0.001). Compared to tumors with low ADC values < 1.3 µm2/s, tumors with ADC values ≥ 1.3 µm2/s had significantly higher Allred scores for E-cadherin (median, 4 versus 5; p < 0.001) and significantly lower Allred scores for Runx2 (median, 3 versus 2; p = 0.003) as well as Zeb1 (median, 4 versus 0; p < 0.001). Conclusion: In PDAC, tumor plasticity in terms of EMT is well reflected by ADC values from DW-MRI. In the near future, DW-MRI could be beneficial for identification of PDAC patients that might profit from personalized EMT-targeted therapies.

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia.

Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.

Taming the Cationic Beast: Novel Developments in the Synthesis and Application of Weakly Coordinating Anions.

This Review gives a comprehensive overview of the most topical weakly coordinating anions (WCAs) and contains information on WCA design, stability, and applications. As an update to the 2004 review, developments in common classes of WCA are included. Methods for the incorporation of WCAs into a given system are discussed and advice given on how to best choose a method for the introduction of a particular WCA. A series of starting materials for a large number of WCA precursors and references are tabulated as a useful resource when looking for procedures to prepare WCAs. Furthermore, a collection of scales that allow the performance of a WCA, or its underlying Lewis acid, to be judged is collated with some advice on how to use them. The examples chosen to illustrate WCA developments are taken from a broad selection of topics where WCAs play a role. In addition a section focusing on transition metal and catalysis applications as well as supporting electrolytes is also included.

A systematic investigation of coinage metal carbonyl complexes stabilized by fluorinated alkoxy aluminates.

The reaction of Cu(I), Ag(I), and Au(I) salts with carbon monoxide in the presence of weakly coordinating anions led to known and structurally unknown non-classical coinage metal carbonyl complexes [M(CO)n][A] (A = fluorinated alkoxy aluminates). The coinage metal carbonyl complexes [Cu(CO)n(CH2Cl2)m](+)[A](-) (n = 1, 3; m = 4-n), [Au2(CO)2Cl](+)[A](-), [(OC)nM(A)] (M = Cu: n = 2; Ag: n = 1, 2) as well as [(OC)3Cu⋅⋅⋅ClAl(OR(F))3] and [(OC)Au⋅⋅⋅ClAl(OR(F))3] were analyzed with X-ray diffraction and partially IR and Raman spectroscopy. In addition to these structures, crystallographic and spectroscopic evidence for the existence of the tetracarbonyl complex [Cu(CO)4](+)[Al(OR(F))4](-) (R(F) = C(CF3)3) is presented; its formation was analyzed with the help of theoretical investigations and Born-Fajans-Haber cycles. We discuss the limits of structure determinations by routine X-ray diffraction methods with respect to the C-O bond lengths and apply the experimental CO stretching frequencies for the prediction of bond lengths within the carbonyl ligand based on a correlation with calculated data. Moreover, we provide a simple explanation for the reported, partly confusing and scattered CO stretching frequencies of [Cu(I)(CO)n] units.

Reducing youth access to alcohol: findings from a community-based randomized trial.

Underage drinking continues to be an important public health problem and a challenge to the substance abuse prevention field. Community-based interventions designed to more rigorously control underage access to alcohol through retailer education and greater enforcement of underage drinking laws have been advocated as potentially effective strategies to help address this problem, but studies designed to evaluate such interventions are sparse. To address this issue we conducted a randomized trial involving 36 communities to test the combined effectiveness of five interrelated intervention components designed to reduce underage access to alcohol. The intervention was found to be effective in reducing the likelihood that retail clerks would sell alcohol to underage-looking buyers, but did not reduce underage drinking or the perceived availability of alcohol among high school students. Post hoc analyses, however, revealed significant associations between the level of underage drinking law enforcement in the intervention communities and reductions in both 30-day use of alcohol and binge drinking. The findings highlight the difficulty in reducing youth drinking even when efforts to curtail retail access are successful. Study findings also suggest that high intensity implementation of underage drinking law enforcement can reduce underage drinking. Any such effects of enhanced enforcement on underage drinking appear to be more directly attributable to an increase in perceived likelihood of enforcement and the resultant perceived inconveniences and/or sanctions to potential drinkers, than to a reduction in access to alcohol per se.

Synthesis, characterization, and application of two Al(OR(F))3 Lewis superacids.

We report herein the synthesis and full characterization of the donor-free Lewis superacids Al(OR(F))(3) with OR(F) = OC(CF(3))(3) (1) and OC(C(5)F(10))C(6)F(5) (2), the stabilization of 1 as adducts with the very weak Lewis bases PhF, 1,2-F(2)C(6)H(4), and SO(2), as well as the internal C-F activation pathway of 1 leading to Al(2)(F)(OR(F))(5) (4) and trimeric [FAl(OR(F))(2)](3) (5, OR(F) = OC(CF(3))(3)). Insights have been gained from NMR studies, single-crystal structure determinations, and DFT calculations. The usefulness of these Lewis acids for halide abstractions has been demonstrated by reactions with trityl chloride (NMR; crystal structures). The trityl salts allow the introduction of new, heteroleptic weakly coordinating [Cl-Al(OR(F))(3)](-) anions, for example, by hydride or alkyl abstraction reactions.

Facile access to the pnictocenium ions [Cp*ECl]+ (E = P, As) and [(Cp*)2P]+: chloride ion affinity of Al(OR(F))3.

The pnictocenium salts [Cp*PCl]+ [µCl]− (1 a), [Cp*PCl]+ [ClAl(OR(F))3]− (1 b), [Cp*AsCl]+ [ClAl(OR(F))3]− (2), and [(Cp*)2P]+ [µCl]− (3), in which Cp* = Me5C5, µCl = ((F)RO)3Al-Cl-Al(OR(F))3, and OR(F) = OC(CF3)3, were prepared by halide abstraction from the respective halopnictines with the Lewis superacid PhF→Al(OR(F))3. The X-ray crystal structures of 1 a, 2, and 3 established that in the half as well as in the sandwich cations the Cp* rings are attached in an η2-fashion. By using one or two equivalents of the Lewis acid, the two new weakly coordinating anions [µCl]− and [ClAl(OR(F))3]− resulted. They also stabilize the highly reactive cations in PhF or 1,2-F2C6H4 solution at room temperature. The chloride ion affinities (CIAs) of a range of classical strong Lewis acids were also investigated. The calculations are based on a set of isodesmic BP86/SV(P) reactions and a non-isodesmic reference reaction assessed at the G3MP2 level.

Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies.

BACKGROUND: Limited health care budgets have raised the issue of how much therapy should be dedicated to critically ill patients with multiorgan and acute renal failure (ARF). No data are available on patients with ARF after hospital discharge. METHODS: We assessed long-term survival and quality of life after discharge. Nine hundred seventy-nine patients with ARF who needed continuous renal replacement therapies were analyzed retrospectively. Contact was achieved by questionnaires assessing health status and mental and physical well-being. RESULTS: The in-hospital mortality rate was 69% (n = 678). Postdischarge information was obtained from 89% (n = 267). Kaplan-Meier analyses showed surprisingly good postdischarge survival. Discharged patients had a 77% probability to survive the first 6 months. Those who did so had a probability of 89% to survive the following 6 months. After 5 years, the survival probability was 50%. Age and more than one comorbidity before hospitalization were associated with significantly lower postdischarge survival. Seventy-seven percent of questionnaire responders assessed their current health status as good to excellent, 57% were self-sustaining, and 49% stated that their quality of life had improved. Renal insufficiency remained in 41%, whereas 10% required chronic dialysis therapy. CONCLUSION: ARF is associated with a high in-hospital mortality rate. Nevertheless, patients leaving the hospital had a reasonable survival rate and good quality of life. We conclude that aggressive intensive care unit treatment is justified in these patients.