[Duodenal bleeding due to metastasis from lung adenocarcinoma controlled by radiotherapy: A case report and literature review]. / Saignement duodénal dû à une métastase d'un cancer pulmonaire contrôlé par radiothérapie : cas clinique et revue de la littérature.

INTRODUCTION: Gastrointestinal (GI) metastases in lung cancer rarely occur. CASE REPORT: We report here the case of a 43-year-old male active smoker who was admitted to our hospital for cough, abdominal pain and melena. Initial investigations revealed poorly differentiated adenocarcinoma of the superior-right lobe of the lung: positive for thyroid transcription factor-1 and negative for protein p40 and for antigen CD56, with peritoneal, adrenal and cerebral metastasis, as well as anemia requiring major transfusion support. Over 50% of cells were positive for PDL-1, and ALK gene rearrangement was detected. GI endoscopy showed a large ulcerated nodular lesion of the genu superius with active intermittent bleeding, as well as an undifferentiated carcinoma with positivity for CK AE1/AE3 and TTF-1, and negativity for CD117, corresponding to metastatic invasion originating from lung carcinoma. Palliative immunotherapy with pembrolizumab was proposed, followed by targeted therapy with brigatinib. Gastrointestinal bleeding was controlled with a single 8Gy dose of haemostatic radiotherapy. CONCLUSION: GI metastases are rare in lung cancer and present nonspecific symptoms and signs but no characteristic endoscopic features. GI bleeding is a common revelatory complication. Pathological and immunohistological findings are critical to diagnosis. Local treatment is usually guided by the occurrence of complications. In addition to surgery and systemic therapies, palliative radiotherapy may contribute to bleeding control. However, it must be used cautiously, given a present-day lack of evidence and the pronounced radiosensitivity of certain gastrointestinal tract segments.

Challenges for cocaine detection in smuggling samples.

Screening of seized cocaine powders is routinely performed by means of colour tests. An alternative fast screening technique is Mid-InfraRed (MIR) spectroscopy. In the context of smuggling cases, however, drugs are often processed to circumvent detection. In this study, the current screening techniques (cocaine colour test and MIR spectroscopy using libraries and chemometrics) were applied to five smuggling cases. For each case, all samples were first screened with a cocaine colour test and MIR analysis, followed by confirmation analyses with GC-MS and GC-FID to identify and quantify cocaine and cutting agents. Finally, Scanning Electron Microscopy-Energy Dispersive X-ray spectroscopy (SEM-EDX) analyses were performed for additional characterization. All smuggling samples tested negative, both on-site as in the laboratory, for cocaine with the cocaine colour test. Four smuggling cases consisted of coloured samples. Consequently the colour test result was influenced because discolouration of the test showed almost the same colour as the colour of the powders (brown, green, red or black). In contrast, the (coloured) powders could be measured with MIR, but the MIR spectra showed no hit for cocaine using a reference library search. Moreover, cocaine was not detected in four out of the five cases after application of a chemometric classification model. GC-MS analysis, the golden standard for identification, resulted in a positive identification of cocaine in all cases. These samples contained cocaine ranging between 0.8w% and 35w%. Taking into account the results of the screening, the chromatographic and the SEM-EDX analyses, it could be presumed that cocaine was masked. False negative screening results were caused by chemically modified cocaine and/or cocaine mixed with coloured powders. In additional experiments, a sample extraction step prior to the screening techniques was performed. Two sample preparation methods (acetone and ethyl acetate) were tested and resulted in a positive screening of cocaine with the colour test and/or MIR spectroscopy. It can be concluded that the outcome of screening techniques such as colour tests and MIR spectroscopy is only presumptive and should always be confirmed.

Evaluation of a calibration transfer between a bench top and portable Mid-InfraRed spectrometer for cocaine classification and quantification.

A portable Fourier Transform Mid-InfraRed (FT-MIR) spectrometer using Attenuated Total Reflectance (ATR) sampling is used for daily routine screening of seized powders. Earlier, ATR-FT-MIR combined with Support Vector Machines (SVM) algorithms resulted in a significant improvement of the screening method to a reliable and straightforward classification and quantification tool for both cocaine and levamisole. However, can this tool be transferred to new (hand-held) devices, without loss of the extensive data set? The objective of this study was to perform a calibration transfer between a newly purchased bench top (BT) spectrometer and a portable (P) spectrometer with existing calibration models. Both instruments are from the same brand and have identical characteristics and acquisition parameters (FT instrument, resolution of 4 cm-1 and wavenumber range 4000 to 500 cm-1). The original SVM classification model (n = 515) and SVM quantification model (n = 378) were considered for the transfer trial. Three calibration transfer strategies were assessed: 1) adjustment of slope and bias; 2) correction of spectra from the new instrument BT to P using Piecewise Direct Standardization (PDS) and 3) building a new mixed instrument model with spectra of both instruments. For each approach, additional cocaine powders were measured (n = 682) and the results were compared with GC-MS and GC-FID. The development of a mixed instrument model was the most successful in terms of performance. The future strategy of a mixed model allows applying the models, developed in the laboratory, to portable instruments that are used on-site, and vice versa. The approach offers opportunities to exchange data within a network of forensic laboratories using other FT-MIR spectrometers.

Practical tool for sampling and fast analysis of large cocaine seizures.

Large quantities of illicit drugs are frequently seized by law enforcement. In such cases, a representative number of samples needs to be quickly examined prior to destruction. No procedure has yet been set up which rapidly provides information regarding the homogeneity of the samples, the presence of controlled substances, and the degree of purity. This study establishes a protocol for fast analysis of cocaine and its most common cutting agent, levamisole, in large seizures. The protocol is based on a hypergeometric sampling approach combined with Fourier-transform infrared (FTIR) spectrometry and support vector machines (SVM) algorithms as analysis methods. To demonstrate the practical use of this approach, 5 large cocaine seizures (consisting between 45 and 85 units) were analysed simultaneously with gas chromatography-mass spectrometry (GC-MS), gas chromatography-flame ionisation detector (GC-FID), and a portable FTIR spectrometer using attenuated total reflectance (ATR) sampling combined with SVM models. According to the hypergeometric sampling plan of the guidelines of the Drugs Working Group (DWG) of the European Network of Forensic Science Institutes (ENFSI), the required number of subsamples ranged between 19 and 23. Considering the identification analyses, the SVM models detected cocaine and levamisole in all subsamples of Cases 1 to 5 (100% correct classification), which was confirmed by GC-MS analysis. Considering the quantification analyses, the SVM models were able to estimate the cocaine and levamisole content in each subsample, compared to GC-FID data. The developed strategy is easy, cost effective, and provides immediate information about both the presence and concentration of cocaine and levamisole. By using this new strategy, the number of confirmation analyses with laborious and expensive chromatographic techniques could be significantly reduced.

From uremic toxin retention to removal by convection: do we know enough?

The uremic syndrome is defined by a complex clinical picture, characterized by the dysfunction of most organs which are affected by the retention of multiple solutes. Recent research has helped to unravel the pathophysiology and to identify several as yet unknown responsible compounds. In this publication, we summarize which compounds play the most important pathophysiologic role, and which dialysis strategies can be considered to decrease their concentration and improve outcomes. The main pathophysiologic role is played by molecules which are so-called 'difficult to remove by dialysis'. Essentially observational studies have suggested that enhancement of removal of these molecules, by improving convection (hemodiafiltration), creates an improvement of survival. The knowledge of uremic toxicity is still far from complete however, and we need extra information about responsible compounds and mechanisms, eventually leading to a classification of the most important culprits, to allow the development of even more efficient or specific removal strategies.

Uremic toxins: do we know enough to explain uremia?

BACKGROUND: The uremic syndrome is characterized by a complex clinical picture, whereby the function of multiple organ systems is affected by the retention of a host of solutes. Recent research of the last decade has helped to unravel multiple pathophysiologic mechanisms and to identify as yet unknown responsible compounds. METHODS: The literature was screened to appreciate which compounds play the most important pathophysiologic role. RESULTS: The picture that ensues is that the main role is played by molecules which are so-called 'difficult to remove by dialysis'. The knowledge of uremic toxicity is still far from complete and we need extra information about responsible compounds and mechanisms, eventually leading to a classification of the most important culprits, to allow the development of efficient removal strategies and of pharmacologic methods to counteract pathophysiologic mechanisms. CONCLUSIONS: Uremic retention is a complex phenomenon and the most toxic compounds are difficult to remove by dialysis. Furthermore, our knowledge of the responsible pathways is still incomplete, and needs to be extended to develop new and more efficient treatment strategies.

What is uremia? Retention versus oxidation.

The uremic syndrome is characterized by the retention of a host of compounds which in healthy subjects are secreted into the urine by the healthy kidneys. These compounds disturb many physiologic functions, resulting in toxicity. However, many of the retained compounds as well as many of the pathophysiologic actions of the known retention solutes remain unknown. In this publication, we review recent information on uremic toxicity. Especially the difficulty to remove compounds, such as protein-bound compounds and larger molecules, seems to play a crucial role. New strategies enhancing their removal might be highly useful. Part of the retained compounds are the result of oxidative processes due to the inflammatory status of uremic patients; however, other compounds are not, and even the concentration of oxidative compounds will be further increased by disturbances of urinary clearance.