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A 76-year-old man was diagnosed with a hematological neoplasm combining myelodysplastic and myeloproliferative characteristics back in July 2021. Five months after the diagnosis, his condition got more severe when the blasts rose up to 14%, so he was started on hypomethylating agent-based therapy. A few weeks later, the patient was hospitalized after developing fever and a pain in the right thigh. To exclude any source of occult infection, an 18 F-FDG PET/CT was performed. FDG PET/CT showed a complete lack of metabolism in the right femur. An MRI and a biopsy confirmed the suspected diagnosis of osteonecrosis.

Metastatic bone disease (MBD) is the most common form of metastases, most frequently deriving from prostate cancer. MBD is screened with bone scintigraphy (BS), which have high sensitivity but low specificity for the diagnosis of MBD, often requiring further investigations. Deep learning (DL) - a machine learning technique designed to mimic human neuronal interactions- has shown promise in the field of medical imaging analysis for different purposes, including segmentation and classification of lesions. In this study, we aim to develop a DL algorithm that can classify areas of increased uptake on bone scintigraphy scans. We collected 2365 BS from three European medical centres. The model was trained and validated on 1203 and 164 BS scans respectively. Furthermore we evaluated its performance on an external testing set composed of 998 BS scans. We further aimed to enhance the explainability of our developed algorithm, using activation maps. We compared the performance of our algorithm to that of 6 nuclear medicine physicians. The developed DL based algorithm is able to detect MBD on BSs, with high specificity and sensitivity (0.80 and 0.82 respectively on the external test set), in a shorter time compared to the nuclear medicine physicians (2.5 min for AI and 30 min for nuclear medicine physicians to classify 134 BSs). Further prospective validation is required before the algorithm can be used in the clinic.

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA -rearranged lung adenocarcinoma who developed a A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.

La DM est une maladie inflammatoire auto-immune touchant la peau et les muscles, dont l’étiologie reste souvent inconnue. Les DM induites par des agents biologiques comme les inhibiteurs du tumor necrosis factor alpha sont rares, décrites principalement chez des patients souffrant d’affections auto-immunes ou de néoplasies sous-jacentes. Nous rapportons le cas d’une patiente âgée de 57 ans, développant une DM à anticorps anti-SAE 1/2 suite à un traitement par adalimumab instauré dans le cadre d’une maladie de Verneuil réfractaire. Notre patiente présentait des lésions cutanées typiques (rash héliotrope, papules de Gottron), des arthralgies, des gonflements articulaires, une faiblesse musculaire proximale et une dysphagie. La biologie montrait un faible syndrome inflammatoire, une hypergammaglobulinémie polyclonale, une hypoalbuminémie, des LDH élevés, des CK, GOT et GPT normales. Les anticorps spécifiques des myosites reviennent positifs pour les anticorps anti-SAE 1/2. L’EMG et la biopsie musculaire montrent une myopathie inflammatoire. Une corticothérapie systémique a été démarrée, avec une amélioration des douleurs articulaires et de la force musculaire après 7 jours. Une récidive clinique de la pathologie survient lors de la dégression de la corticothérapie, nécessitant l’instauration d'un traitement par azathioprine avec une bonne réponse clinique et biologique., [Anti-SAE ½ antibody-associated dermatomyositis on adalimumab treatment: a case report] Dermatomyositis (DM) is an autoimmune inflammatory disorder affecting the skin and muscles, whose etiology is often unknown. While DM induced by biological agents like anti-tumor necrosis factor-alpha agents is uncommon, this disorder is mainly seen in patients with autoimmune disorders or underlying neoplasms. We report the case of a 57-year-old female patient who developed DM with anti-small ubiquitin-like modifier-1 activating enzyme (anti-SAE 1/2) antibodies following an adalimumab treatment on account of refractory hidradenitis suppurativa. Our patient presented typical cutaneous findings consisting of heliotrope rash, Gottron papule, arthralgia, joint swelling, proximal muscle weakness, and dysphagia. Laboratory studies showed mild inflammatory syndrome, polyclonal hypergammaglobulinemia, hypoalbuminemia, high LDH levels, yet normal CK, AST, and ALT levels. Myositis-specific antibody assay was found to be positive for anti-SAE 1/2 antibodies. The electromyogram (EMG) and muscle biopsy revealed inflammatory myopathy. Systemic corticosteroid therapy was initiated. As a result, the patient’s joint pain and muscle strength both improved following 7 days of treatment. A clinical recurrence of the pathology occurred during the gradual regression of corticosteroid therapy, requiring the initiation of azathioprine with both good clinical and biological responses.

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Myelolipoma is a rare mesenchymal tumor consisting of adipose tissue and hematopoietic cells. Found usually in the adrenal region, however, few cases have been reported in extra-adrenal regions, most frequently in the presacral region. It is important to recognize such tumor, as it can attain massive size and causes pressure symptoms, and needs to be differentiated from malignant tumors, including liposarcomas. Although CT and MRI can suggest a diagnosis of myelolipoma, these are not conclusive. The hematopoietic cells are enhanced by a Tc-albumin nanocolloid scintigraphy and help to distinguish myolipoma from other entities.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disorder. Liver cysts are the most common extrarenal manifestation of the disease and usually remain asymptomatic. Liver cyst infection is rare, and its treatment is challenging. Liver transplantation (LT) is the only curative therapeutic option in symptomatic polycystic liver disease associated with ADPKD. Only a few cases of LT for recurrent liver cyst infection have been published. To our knowledge, we report the first case of sequential liver-kidney transplantation for recurrent liver cysts infection in a patient with ADPKD. A 55-year-old woman with ADPKD who had a kidney transplantation (KT) presented with multiple liver cysts infection 9 months after her KT. These episodes started after biliary tract complications due to an ampullary adenoma necessitating multiple endoscopic interventions. Her general status gradually degraded because antibiotic treatment was not effective, and she underwent LT for recurrent liver cysts infection 1 year and 9 months after her KT. LT in this setting turned out to be challenging but was possible. We think that better biliary tract workup before KT may prompt better care in these patients.

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines.

BACKGROUND: Serious adverse drug reactions have been associated with the underuse or the misuse of oral anticoagulant therapy. We systematically reviewed the impact of computerized clinical decision support systems (CDSS) on the prescribing of oral anticoagulants and we described CDSS features associated with success or failure. METHODS: We searched Medline, Embase, CENTRAL, CINHAL, and PsycINFO for studies that compared CDSS for the initiation or monitoring of oral anticoagulants with routine care. Two reviewers performed study selection, data collection, and risk-of-bias assessment. Disagreements were resolved with a third reviewer. Potentially important CDSS features, identified from previous literature, were evaluated. RESULTS: Sixteen studies were included in our qualitative synthesis. Most trials were performed in primary care (n = 7) or hospitals (n = 6) and included atrial fibrillation (AF) patients (n = 9). Recommendations mainly focused on anticoagulation underuse (n = 11) and warfarin-drug interactions (n = 5). Most CDSS were integrated in electronic records or prescribing and provided support automatically at the time and location of decision-making. Significant improvements in practitioner performance were found in 9 out of 16 studies, while clinical outcomes were poorly reported. CDSS features seemed slightly more common in studies that demonstrated improvement. CONCLUSIONS: CDSS might positively impact the use of oral anticoagulants in AF patients at high risk of stroke. The scope of CDSS should now evolve to assist prescribers in selecting the most appropriate and tailored medication. Efforts should nevertheless be made to improve the relevance of notifications and to address implementation outcomes.

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

BACKGROUND : Potential inappropriate use of direct oral anticoagulants (DOACs) increases the risk of thromboembolic and haemorrhagic events. PURPOSE : To determine the net cost benefit of clinical pharmacy interventions on the prescription of DOACs. METHOD : We constructed a decision tree model using a public payer perspective. The appropriateness of the prescription was assessed using the Medication Appropriateness Index. The theoretical risks were collected from the literature and the individual potential risks were calculated using the Nesbit risk assignment conducted by two independent clinical pharmacists. Different costs were included based on diagnosis-related group coding and data in the literature. A univariate sensitivity analysis was performed. RESULTS : Thirty-six of 75 patients had an inappropriate prescription of DOACs. The saved difference between avoided costs (7954€) and annualised medication costs and pharmacist cost (4323€) was 3631€ for 75 patients. CONCLUSIONS : In addition to the enhancement of the quality of the prescription, our results indicate that pharmacist interventions provide a positive net cost benefit.

The incidence of thyroid cancer has increased markedly in recent decades, but has been stable in terms of mortality rates. For the most part, these cancers are treated with surgery, which may or may not be followed by radioactive iodine depending on the tumor subtype. Still, many of these cancers will recur and may be treated with radioactive iodine or another surgery. It is unclear what treatment is best for cases of locally advanced or metastatic thyroid cancer that are refractory to radioactive iodine. Chemotherapy has a very low response rate. However, in the past few years, several systemic therapies, primarily targeted, have emerged to improve the overall survival of these patients. Alternative treatments are also of interest, namely peptide receptor radionuclide therapy or immunotherapy.

We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin's lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after two cycles of doxorubicine, bleomycin, vinblastine, dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. IPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale. The prognostic value of TMTV was evaluated and compared to baseline characteristics, staging classifications and iPET2. A total of 258 patients were eligible, 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 PFS and 12 OS events. TMTV was prognosticator of PFS (p<0.0001) and OS (p=0.0001) with an 86% and 84% specificity respectively. The 5y-PFS and OS were 71% and 83% in the high TMTV (>147cm) group (n=46) vs. 92% and 98% in the low TMTV group (≤147cm). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared to the current staging systems proposed by EORTC/GELA, GHSG, or NCCN groups. TMTV and iPET2 were independently prognostic and combined identified four risk groups: low (TMTV≤147+DS1-3; 5y-PFS 95%), low-intermediate (TMTV>147+DS1-3; 5y-PFS 81.6%), high-intermediate (TMTV≤147+DS4-5; 5y-PFS 50%) and high (TMTV>147+DS4-5; 5y-PFS 25%). TMTV improves baseline risk stratification of early stage HL patients compared to current staging systems and the predictive value of early PET response as well.

It is now well demonstrated that (F)-fluorodeoxyglucose PET/CT is the most accurate imaging method for determining disease extent in Hodgkin lymphoma. Thus, up-front PET/CT is mandatory for involved node radiation therapy design. For a proper use of this new imaging modality for radiotherapy, some adaptations should be made to the PET/CT acquisition as well as to the report. Initial PET/CT should be performed in the radiotherapy treatment position. Nuclear medicine physicians should report to the radiation oncologist the precise location of each involved lymph node, for which the use of a common atlas of upper diaphragmatic nodal stations could be useful. All these new procedures have to be implemented in close collaboration among the different medical specialists providing care to Hodgkin lymphoma patients. We report here the usual procedures of PET/CT acquisition in the radiotherapy environment and propose a more sophisticated description of the different lymph nodes for a more efficient nuclear medicine report to the radiation oncologist., [Imagerie multimodale incluant la TEP/TDM au (18F)-fluorodésoxyglucose pour ladélinéation des champs d’irradiation du lymphome de Hodgkin localisé] Il est maintenant clairement établi que la TEP/tomodensitométrie au (18F)-fluorodésoxyglucose est la technique d’imagerie de référence pour le bilan d’extension des lymphomes de Hodgkin. Par conséquent, l’utilisation de la TEP/tomodensitométrie est indispensable pour la réalisation d’une radiothérapie de type involved-node. L’utilisation de cette imagerie fonctionnelle par les radiothérapeutes nécessite une acquisition des images et un compte rendu d’examen particuliers. La TEP préthérapeutique doit être réalisée en position de traitement. Le compte rendu doit décrire précisément l’ensemble des ganglions supposés envahis, raison pour laquelle une classification unique décrivant l’ensemble des aires ganglionnaires sus-diaphragmatiques est proposée. Cette nouvelle technique thérapeutique nécessite une collaboration étroite entre différentes spécialités médicales. Cet article a pour objet la description de la réalisation pratique de la TEP/tomodensitométrie en position de radiothérapie ainsi qu’une trame de compte rendu d’examen prenant en compte la description des différents ganglions sus-diaphragmatiques.

Fluorodeoxyglucose (FDG) positons emission tomography (PET)-computed tomography (CT) is used in many ways at baseline and during the treatment of patients with Hodgkin lymphoma. Many properties of the technique are used in the different steps of patient's management. Initial staging with PET-CT is more accurate than conventional imaging and PET-CT also became the gold standard imaging at the end of treatment with a negative PET-CT mandatory for reaching a complete remission. Early assessment of response by PET-CT is one of the most powerful prognostic factors for progression-free survival of patients with localized and advanced stages and allows guiding treatment. Conversely, previous studies showed that there is no role of FDG PET-CT for the patient's follow-up., [Place de la TEP-tomodensitométrie au fluorodésoxyglucose dans la prise en charge thérapeutique du lymphome de Hodgkin] La tomographie par émission de positrons (TEP)-tomodensitométrie au fluorodésoxyglucose est utilisée de différentes manières au moment du diagnostic et pendant le traitement des lymphomes de Hodgkin. Plusieurs particularités de la TEP sont utilisées à différentes étapes de la prise en charge des patients. Lors du bilan initial, la TEP-tomodensitométrie est plus performante que les techniques d’imageries conventionnelles, mais l’est aussi en fin de traitement, un examen normal étant indispensable pour affirmer l’obtention d’une rémission complète. L’évaluation précoce en cours de traitement est un des facteurs pronostiques les plus puissants pour la survie sans progression et pour guider le traitement dans les maladies localisées et disséminées. À l’inverse, la TEP-tomodensitométrie n’a pas de rôle dans le suivi des patients.

L’évaluation du fonctionnement cérébral par l’imagerie moléculaire, tant la tomographie à émission de positrons (PET) que la tomographie par émission monophotonique (SPECT),contribuent de plus en plus au diagnostic positif des maladies neurodégénératives, principalement des démences et des syndromes parkinsoniens. En l’absence actuelle de traitement modifiant l’évolution de la maladie, la plupart des patients sont souvent diagnostiqués cliniquement, sans recourir à l’imagerie moléculaire. Ceci explique que leur prescription, hormis l’étude de la perfusion cérébrale au SPECT, soit réservée aux médecins spécialistes: neurologues, neuropsychiatres ou gériatres. Les examens d’imagerie moléculaire possèdent une importante valeur prédictive,tant positive que négative, qui les aide dans les cas difficiles.

Background Initiatives are needed to promote and evaluate clinical pharmacy. In this context, benchmarking could be useful. Objective To develop and validate a benchmarking tool for clinical pharmacy activities. Setting Six Belgian hospitals. Method A narrative literature review and two focus groups were performed to identify (1) clinical pharmacy benchmarking projects, (2) clinical pharmacy activities with a proven positive impact on the quality of care for patients, (3) quality indicators and (4) contextual factors to be included in the tool. Next, a Delphi survey and a test of the tool in practice led to content validation and usability of the benchmarking tool. Main Outcome Measure To identify quality indicators and contextual factors to be included in the tool. Results Three Delphi rounds were required (rounds 1-2: 9 participants, round 3: 8 participants). Ten quality indicators and 36 relevant contextual factors were selected. These 10 quality indicators represent 6 clinical pharmacy activities that demonstrated to improve patient outcomes: medication reconciliation at admission, patient monitoring, information provided to the health care team, patient education, discharge and transfer medication counselling, and adverse drug reaction monitoring. To collect the information needed to compose the quality indicators and to benchmark, the tool consists of three data collection instruments. An instruction manual accompanies the tool. Conclusion We have developed and validated a benchmarking tool, designed to identify and promote clinical pharmacy activities that demonstrated to improve patient outcomes. Future perspectives include the use of the tool on a national scale to identify the most efficient practices and their enablers and barriers.

Le myélome multiple (MM) est le 2e cancer hématologique en termes de fréquence, avec plus de 700 nouveaux cas chaque année en Belgique. Des données de plus en plus nombreuses suggèrent que la tomographie par émission de positons couplée à la tomodensitométrie au fluorodésoxyglucose marqué au fluor-18 (PET/CT au FDG) a un rôle important à jouer, non seulement au moment du diagnostic du myélome, mais également dans le suivi. Dans le bilan initial d’un MM symptomatique, il permettrait de visualiser entre 40 et 60% de nouvelles lésions, même si le bilan radiologique squelettique est négatif. Le PET/CT au FDG a une sensibilité comparable à l’IRM conventionnelle, mais ne détecte pas nécessairement les mêmes localisations. Pour le pronostic initial, le PET/CT au FDG semble plus performant que l’IRM classique. La mise en évidence de plus de 3 lésions focales ou la présence de lésions extra-médullaires hypermétaboliques est associée à un taux de survie moindre ou à une survie sans progression diminuée. Dans le cadre du suivi, il permet de prédire certaines populations à risque de progression vers un MM, de surveiller des MM non sécrétants et de distinguer les lésions actives des lésions séquellaires. Pour faciliter l’utilisation clinique du PET/CT au FDG dans le MM, un travail de standardisation de son interprétation est cependant nécessaire.

OBJECTIVES: Medication reconciliation (MedRec) is essential for reducing patient harm caused by medication discrepancies across care transitions. Electronic support has been described as a promising approach to moving MedRec forward. We systematically reviewed the evidence about electronic tools that support MedRec, by (a) identifying tools; (b) summarizing their characteristics with regard to context, tool, implementation, and evaluation; and (c) summarizing key messages for successful development and implementation. MATERIALS AND METHODS: We searched PubMed, the Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, and the Cochrane Library, and identified additional reports from reference lists, reviews, and patent databases. Reports were included if the electronic tool supported medication history taking and the identification and resolution of medication discrepancies. Two researchers independently selected studies, evaluated the quality of reporting, and extracted data. RESULTS: Eighteen reports relative to 11 tools were included. There were eight quality improvement projects, five observational effectiveness studies, three randomized controlled trials (RCTs) or RCT protocols (ie, descriptions of RCTs in progress), and two patents. All tools were developed in academic environments in North America. Most used electronic data from multiple sources and partially implemented functionalities considered to be important. Relevant information on functionalities and implementation features was frequently missing. Evaluations mainly focused on usability, adherence, and user satisfaction. One RCT evaluated the effect on potential adverse drug events. CONCLUSION: Successful implementation of electronic tools to support MedRec requires favorable context, properly designed tools, and attention to implementation features. Future research is needed to evaluate the effect of these tools on the quality and safety of healthcare.

BACKGROUND: [123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation. RESULTS: BRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction. Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the "true" values (p < 0.001). Calibration provided, in fact, "first order" camera-dependent corrections, but could not include "second order" subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), w

Two hundred and ten nuclear medicine physicians, radiologists, and hematologists from 26 countries attended the 6th International Workshop on Positron Emission Tomography (PET) in Lymphoma and Myeloma held in Menton, France, in September 2016. The meeting was under the auspices of the European Lymphoma Institute (ELI), the European Association of Nuclear Medicine (EANM) the Lymphoma Study Association (LYSA), the Italian Foundation on Lymphoma (FIL) and the Carnot Institute for Lymphoma (CALYM). Forty scientific posters were presented. For the first time, specialists in the field of multiple myeloma (MM) were involved in the expert session. The aim was to establish from the experience of Italian and French studies new guidelines of FDG-PET/CT reporting for myeloma staging and restaging. The meeting dedicated an entire session to MM imaging followed by a session on the role of PET in Peripheral T cell Lymphoma. An entire session addressed the issues of Deauville scale particularly for end treatment assessment and the challenging consequences of immunomodulatory treatments on PET reporting. A specific session presented the potential role of baseline metabolic tumor measurement to predict outcome and identify different risk categories and the main results obtained in different lymphoma entities were described. Whether it could replace clinical staging has been extensively discussed. The more recent results obtained in the H10 trial have been presented and compared to the published data in early stage Hodgkin lymphoma. Finally, the ongoing studies using PET for guiding therapeutic strategies have been reported by the various lymphoma cooperative groups that participated to the meeting.

BACKGROUND: The survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism. MATERIAL AND METHODS: We have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible. RESULTS: Some drugs appear to be feasible options for patients with hepatic insufficiency. Agents such as 5-fluorouracil and oxaliplatin, as well as monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab, can potentially be used in these cases. On the other hand, irinotecan and regorafenib cannot be recommended because of the risk of increased toxicity. CONCLUSION: Treatment of patients with colorectal cancer and liver dysfunction represents a major challenge because the prognosis is usually very poor and alteration of liver function is normally an exclusion criterion in clinical trials. In this review, we present evidence regarding the use of each drug in patients with colorectal cancer and hepatic impairment.

INTRODUCTION: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. METHODS: Anti-CD105 mAbs were radioiodinated directly using chloramine-T ((125)I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker ((125)I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. RESULTS: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24h for (125)I-anti-CD105-mAbs (91.9±4.0%ID/ml) versus(125)I-KRYRR-anti-CD105-mAbs (4.4±0.6%ID/ml). Tumor uptake of (125)I-anti-CD105-mAbs (0.9±0.3%ID/ml) was significantly lower than that of (125)I-KRYRR-anti-CD105-mAbs (4.7±0.2%ID/ml). CONCLUSIONS: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.

PURPOSE: Quantitative estimates of dopamine transporter availability, determined with [(123)I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [(123)I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. METHODS: Of 73 healthy subjects from the European Normal Control Database of [(123)I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific "to kBq/ml" calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [(123)I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. RESULTS: The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. CONCLUSION: QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [(123)I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding.

PURPOSE: Even though [(123)I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). METHODS: We identified 101 patients with inconclusive findings who underwent an [(123)I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. RESULTS: Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. CONCLUSION: The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [(123)I]FP-CIT SPE

Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

Aims: Antibody-labelled gold nanoparticles represent an attractive tool for cancer imaging and therapy. In this study, the anti-CD105 antibody was conjugated with gold nanoparticles (AuNPs) for the first time. The antibody biodistribution in mice before and after conjugation to AuNPs was studied, with a focus on tumor targeting. Materials & methods: Antibodies were radiolabelled with (89)Zr before conjugation to AuNPs (5 nm). Immunonanoconjugates were characterized in vitro in terms of size, stability in plasma and binding to the target. Quantitative PET imaging and ICP-MS analysis assessed in vivo distribution and specific tumor targeting of tracers. Results: The tumor uptake of immunoconjugates was preserved up to 24 h after injection, with high tumor contrast and selective tumor targeting. No major tracer accumulation was observed over time in nonspecific organs. ICP-MS analysis confirmed the antibody specificity after nanoparticle conjugation. Conclusion: The anti-CD105 antibody conjugation to AuNPs did not greatly affect CD105-dependent tumor uptake and the efficacy of tumor targeting for cancer detection. Original submitted 29 April 2013; Revised submitted 20 September 2013.

PURPOSE: Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment. PATIENTS AND METHODS: Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted. RESULTS: The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET-negative patients. CONCLUSION: On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.

Activity-based costing is used to give a better insight into the actual cost structure of open, transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) supraglottic and total laryngectomies. Cost data were obtained from hospital administration, personnel and vendor structured interviews. A process map identified 17 activities, to which the detailed cost data are related. One-way sensitivity analyses on the patient throughput, the cost of the equipment or operative times were performed. The total cost for supraglottic open (135-203 min), TLM (110-210 min) and TORS (35-130 min) approaches were 3,349 (3,193-3,499 ), 3,461 (3,207-3,664 ) and 5,650 (4,297-5,974 ), respectively. For total laryngectomy, the overall cost were 3,581 (3,215-3,846 ) for open and 6,767 (6,418-7,389 ) for TORS. TORS cost is mostly influenced by equipment (54 %) where the other procedures are predominantly determined by personnel cost (about 45 %). Even when we doubled the yearly case-load, used the shortest operative times or a calculation without robot equipment costs we did not reach cost equivalence. TORS is more expensive than standard approaches and mainly influenced by purchase and maintenance costs and the use of proprietary instruments. Further trials on long-term outcomes and costs following TORS are needed to evaluate its cost-effectiveness.

Serotonin-mediated mechanisms, in particular via the serotonin transporter (SERT), are thought to have an effect on food intake and play an important role in the pathophysiology of obesity. However, imaging studies that examined the correlation between body mass index (BMI) and SERT are sparse and provided contradictory results. The aim of this study was to further test the association between SERT and BMI in a large cohort of healthy subjects. Methods: 127 subjects of the ENC DAT database (58 females, age 52±18 years, range 20-83, BMI 25.2±3.8kg/m(2), range 18.2-41.1) were analysed using region-of-interest (ROI) and voxel-based approaches to calculate [(123)I]FP-CIT specific-to-nonspecific binding ratios (SBR) in the hypothalamus/thalamus and midbrain/brainstem as SERT-specific target regions. Results: In the voxel-based analysis, SERT availability and BMI were positively associated in the thalamus, but not in the midbrain. In the ROI-analysis, the interaction between gender and BMI showed a trend with higher correlation coefficient for men in the midbrain albeit not significant (0.033SBRm(2)/kg, p=0.1). Conclusions: The data are in agreement with previous PET findings of an altered central serotonergic tone depending on BMI, as a probable pathophysiologic mechanism in obesity, and should encourage further clinical studies in obesity targeting the serotonergic system.

Articular cartilage defects are prevalent in metacarpo/metatarsophalangeal (MCP/MTP) joints of horses. The aim of this study was to determine and compare the sensitivity and specificity of 3-Tesla magnetic resonance imaging (3-T MRI) and computed tomography arthrography (CTA) to identify structural cartilage defects in the equine MCP/MTP joint. Forty distal cadaver limbs were imaged by CTA (after injection of contrast medium) and by 3-T MRI using specific sequences, namely, dual-echo in the steady-state (DESS), and sampling perfection with application-optimised contrast using different flip-angle evolutions (SPACE). Gross anatomy was used as the gold standard to evaluate sensitivity and specificity of both imaging techniques. CTA sensitivity and specificity were 0.82 and 0.96, respectively, and were significantly higher than those of MRI (0.41 and 0.93, respectively) in detecting overall cartilage defects (no defect vs. defect). The intra and inter-rater agreements were 0.96 and 0.92, respectively, and 0.82 and 0.88, respectively, for CT and MRI. The positive predictive value for MRI was low (0.57). CTA was considered a valuable tool for assessing cartilage defects in the MCP/MTP joint due to its short acquisition time, its specificity and sensitivity, and it was also more accurate than MRI. However, MRI permits assessment of soft tissues and subchondral bone and is a useful technique for joint evaluation, although clinicians should be aware of the limitations of this diagnostic technique, including reduced accuracy.

Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of (89)Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of (89)Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with (89)Zr ((89)Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to (89)Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-(89)Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-(89)Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-(89)Zr was higher, compared with (89)Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The (89)Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes.

AIM: Treatment of locally advanced rectal cancer (LARC) includes preoperative radiation therapy with or without chemotherapy followed by radical surgery, but the clinical outcome is uncertain. A systemic review was carried out to determine the predictive value of (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in LARC. METHOD: A literature search (PubMed/MEDLINE, EMBASE, Cochrane) up to January 2012 to identify full papers with sequential (18)FDG-PET and survival data, using indexing terms and free text words. The inclusion criteria were: a study of at least 10 patients, having sequential (18)FDG-PET imaging before and after adjuvant chemoradiation and a minimal follow-up of 24 months. Studies were selected by two of the authors. A meta-analysis was performed for DFS and OS using the hazard ratio (HR) as the primary outcome. RESULTS: Five eligible studies were identified including 330 patients (mean age 63 years, 64% men), in which PET-CT or PET imaging was used. The American Joint Committee on Cancer stage distribution was as follows: Stage I, 2%; Stage II, 44%; Stage III, 52%; Stage IV, 1%. The pooled HRs for complete metabolic response versus partial or no response were 0.39 (95% CI 0.18-0.86; P = 0.02) for OS and 0.70 (95% CI 0.16-3.14; P = 0.64) for DFS. The lack of significance for DFS might be explained by different follow-up characteristics. There was also clinical heterogeneity among the different studies. CONCLUSION: This systematic review indicates that complete metabolic response on sequential (18)FDG-PET data after preoperative chemoradiation of LARC is predictive of OS, but not of DFS.

This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.

BACKGROUND: Medication-related harm can be detected using the adverse drug event (ADE) trigger tool and the medication module of the Global Trigger Tool (GTT) developed by the Institute for Healthcare Improvement (IHI). In recent years, there has been some controversy on the performance of this method. In addition, there are limited data on the performance of the medication module of the GTT as compared with the ADE trigger tool. OBJECTIVES: To evaluate the performance of the ADE trigger tool and of the medication module of the GTT for identifying ADEs. METHODS: The methodology of the IHI was used. A random sample of 20 adult admissions per month was selected over a 12-month period in a teaching hospital in Belgium. The ADE trigger tool was adapted to the Belgian setting and included 20 triggers. The positive predictive value (PPV) of each trigger was calculated, as well as the proportion of ADEs that would have been identified with the medication module of the GTT as compared with the ADE trigger tool. RESULTS: A total of 200 triggers and 62 ADEs were found, representing 26 ADEs/100 admissions. Nineteen ADEs (31%) were found spontaneously without the presence of a trigger. Three triggers never occurred. The PPVs of other triggers varied from 0 to 0.67, with half of them having PPVs less than 0.20. If we had used the medication triggers included in the GTT (n = 11), we would have identified 77% of total ADEs and 67% of preventable ADEs. CONCLUSIONS: Applying the trigger tool method proposed by the IHI to a Belgian hospital led to the identification of one ADE out of 4 admissions. To increase performance, refining the list of triggers in the ADE trigger tool and in the medication module of the GTT would be needed. Recording nontriggered events should be encouraged.

Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Gold nanoparticles ([similar]5 nm) coated with plasma-polymerized allylamine were produced through plasma vapor deposition and bioconjugated with a monoclonal antibody targeting the epidermal growth factor receptor. The resulting nanoconjugates displayed an antibody loading of about 1.7 nmol mg−1 and efficiently target epidermal growth factor receptor overexpressing cell lines, as ascertained by ELISA and Western blot assays. The in vitro targeting properties were also confirmed in vivo, where a similar biodistribution profile of what was experienced for the unconjugated antibody was observed. Thanks to the possibility of doping the gold nanoparticles with radionuclides during plasma vapor deposition, the proposed functionalization strategy represents a very suitable platform for the in vivo cancer targeting with nanosized multifunctional particles.

A framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database.

Extramedullary relapse of acute myeloid leukemia (AML) after stem-cell transplant is very rare and often remains a diagnostic challenge. Although the diagnostic value of PET/CT has not been evaluated thoroughly in leukemia, it might be useful for detecting these focal localizations. We presented a case of a 58-year-old man, with a prior history of localized bladder cancer and a secondary AML, referred to our hospital with important thoracic backaches. PET/CT revealed the presence of meningeal carcinomatosis at the thoracic level, as well as lymph nodes, and muscular and bone metastases. Immunophenotyping of the cerebrospinal fluid aspirate showed a relapse of AML.

Nanoscale materials are used in the biomedical field for magnetic resonance imaging, protein detection and drug/gene delivery. Gold nanoparticles (AuNPs) are particularly investigated in cancer treatment and imaging. In this study, we described a simple and reliable liquid method to coat AuNPs (diameter: 21 nm) layer-by-layer with alternative cationic polyallylamine and anionic polystyrenesulfonate. The C-terminal amino acid of the antibody directed against anti-bovine serum albumin was activated by EDC/NHS, and then condensed with the amino functions of the external polyallylamine layer. An ELISA test confirmed that the antigen recognition of the bioconjugate antibody was conserved. This AuNP coating and the covalently coupling could be used as a generic process for binding other specific antibodies, particularly those overexpressed in cancer cells and angiogenesis.

In this work, we investigate the surface reactivity of substrates coated with thin layers (estimated thickness ≤ 30 nm) of plasma polymerized allylamine films (PPAA), an amine-functionalized polymer deposited by plasma-enhanced chemical vapor deposition (PECVD) with radiofrequency (RF) discharges. Our results show that very thin layers, or islands, can retain on their surface molecules that are able to react through their NH2 functions. We have tested and assessed by X-Ray Electron Spectroscopy (XPS) and Quartz Crystal Microbalance (QCM) the surface density of chemical functions vs. layer thicknesses by using chemical derivatization with two types of agents: imine formation by a reaction of primary amine from the coating with aldehyde (Pentafluorobenzaldehyde, PFBA) and amide-bond formation by reaction with an activated carboxylic group (Succinimidyl Succinate Terminated Polyethylene glycol, EGSS). Results show that the PPAA coatings—even for very thin layers of a few nanometers—promote the chemisorption of the tagging molecules. The aging under air and evolution of reactive amine surface concentration with time under air are also presented.

This paper presents the results of the production of carbon nanoparticles by magnetron sputtering inside a gas aggregation tube of fixed dimension, placed vertically in a high vacuum chamber. The nanoparticles are negatively charged, and their morphology was studied according to the positive biasing of a substrate holder. The carbon nanostructures were deposited on formvar grids to be analyzed by transmission electron microscopy. For positive bias voltages larger than 30 V, results showed spherical and randomly dispersed nanoparticles with a mean diameter, which varied from about 10 nm to 20 nm depending on the choice of plasma parameters. By contrast, if the bias voltage was grounded or was lower than or equal to 30 V, only nanoribbon-like structures mixed with compact or fractal groups of nanoparticles were observed on TEM grids. Results are discussed in terms of a 3-step process inside the aggregation tube: nucleation, coalescence and agglomeration of negatively charged nanoparticles.