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Halil Yildiz,1 Diego Castanares-Zapatero,2 Philippe d’Abadie,3 Sarah Bailly,4 Jean Cyr Yombi1 1Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, UClouvain, Bruxelles, Belgium; 2Department of Intensive Care, Cliniques Universitaires Saint-Luc, UClouvain, Bruxelles, Belgium; 3Department of Nuclear Medicine, Cliniques Universitaires Saint-Luc, UClouvain, Bruxelles, Belgium; 4Department of Hematology, Cliniques Universitaires Saint-Luc, UClouvain, Bruxelles, BelgiumCorrespondence: Halil Yildiz, Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, UClouvain, 10 Av Hippocrate, Bruxelles, 1200, Belgium, Email halil.yildiz@saintluc.uclouvain.beIntroduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease, which can be primary (due to genetic mutation) or secondary to malignancy, infection and rheumatologic diseases. Data concerning Belgian patients with adult HLH are lacking.Methods: This retrospective study was performed in a teaching hospital in Belgium. All cases of adult HLH, from December 2010 to April 2022, were reviewed. Patients with more than five HLH-2004 criteria and/or HScore > 80% were included in the study. The objective of our study was to describe clinical and biological characteristics of patients with HLH and attempt to look for variables associated with mortality.Results: Fifty-two patients were included in the final analysis. Mean age (SD) of patients was 48 (18) years old, and 29 patients were of male gender (56%). The underlying diseases associated with HLH were malignancy (M-HLH) in 22 patients, infection related HLH in 20 patients, rheumatologic disease related HLH in 7 patients, idiopathic in 2 patients and secondary to pregnancy in 1 patient. Overall mortality, mortality at 30 days and 90 days were 24/52 (46%), 13/52 (25%) and 4/52 (10%), respectively. In univariate analysis, malignancy, male sex, age and disseminated intravascular coagulation (DIC) were associated with mortality (p < 0.05). In multivariate analysis, only age was significantly associated with mortality (odds ratio, 1.053; 95% confidence interval, 1.016– 1.092; p 0.005).Conclusion: In our study, the most frequent triggers were malignancy and infectious agent followed by rheumatologic disease. Risk factors for mortality were age, male sex, malignancy and DIC, but only age remained significant in multivariate analysis. Treatment guidelines are mainly based on pediatric patients, and it is important for physician to describe adult patients’ outcome to better understand this disease and adapt treatment.Keywords: hemophagocytic lymphohistiocytosis, macrophage activation syndrome, infection, autoimmune disease, malignancy, corticosteroid, tocilizumab, ruxolitinib, mortality

AIM: The manufacturers' recommended methods to calculate delivered activities in liver radioembolization are simplistic and only slightly personalized. Activity planning could also be based on a 99mTc-macroaggregated albumin SPECT/CT (MAA) using the partition model but its accuracy is controversial. This study evaluates the dose parameters in the normal liver and in the tumor compartments using MAA SPECT/CT (pre-therapeutic imaging) and 90Y TOF-PET/CT (post-therapy imaging). Finally, we propose a prescription of the activity as a function of the normal liver MAA distribution. METHOD: 66 procedures of RE (with resin microspheres) corresponding to 171 lesions were analyzed. Tumor to normal targeted liver uptake (T/NTL), tumor absorbed dose (TD) and whole normal liver absorbed (WNLD) were assessed with MAA and 90Y imaging. Secondly, activities were recalculated using the MAA distribution in the normal liver compartment to reach the maximal tolerable liver dose. These Activities were compared to activities defined with the BSA method. RESULTS: Compared to 90Y imaging, our study demonstrated an accurate estimation of the WNLD using MAA imaging (Pearson's R = 0.97, p < 0.001). On the contrary, significant variations were found for TD (R = 0.65, p < 0.001). The MAA T/NTL ratio has a 85% positive predictive value in identifying patients who will get a 90Y T/NTL ratio above 1.5. Moreover, activities calculated using the MAA distribution in the normal liver compartment were significantly higher to activities defined with the BSA method. CONCLUSION: Whole normal liver absorbed doses are accurately predicted with MAA imaging and could be used to optimize the activity planning.

Selective internal radiation therapy (SIRT) is one of the treatment options for liver tumors. Microspheres labelled with a therapeutic radionuclide (90Y or 166Ho) are injected into the liver artery feeding the tumor(s), usually achieving a high tumor absorbed dose and a high tumor control rate. This treatment adopts a theranostic approach with a mandatory simulation phase, using a surrogate to radioactive microspheres (99mTc-macroaggregated albumin, MAA) or a scout dose of 166Ho microspheres, imaged by SPECT/CT. This pre-therapy imaging aims to evaluate the tumor targeting and detect potential contraindications to SIRT, i.e., digestive extrahepatic uptake or excessive lung shunt. Moreover, the absorbed doses to the tumor(s) and the healthy liver can be estimated and used for planning the therapeutic activity for SIRT optimization. The aim of this review is to evaluate the accuracy of this theranostic approach using pre-therapy imaging for simulating the biodistribution of the microspheres. This review synthesizes the recent publications demonstrating the advantages and limitations of pre-therapy imaging in SIRT, particularly for activity planning.

A 54-year-old man with a history of tonsillar squamous cell carcinoma treated with chemoradiotherapy and an 18-year history of seropositive rheumatoid arthritis in remission without maintenance therapy presented with right cervical pain and dysphagia for several months. Flexible laryngoscopy did not show any lesion, and MRI revealed a necrotic lesion inside the thyro-hyo-epiglottic space attached to the hyoid bone. 18 F-FDG PET/CT demonstrated a moderately increased metabolic activity of the lesion without any other suspected lesions. Surgical resection was performed, and pathology revealed a necrotizing granuloma compatible with a rheumatoid nodule.

AIM 90Y-radioembolization using glass or resin microspheres is increasingly used for the treatment of hepatocellular carcinoma (HCC). The aim of this retrospective study is to determine the prognostic relevance of dosimetric parameters defined with 90Y-PET-CT obtained immediately after radioembolization. METHODS Forty-five HCC patients, mostly with multiple lesions, were treated by radioembolization between 2011 and 2017. After treatment, all underwent a 90Y PET-CT with time of flight reconstruction (90Y-TOF-PET-CT). Tumor absorbed dose and cumulative tumor dose-volume histogram were calculated using a dose point Kernel convolution algorithm. The radiological tumor response was assessed using modified (m)-RECIST criteria. Progression-free-survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS Twenty-six patients were treated with glass microspheres (73 lesions) and nineteen with resin microspheres (60 lesions). Thresholds of 118 and 61 Gy for glass and resin microspheres respectively correlate well with radiological response with a positive predictive value (PPV) of 98 and 80% and discriminate patient outcome with regard to PFS (P = 0.03 and 0.005) and OS (P = 0.003 and 0.007). Using dose volume histogram, a minimal absorbed dose of 40 Gy in 66% of the tumor volume (defined as D66) was highly predictive of radiological response (PPV = 94%), PFS (P < 0.001) and OS (P = 0. 008), for either device. CONCLUSION Dosimetric parameters obtained using 90Y-PET-CT are predictive of tumor response, PFS and OS. In clinical practice, a systematic dosimetric evaluation using 90Y PET should be implemented to help predicting patient outcomes.

Background: Tumor equivalent uniform dose (EUD) is a predictor of patient outcome after selective internal radionuclide therapy (SIRT) of hepatocellular carcinoma (HCC) and can be evaluated with 90Y-TOF-PET. The aim is to evaluate the correlation between PET based tumors EUD and the clinical response evaluated with dual molecular tracer (11C-acetate and 18F-FDG) PET/CT post SIRT. Methods: 34 HCC tumors in 22 patients were prospectively evaluated. The metabolic response was characterized by the Total Lesion Metabolism variation (ΔTLM) between baseline and follow up. This response allowed to compute a Tumor Control Probability (TCP) as a function of the tumor EUD. Results: The dose response correlation was exponential-asymptotic shaped and highly significant (R=0.72, P < 0.001). With a cutoff of 40Gy, the metabolic response was strongly different in both groups (median response 35% versus 100%, p< 0.001). Moreover, the TCP (EUD) was very similar to that observed in External Beam Radiation Therapy (EBRT). Conclusions: EUD based 90Y TOF-PET/CT predicts the metabolic response after SIRT of HCC assessed using dual molecular PET tracers and provides a similar TCP curve to that observed in EBRT. Both TCPs show that a EUD of 100 Gy is needed and sufficient to control a HCC.

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

PURPOSE: We aimed to determine whether antireflux (ARC) catheter may result in better tumor targeting in liver radioembolization using (90)Y-resin microspheres. METHODS: Patients treated with resin microspheres for hepatocellular carcinoma (HCC) and secondary liver malignancies were retrospectively analyzed. All patients underwent a (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) single photon emission computed tomography (SPECT) following the planning arteriography with a conventional end-hole catheter. For (90)Y-microspheres injection, two groups were defined depending on the type of catheter used: an ARC group (n=38) and a control group treated with a conventional end-hole catheter (n=23). (90)Y positron emission tomography computed tomography (PET/CT) was performed after the therapeutic arteriography. The choice of the catheter was not randomized, but left to the choice of the interventional radiologist. (99m)Tc-MAA SPECT and (90)Y PET/CT were co-registered with the baseline imaging to determine a tumor to normal liver ratio (T/NL([MAA or 90Y])) and tumor dose (TD([MAA or 90Y])) for the planning and therapy. RESULTS: Overall, 38 patients (115 lesions) and 23 patients (75 lesions) were analyzed in the ARC and control groups, respectively. In the ARC group, T/NL(90Y) and TD(90Y) were significantly higher than T/NL(MAA) and TD(MAA). Median (IQR) T/NL(90Y) was 2.16 (2.15) versus 1.74 (1.43) for T/NL(MAA) (p < 0.001). Median (IQR) TD(90Y) was 90.96 Gy (98.31 Gy) versus 73.72 Gy (63.82 Gy) for TD(MAA) (p < 0.001). In this group, the differences were highly significant for neuroendocrine metastases (NEM) and HCC and less significant for colorectal metastases (CRM). In the control group, no significant differences were demonstrated. CONCLUSION: The use of an ARC significantly improves tumor deposition in liver radioembolization with resin microspheres.

Breast cancer is the most common malignancy occurring in women worldwide. More than 90% of patients present with localized disease are treated with curative intent; however, recurrence can occur with development of metastatic lesions. Frequently associated with extra-hepatic lesions, localized treatments (surgery or stereotaxic body radiotherapy) are rarely proposed in liver lesions. 90Y radioembolization has extensively been evaluated in colorectal cancer, but its role in breast cancer with isolated liver metastases remains largely unknown. Pre-existing liver diseases are known risk factors for 90Y induced liver toxicity. Not considered as an excluding factor for this treatment, data are limited regarding its safe use with cholangitis. We report a successful control of liver metastases by 90Y radioembolization in a breast cancer patient., Lay abstract Breast cancer is the most common malignancy occurring in women worldwide. Metastasis-directed therapies are more and more often offered to patients in order to delay systemic treatments; however, their role in improving survival remains unknown. Trans-arterial radioembolization with 90Y appears to be an interesting strategy in breast cancer with isolated liver metastases, even if its survival benefit remains largely unknown. Safety of trans-arterial radioembolization also remains under investigated in patients with previous liver disease. We report a successful control of liver metastases by 90Y radioembolization in a breast cancer patient.

Simple Summary Radioembolization of hepatic tumors is performed by injecting 90Y or 166Ho loaded spheres into the hepatic artery. A twofold tumor to normal liver absorbed dose ratio is commonly obtained. In order to improve tumoral cell killing while preserving lobule function, co-injection of arterial vasoconstrictor has been proposed, but without success: the hepatic arterial buffer response quickly inhibits the arterioles vasoconstriction. The aim of the study is to investigate whether it is possible to take benefit from this buffer response, by co-infusing a mesenteric arterial vasodilator in order to dump the hepatic lobules arterial flow. Animal studies evidencing such mechanism are reviewed. Some potential mesenteric vasodilators are identified and their safety profile discussed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in hepatocellular carcinoma (HCC), more frequent in obese subjects, and where ultra-selective spheres delivery is often not possible. Abstract Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.

Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, 90Y and 166Ho. The relationship between the microspheres’ properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.

Bulletin reprenant les principales publications concernant le corpus biblique indiqué. A. Wénin est l'auteur de la 2e section intitulée "Études narratives et synchroniques".

Primary cutaneous apocrine adenocarcinoma (PCAC) is an extremely rare neoplasm involving the sweat glands. Due to a lack of cases, there is no consensus for the systemic treatment of locally advanced or metastatic PCAC. Anti‐androgen therapy may have activity in inoperable or metastatic PCAC with high androgen receptor (AR) expression.

Face a un modele « exodique », herite des milieux de l'exil, que l'on retrouve notamment dans l'historiographie deuteronomiste ou dans le livre d'Esdras-Nehemie, le Chroniste propose une histoire c...

We present an unusual case of cardiac tamponade in a 17-year-old girl immunocompetent patient due to Salmonella enterica ssp. bredeney following infection of a bronchogenic cyst. The patient was admitted to hospital with pleuritic chest pain, dyspnoea and fever. Pulmonary angio-CT showed a bronchogenic cyst compressing the left atrium. The echocardiography showed diffuse pericardial effusion with right ventricular collapse consistent with cardiac tamponade. Pericardiocentesis was performed and microbiological cultures of the pericardial fluid became positive for Salmonella species confirmed later as bredeney subspecies by PCR. Empirical antibiotherapy was started with intravenous (IV) ceftriaxone. Bronchogenic cyst infection was suspected and confirmed by 18FDG PET CT. The patient was successfully treated by complete resection of the cyst and continuation of IV ceftriaxone followed by oral amoxicillin/clavulanate for a total duration of 6 weeks. She then completely recovered and didn't present any relapse after 6 months of follow up.

A 53-year-old female underwent a lung ventilation/perfusion scintigraphy (V/Q scan) in the workup of extensive thrombosis of the left subclavian and internal jugular veins. The perfusion lung scan visualized an atypical uptake in the thoracic vertebrae. A chest Computed Tomography (CT) scan demonstrated unusual tortuous and opacified thoracic superficial veins, collaterals of the lateral thoracic vein. Many venous collateral pathways can be developed in the case of superior vena cava syndrome.99mTc-macroaggregated albumin particles may pass through the lateral thoracic vein and eventually through the vertebral venous plexus before being finally trapped by the vertebral capillaries. Besides right-to-left shunting, extrapulmonary uptake in the lung perfusion scintigraphy is very rare and may be used by collateral venous pathways.

A 26-year-old man was referred to the ophthalmology department with a 1-week history of blurred vision of the left eye; there was no pain or redness. Ophthalmological examination found unilateral choriocapillaropathy with optic nerve oedema. He was in a stable relationship and had not travelled abroad recently, nor had he been in contact with any animals or pets. He had a history of ulcerative colitis diagnosed 2 years earlier for which he was treated for 1 year with azathioprine and oral corticosteroids. Since then he had been totally asymptomatic. [...]

Apres avoir montre l’heritage de l’historiographie perse dans l’historiographie judeenne des IV-IIIe siecles av. J.-C., l’auteur met en lumiere la maniere dont les livres d’Esdras-Nehemie d’un cote, et des Chroniques de l’autre, ont cherche a definir l’identite judeenne par le biais d’une ecriture historiographique. Au final se dessinent deux apprehensions fort differentes de cette realite, alors meme que ces livres usent abondamment de schemas scripturaires empruntes aux livres de la Torah et des Prophetes, a travers continuite et rupture.

Il est encore paradoxal de reconnaitre aux livres des Chroniques le statut d’œuvre litteraire. Longtemps considere comme de « pietre fiabilite » par rapport au recit parallele des livres de Samuel et des Rois, ces livres apparaissent aussi sans originalite litteraire par rapport notamment a l’art consomme des recits des livres de Samuel. Dans le sillage de L’Art du recit biblique de Robert Alter, Ph. Abadie tente de faire ressortir la richesse et la variete des procedes d’ecriture qui font du livre des Chroniques une œuvre litteraire veritable. Celle-ci tient fondamentalement a un projet global que revelent et confirment des « unites kerygmatiques » structurantes et l’ordonnancement de grands ensembles selon divers procedes : technique de repetition et systeme de periodisation chronologique notamment.

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