[Immunotherapy for bladder cancer in 2021]. / Immunothérapie dans le cancer de la vessie : mise à jour 2021.

Intravesical immunotherapy with Calmette-Guerin bacillus (BCG) have been used since decades for the treatment of non-muscle invasive bladder cancer and is a proof of principle that immunotherapy works for this malignancy. Since 2016, immune checkpoint inhibitors (ICI) demonstrated clinical benefits in locally advanced or metastatic bladder cancer, providing potentially durable tumor control in first line therapy or upon relapse after standard treatments. Ongoing clinical trials aim to demonstrate the efficiency of ICI for the treatment of localized disease.

L'immunothérapie par instillation de bacille de Calmette-Guérin est utilisée depuis plusieurs décennies dans le cancer de la vessie non musculo-invasif. Cette forme d'immunothérapie locale est témoin de l'efficacité de cette approche thérapeutique. Depuis 2016, les inhibiteurs de points de contrôle immunitaire (IPCI) complètent l'arsenal thérapeutique notamment lors d'une maladie localement avancée ou métastatique. Ils permettent d'obtenir des résultats bénéfiques potentiellement durables en première ligne de traitement et après échec des traitements standards. Des efforts sont en cours afin de démontrer le bénéfice des IPCI dans la prise en charge de la maladie localisée.

[Breast cancer during pregnancy]. / Cancer du sein chez la femme en.

The management of patients with breast cancer during their pregnancy is challenging. A good coordination is required between the oncology and obstetrics teams in order to ensure appropriate care, while providing a reassuring environment during this stressful period. Most often, the pregnancy can continue without delaying the initiation of oncological treatments, offering a prognosis similar to non-pregnant women. Surgery and chemotherapy can be done during pregnancy, unlike endocrine therapy, radiotherapy and antibody treatments which can only be given postpartum. While some imaging techniques are compatible, others require special measures or are contraindicated. We discuss these points in the context of a clinical situation.

La prise en charge des patientes présentant un cancer du sein durant leur grossesse est un challenge. Elle exige une bonne coordination entre les équipes oncologique et obstétricale afin d'assurer des soins appropriés tout en offrant un cadre rassurant en cette période de grand stress. Le plus souvent, la grossesse peut être poursuivie sans retarder l'initiation des traitements oncologiques, avec un pronostic similaire aux femmes non enceintes. La chirurgie et la chimiothérapie peuvent être entreprises en cours de grossesse, contrairement à l'hormonothérapie, la radiothérapie et les traitements par anticorps qui ne peuvent être administrés qu'en post-partum. Si certaines techniques d'imagerie sont compatibles, d'autres requièrent des mesures particulières ou sont contre-indiquées. Nous discutons de ces points dans le cadre d'une situation clinique.

[Immune-related adverse events of checkpoint inhibitors: an internist/general practitioner's point of view]. / Effets indésirables immunomédiés des inhibiteurs de points de contrôle immunitaire: point de vue de l'interniste.

Immune checkpoint inhibitors have radically changed oncology by significantly improving prognosis and survival of many patients, even at an advanced or metastatic stage. Some patients undergoing immunotherapy develop adverse immune-related events, presenting a toxicity spectrum that can affect any organ, separately or simultaneously, with different intensities depending on the treatment used and patient characteristics. We hereby suggest a diagnostic and therapeutic approach that any internist, general practitioner or emergency doctor should have facing digestive, cardiac and pulmonary toxicities.

Les inhibiteurs de points de contrôle immunitaire (IPCI) ont radicalement changé la prise en charge oncologique en améliorant significativement le pronostic ainsi que la survie de nombreux patients, même à un stade avancé ou métastatique. Une partie des patients traités peuvent développer des effets indésirables immunomédiés avec un spectre de toxicités pouvant atteindre tous les organes, de façon isolée ou simultanée, avec une sévérité et une chronologie variables en fonction du traitement utilisé et des caractéristiques de chaque patient. Nous proposons ici la conduite à tenir du médecin interniste, généraliste ou urgentiste devant les toxicités digestives, cardiaques et pulmonaires.

[Management of peripheral neuropathy in the elderly]. / Prise en charge des polyneuropathies sensitives chez la personne âgée.

Polyneuropathies occur frequently (> 30 %) among elderly people and can result in increased morbidity and impaired quality of life. Diabetes, chronic kidney disease, water-soluble vitamins deficiencies, drugs and alcohol side effects are the major etiologies after a systematic assessment. Neurologist referral is indicated when the diagnosis remains unclear and therapeutic options exist. Treatment strategies focus on reversal of underlying conditions, prevention, stabilization and alleviation of symptoms, especially neuropathic pain and maintain the best autonomy.

Les polyneuropathies sensitives sont observées chez environ 30 % des personnes âgées et sont potentiellement grevées d'une importante morbidité. Une approche systématique permet souvent un diagnostic étiologique : diabète, insuffisance rénale chronique, carences vitaminiques hydrosolubles, effets secondaires médicamenteux et consommation d'alcool en tête. L'avis neurologique est indiqué après un premier bilan négatif, en présence d'options thérapeutiques. Le traitement vise à corriger les étiologies lorsque cela est possible, à prévenir, stabiliser et soulager les symptômes, en particulier la douleur neuropathique, ainsi qu'à préserver la meilleure autonomie possible.

Severe Late-Onset Drug-Induced Immune Thrombocytopenia Following IFN ß-1a Treatment: A Case Report of a 52-Year-Old Woman with Relapse-Remitting Multiple Sclerosis.

Interferon ß-1a (IFNß1a) is considered safe in relapsing-remitting multiple sclerosis (RRMS). Drug-induced thrombocytopenia (DITP) is a rare but underreported adverse event that is often confused with other causes of thrombocytopenia. We report the case of a 52-year-old woman who developed limb and oral mucosa petechiae and hematochezia, 10 years after beginning IFNß1a. Blood work showed an isolated severe thrombocytopenia and ruled out other autoimmune diseases, viral infections, intravascular hemolysis, and renal impairment. Oral corticosteroids and tranexamic acid were initiated with a favorable platelet response. IFNß1a was resumed, leading to recurrence of thrombocytopenia. Platelets came back to normal after intravenous immunoglobulins and IFNß1a was definitively discontinued. To our knowledge, this is the first case of drug-induced immune thrombocytopenia (DITP) associated with IFNß1a.

Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth.

Stem and progenitor cells residing in the intestinal crypts drive the majority of colorectal cancers (CRCs), yet vascular contribution to this niche remains largely unexplored. VEGFA is a key driver of physiological and tumor angiogenesis. Accordingly, current anti-angiogenic cancer therapies target the VEGFA pathway. Here we report that in CRC expansion of the stem/progenitor pool in intestinal crypts requires VEGFA-independent growth and remodeling of blood vessels. Epithelial transformation induced expression of the endothelial peptide apelin, directs migration of distant venous endothelial cells towards progenitor niche vessels ensuring optimal perfusion. In the absence of apelin, loss of injury-inducible PROX1+ epithelial progenitors inhibited both incipient and advanced intestinal tumor growth. Our results establish fundamental principles for the reciprocal communication between vasculature and the intestinal progenitor niche and provide a mechanism for resistance to VEGFA-targeting drugs in CRCs.

DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.

The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature.