Nivolumab-Induced Cytokine Release Syndrome: A Case Report and Literature Review.

BACKGROUND CRS (cytokine release syndrome) is a massive activation of the inflammatory system characterized by a supra-physiological rate of inflammatory cytokines. The interleukin 6 cytokine plays a central role in CRS. The main clinical sign of CRS is fever, but CRS can lead to multiple organ failure in severe cases. CRS is usually described in sepsis, more recently in SARS COV-2 infection, and in chimeric antigen receptor T-cell therapy. However, it can also be associated with immune checkpoint inhibitors (ICIs), which is infrequently described. ICI have growing indications and can lead to CRS by causing an uncontrolled activation of the immune system. There are currently no treatment guidelines for ICI-induced CRS. CASE REPORT We report a rare case of grade 3 CRS induced by nivolumab associated with 5-fluorouracil and oxaliplatin for gastric cancer. The patient was 65-year-old man with an adenocarcinoma of the cardia. CRS developed during the tenth course of treatment and was characterized by fever, hypotension requiring vasopressors, hypoxemia, acute kidney injury, and thrombopenia. The patient was transferred quickly to the Intensive Care Unit. He was treated for suspected sepsis, but it was ruled out after multiple laboratory examinations. There was rapid resolution after infusion of hydrocortisone. CONCLUSIONS The use of ICIs is expanding. Nivolumab-induced CRS is rarely described but can be severe and lead to multiple organ dysfunction; therefore, intensive care practitioners should be informed about this adverse effect. More studies are needed to better understand this condition and establish treatment guidelines.

Budget-Friendly Generation, Biochemical Analyses, and Lentiviral Transduction of Patient-Derived Colon Organoids.

For the past decade, three-dimensional (3D) culture models have been emerging as powerful tools in translational research to overcome the limitations of two-dimensional cell culture models. Thanks to their ability to recapitulate the phenotypic and molecular heterogeneity found in numerous organs, organoids have been used to model a broad range of tumors, such as colorectal cancer. Several approaches to generate organoids exist, with protocols using either pluripotent stem cells, embryonic stem cells, or organ-restricted adult stem cells found in primary tissues, such as surgical resections as starting material. The latter, so-called patient-derived organoids (PDOs), have shown their robustness in predicting patient drug responses compared to other models. Because of their origin, PDOs are natural offspring of the patient tumor or healthy surrounding tissue, and therefore, have been increasingly used to develop targeted drugs and personalized therapies. Here, we present a new protocol to generate patient-derived colon organoids (PDCOs) from tumor and healthy tissue biopsies. We emphasize budget-friendly and reproducible techniques, which are often limiting factors in this line of research that restrict the development of this 3D-culture model to a small number of laboratories worldwide. Accordingly, we describe efficient and cost-effective techniques to achieve immunoblot and high-resolution microscopy on PDCOs. Finally, a novel strategy of lentiviral transduction of PDCOs, which could be applied to all organoid models, is detailed in this article. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Establishment of PDCOs from biopsies Basic Protocol 2: Long-term maintenance and expansion of PDCOs in BME domes Basic Protocol 3: Cryopreservation and thawing of PDCOs Basic Protocol 4: Lentiviral transduction of PDCOs Basic Protocol 5: Immunoblot and evaluation of variability between donors Basic Protocol 6: Immunofluorescence labeling and high-resolution microscopy of PDCOs Basic Protocol 7: Transcriptomic analyses of PDCOs by RT-qPCR.

Aggressive recurrent respiratory papillomatosis: A series of five consecutive patients successfully treated with adjuvant intravenous bevacizumab. A single Belgian academic center experience.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a currently incurable benign neoplasm caused by human papilloma virus (HPV) infection. It usually reduces voice, respiratory, and general quality of life, and is sometimes life-threatening. Patients usually need repeated operations. The use of adjuvant bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has been described in several case reports, with a good efficacy and safety profile. METHODS: We report the cases of five patients with aggressive RRP who were treated with adjuvant systemic bevacizumab in a single Belgian tertiary center. RESULTS: A complete response was achieved in four patients after a median of 4.5 months, and a partial response in one. In all cases, the number of surgeries was drastically reduced, and quality of life improved. Toxicity was easily managed. CONCLUSIONS: Systemic bevacizumab seems to be an effective and safe adjuvant treatment for aggressive RRP.

Preoperative treatment of benign insulinoma: diazoxide or somatostatin analogues?

Surgery is the ideal treatment of insulinoma. However, systemic therapy may be required to prevent severe preoperative hypoglycaemia, when surgery is contraindicated, delayed or refused and in case of unresectable metastatic disease. Diazoxide is commonly used but is not always effective and can cause serious side effects. Somatostatin analogues (octreotide and lanreotide) may be an alternative option. We report the case of a 27-year-old patient with insulinoma in whom diazoxide was compared with lanreotide before operation. A diagnosis of insulinoma was made on the basis of a fasting test and a 2 cm tumour confirmed in the body of the pancreas, with a high uptake of 111-In-pentreotide. Diazoxide was initiated and increased to a maximal tolerated dose of 450 mg/day. Because of dyspnoea and persisting hypoglycaemia, diazoxide was shifted to lanreotide 120 mg. All symptoms resolved without hypoglycaemia. According to the EORTC quality score of life, the score without treatment, under diazoxide, under lanreotide and after surgery were respectively 84.7, 73.3, 90.9 and 99.1. Thus, providing a positive Octreoscan, somatostatin analogues may be a safe, effective and well-tolerated option in patients with insulinoma refractory and/or intolerant to diazoxide or with a high risk of fluid retention.

Incidence and Prognosis of Biliary Tract and Gallbladder Cancers in a Belgian Academic Hospital.

BACKGROUND: Biliary tract and gallbladder cancers are rare tumors with a poor prognosis (except the ampulla type). The evolution of hepatobiliary cancer incidence varies widely around the world. According to the Belgian Cancer Registry, the number of hepatobiliary cancers has increased every year since 2004. MATERIALS AND METHODS: This retrospective study included patients diagnosed with cholangiocarcinoma, ampulla cancer, or gallbladder cancer at the university hospital, CHU UCL, Godinne site, in Namur, Belgium, between 1997 and 2017. The evolution of cancer incidence was evaluated with the Mann-Kendall method, by analyzing 7 consecutive 3-year periods. We calculated survival with the Kaplan-Meier method, and we determined prognostic factors with the log-rank test and Cox models. RESULTS: Between 1997 and 2017, we included 128 patients that were newly diagnosed in our center. According to the Mann-Kendall test, the evolution of the incidence of these cancers in our hospital increased significantly over the study period (Sen's slope = 7; p = 0.003). The 1-year overall survival was 53.0 ± 4.7%. Poor prognostic factors included age, cancer stage, local cancer extension, and metastatic disease. The independent prognostic factors of survival were age (p = 0.002), ampulla cancer (p < 0.001), and metastatic disease (p < 0.001). CONCLUSIONS: We found that the incidence of biliary tract and gallbladder cancers increased over a period of 20 years in our center. Further investigations are needed to determine the reasons for this increase. Although new therapies are emerging, the prognosis remains poor for these cancers. Determining risk factors might promote the development of preventive approaches.