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Endocrinology and Metabolism Clinics of... Dec 2021Hypercalcemia of malignancy (HCM) is considered an oncologic emergency associated with significant symptom burden and increased comorbid conditions and mortality.... (Review)
Review
Hypercalcemia of malignancy (HCM) is considered an oncologic emergency associated with significant symptom burden and increased comorbid conditions and mortality. Underlying pathologic processes most often stimulate osteoclast-mediated bone resorption. Although long-term control of HCM depends on effective management of the underlying cancer, temporizing management strategies for acute and/or symptomatic HCM include hydration and antiresorptive bone-modifying agents. Although most patients respond well to the antiresorptive therapies available, further investigation into other agents for those who are refractory to both bisphosphonates and denosumab is needed.
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Hypercalcemia; Neoplasms; Paraneoplastic Syndromes
PubMed: 34774243
DOI: 10.1016/j.ecl.2021.07.003 -
Practical Neurology Feb 2022Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens... (Review)
Review
Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens expressed by the tumour. Classically, well-characterised 'onconeuronal' antibodies target intracellular antigens and hence cannot access their antigens across intact cell membranes. The pathogenic mediators are likely to be neuronal-specific T cells. There is a variable response to immunotherapies and the clinical syndrome helps to direct the search for a specific set of tumours. By contrast, many newly emerging autoantibodies with oncological associations target cell surface epitopes and can exert direct pathogenic effects on both the central and peripheral nervous systems. Patients with these cell-surface directed autoantibodies often clearly respond to immunotherapies. Overall, the clinical, serological and oncological features in an individual patient help to determine the clinical relevance of the syndrome and hence guide its management. We summarise current knowledge and a practical approach to the investigation, diagnosis, treatment and outcomes of patients with suspected PNS.
Topics: Autoantibodies; Humans; Immunotherapy; Paraneoplastic Syndromes, Nervous System
PubMed: 34510016
DOI: 10.1136/practneurol-2021-003073 -
Blood Jul 2014As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly...
As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly important. Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome. However, because early and aggressive immunosuppression could limit the efficacy of the immunotherapy, current approaches seek to limit administration of immunosuppressive therapy to patients at risk for life-threatening consequences of the syndrome. This report presents a novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of CRS based on severity. The goal of our approach is to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of CRS.
Topics: Child; Cytokines; Female; Humans; Immune System Diseases; Leukemia; Paraneoplastic Syndromes; Young Adult
PubMed: 24876563
DOI: 10.1182/blood-2014-05-552729 -
The American Journal of Medicine Aug 2022
Topics: Autoantibodies; Dermatomyositis; Humans; Paraneoplastic Syndromes
PubMed: 35219689
DOI: 10.1016/j.amjmed.2022.01.016 -
The Lancet. Neurology Jan 2024Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling... (Review)
Review
Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. Early diagnosis and initiation of immunosuppressive therapy are likely to be crucial in preventing the accumulation of neurological disability. Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets.
Topics: Humans; Immune Checkpoint Inhibitors; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neoplasms; Autoantibodies
PubMed: 38101905
DOI: 10.1016/S1474-4422(23)00369-1 -
Trends in Cancer Dec 2018Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the... (Review)
Review
Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.
Topics: Antineoplastic Agents; Cachexia; Combined Modality Therapy; Humans; Muscle, Skeletal; Neoplasms; Nutritional Support; Paraneoplastic Syndromes; Quality of Life; Treatment Outcome
PubMed: 30470306
DOI: 10.1016/j.trecan.2018.10.001 -
Internal Medicine (Tokyo, Japan) Jun 2019Autoimmune pancreatitis (AIP) is now considered a pancreatic manifestation of a newly proposed disease condition, IgG4-related disease (IgG4-RD). IgG4-RD is... (Review)
Review
Autoimmune pancreatitis (AIP) is now considered a pancreatic manifestation of a newly proposed disease condition, IgG4-related disease (IgG4-RD). IgG4-RD is characterized by enhanced IgG4 antibody responses and multiple organ involvements. Recent epidemiological studies have addressed the incidence of cancer in patients with AIP and/or IgG4-RD. Surprisingly, a significant number of AIP patients were detected with cancer at or within one year of the diagnosis of AIP. Furthermore, around 50% of all cancers detected in AIP patients comprised mainly 3 types (gastric, lung, and prostate cancer). Thus, AIP appears to be associated with cancer of other organs rather than the pancreas itself, which suggests that AIP is not a pre-cancerous condition of the pancreas. Moreover, the simultaneous occurrence of cancer and AIP in many patients has led to the establishment of an attractive concept that AIP might sometimes arise from co-existing cancers as a paraneoplastic syndrome.
Topics: Acute Disease; Autoimmune Diseases; Humans; Immunoglobulin G4-Related Disease; Incidence; Neoplasms; Pancreatitis; Paraneoplastic Syndromes
PubMed: 30713326
DOI: 10.2169/internalmedicine.2210-18 -
Rheumatic Diseases Clinics of North... Aug 2020Paraneoplastic syndromes are rare diseases caused by malignancies through means other than mass effect or metastasis. Paraneoplastic phenomena can be the first sign of... (Review)
Review
Paraneoplastic syndromes are rare diseases caused by malignancies through means other than mass effect or metastasis. Paraneoplastic phenomena can be the first sign of cancer and can be fatal. Paraneoplastic rheumatic syndromes can occur with hematologic cancers, lymphoproliferative disease, and solid tumors. Diseases that feature an advanced age at onset, significant constitutional upset, inadequate response to treatment, and otherwise atypical characteristics should increase the index of suspicion for a paraneoplastic syndrome.
Topics: Humans; Musculoskeletal Diseases; Neoplasms; Paraneoplastic Syndromes
PubMed: 32631605
DOI: 10.1016/j.rdc.2020.04.002 -
Journal of Internal Medicine Mar 2023Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with... (Review)
Review
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with progressive bone pain, muscle weakness, and fragility fractures. TIO is characterized by hypophosphatemia, excess renal phosphate excretion, and low/inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH) D) levels. Rarity and enigmatic clinical presentation of TIO contribute to limited awareness among the medical community. Accordingly, appropriate diagnostic tests may not be requested, leading to delayed diagnosis and poorer patient outcomes. We have developed a global guidance document to improve the knowledge of TIO in the medical community, enabling the recognition of patients with TIO and appropriate referral. We provide recommendations aiding diagnosis, referral, and treatment, helping promote a global standard of patient management. We reviewed the literature and conducted a three-round Delphi survey of TIO experts. Statements were drafted based on published evidence and expert opinions (≥70% consensus required for final recommendations). Serum phosphate should be measured in patients presenting with chronic muscle pain or weakness, fragility fractures, or bone pain. Physical examination should establish features of myopathy and identify masses that could be causative tumors. Priority laboratory evaluations should include urine/serum phosphate and creatinine to assess renal tubular reabsorption of phosphate and TmP/GFR, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25(OH) D, and FGF23. Patients with the clinical/biochemical suspicion of TIO should be referred to a specialist for diagnosis confirmation, and functional imaging should be used to localize causative tumor(s). Recommended treatment is tumor resection or, with unresectable/unidentifiable tumors, phosphate salts plus active vitamin D, or burosumab.
Topics: Humans; Phosphates; Hypophosphatemia; Paraneoplastic Syndromes; Fractures, Bone; Pain; Fibroblast Growth Factors
PubMed: 36511653
DOI: 10.1111/joim.13593 -
Advances in Chronic Kidney Disease Mar 2022Paraneoplastic glomerular diseases (GNs) are rare manifestations in patients with underlying hematologic and solid organ malignancies and can occur before or after the... (Review)
Review
Paraneoplastic glomerular diseases (GNs) are rare manifestations in patients with underlying hematologic and solid organ malignancies and can occur before or after the detection of cancer. In the absence of established algorithms for investigation and reliable tests, they remain difficult to diagnose. Given the heterogeneity and infrequency of cases, the pathogenesis of most paraneoplastic GNs is poorly understood. Most of our recent understanding of paraneoplastic GNs has emerged from the discovery of target antigens in membranous nephropathy such as thrombospondin type-1 domain-containing protein 7A and neural epidermal growth factor-like 1 protein that appear to be promising in differentiating a primary vs paraneoplastic cause of membranous nephropathy. Treatment of paraneoplastic GNs is usually directed at the underlying malignancy. This review will focus on the epidemiology, pathogenesis, and diagnosis of paraneoplastic glomerular processes.
Topics: Autoantibodies; Glomerulonephritis, Membranous; Humans; Kidney Glomerulus; Neoplasms; Paraneoplastic Syndromes
PubMed: 35817519
DOI: 10.1053/j.ackd.2022.02.009