Project description:Tumor lysis syndrome (TLS) is an oncologic emergency triggered by the rapid release of intracellular material from lysing malignant cells. Most common in rapidly growing hematologic malignancies, TLS has been reported in virtually every cancer type. Central to its pathogenesis is the rapid accumulation of uric acid derived from the breakdown of nucleic acids, which leads to kidney failure by various mechanisms. Kidney failure then limits the clearance of potassium, phosphorus, and uric acid leading to hyperkalemia, hyperphosphatemia, and secondary hypocalcemia, which can be fatal. Prevention of TLS may be more effective than treatment, and identification of at-risk individuals in whom to target preventative efforts remains a key research area. Herein, we discuss the pathophysiology, epidemiology, and treatment of TLS with an emphasis on the kidney manifestations of the disease.
Project description:BackgroundThe pathophysiology of AKI during tumor lysis syndrome (TLS) is not well understood due to the paucity of data. We aimed to decipher crystal-dependent and crystal-independent mechanisms of TLS-induced AKI.MethodsCrystalluria, plasma cytokine levels, and extracellular histones levels were measured in two cohorts of patients with TLS. We developed a model of TLS in syngeneic mice with acute myeloid leukemia, and analyzed ultrastructural changes in kidneys and endothelial permeability using intravital confocal microscopy. In parallel, we studied the endothelial toxicity of extracellular histones in vitro. RESULTS: The study provides the first evidence that previously described crystal-dependent mechanisms are insufficient to explain TLS-induced AKI. Extracellular histones that are released in huge amounts during TLS caused profound endothelial alterations in the mouse model. The mechanisms of histone-mediated damage implicates endothelial cell activation mediated by Toll-like receptor 4. Heparin inhibits extracellular histones and mitigates endothelial dysfunction during TLS.ConclusionThis study sheds new light on the pathophysiology of TLS-induced AKI and suggests that extracellular histones may constitute a novel target for therapeutic intervention in TLS when endothelial dysfunction occurs.
Project description:Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly non-Hodgkin's lymphoma and acute leukemia due to chemotherapy or spontaneously. It is characterized by a biochemical abnormality such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and its clinical outcome is directly related to these biochemical abnormalities. Prevention and treatment of tumor lysis syndrome depend on immediate recognition of patients at risk. Therefore, identifying patients at risk and prophylactic measures are important to minimize the clinical consequences of tumor lysis syndrome. Patients with low risk should receive hydration and allopurinol. On the other hand patients with high risk should receive hydration and rasburicase in an inpatient setting. It is important to start therapy immediately, to correct all parameters before cancer treatment, to assess risk level of patients for TLS, and to select treatment options based on the risk level. In this review a comprehensive search of literatures was performed using MEDLINE/PubMed, Hinari, the Cochrane library, and Google Scholar to summarize diagnostic criteria, incidence, predicting factors, prevention, and treatment options for tumor lysis syndrome in patients with hematological malignancies.
Project description:Tumor lysis syndrome (TLS) is a metabolic disorder caused by massive tumor lysis. Hypouricemic agents are administered to prevent TLS-related hyperuricemia and renal failure. We experienced three cases of urine xanthine crystals during TLS in patients with hematologic malignancies who received prophylactic febuxostat. Yellowish and pinkish deposits were observed in urinary tract catheters and urinary bags. Urine microscopy revealed that the deposits were xanthine crystals. In rapid tumor lysis, inhibition of xanthine oxidase can cause xanthine accumulation and urine xanthine crystallization. During TLS, urine xanthine crystals may be overlooked, so careful observation and management are required to avoid xanthine nephropathy.
Project description:IntroductionTumor lysis syndrome (TLS) is an oncologic emergency characterized by several metabolic derangements, such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. TLS is typically observed in hematologic malignancies, especially after starting the first administration of antineoplastic therapies. TLS in a solid malignancy is very unusual, and exceedingly rare when occurring spontaneously, in the absence of chemotherapy.Case presentationWe report a case of a 76-year-old man with lung adenocarcinoma, which started as a cancer with indolent behavior and small tumor burden but relapsed in 5 months with rapidly proliferating metastatic disease. Spontaneous TLS was the presenting clinical manifestation of the tumor relapse, and it led to the patient's death.ConclusionTo our knowledge, this is the first case of spontaneous TLS in a relapsed adenocarcinoma of the lung reported in the medical literature. The development of the metabolic derangements of TLS should prompt the consideration of tumor relapse during the follow-up of patients with solid malignancies.
Project description:Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 109/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
Project description:Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B-cell lymphoma-2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control.Implications for practiceTumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.
Project description:Tumor lysis syndrome (TLS) is the rapid disintegration of a malignant tumor treated with anticancer drugs or radiation, causing electrolyte abnormalities such as elevated uric acid levels, elevated potassium and phosphorus levels, and decreased calcium levels. These abnormalities can lead to hypotension, renal dysfunction, consciousness disorders, and even death in some cases. The current patient was a 65-year-old woman who had breast cancer with local invasion, lung metastasis, and bone metastasis from the time of the initial disease onset. Despite the administration of various chemotherapy and hormone therapy regimens, the tumor increased gradually, and at 2 years and 5 months after the initial onset, pain and bleeding from metastatic infiltration of the cervical lymph nodes were noted. Therefore, radiotherapy was indicated for palliation of pain and bleeding caused by metastatic invasion of the cervical lymph nodes. Irradiation (30 Gy/10fr) was planned with a 3-field technique using 4MVX and 10MVX. Approximately 11 h after the initial irradiation, symptoms such as respiratory distress, tachycardia, and hypotension were observed. Blood tests revealed hyperuricemia and hyperkalemia, leading to a diagnosis of TLS. Dialysis and electrolyte correction were immediately initiated resulting in normalization of electrolytes and stabilization of the blood pressure. It is crucial to understand that TLS is relatively rare but can occur after radiation therapy or in solid tumors, and warrants a prompt response if suspected based on symptoms or blood findings.
Project description:BackgroundTumor lysis syndrome is an oncologic emergency that classically occurs following cancer therapy, although spontaneous tumor lysis syndrome can also occur in malignancies, albeit rarely. Spontaneous tumor lysis syndrome has previously been reported in some hematologic malignancies, but it rarely happens in solid tumors and seems to be associated with a higher mortality rate. This is the first case of adrenal adenocarcinoma that developed spontaneous tumor lysis syndrome.Case presentationWe present a rare case of spontaneous tumor lysis syndrome occurring in a patient previously diagnosed with adrenal adenocarcinoma. The patient was a 64-year-old Persian man with abdominal pain, hypersomnia, and fatigue who was previously diagnosed with right adrenocortical carcinoma and had undergone right adrenalectomy with regional lymph nodes resection 5 months previously. On physical examination, the patient had abdominal distension and mild tenderness at the right upper quadrant. Pitting edema was detected bilaterally in the lower extremities. Initial imaging revealed multiple and large lesions suggestive of liver metastases. The laboratory data showed hyperkalemia, hyperuricemia, hyperphosphatemia, and elevated serum creatinine level indicative of spontaneous tumor lysis syndrome in the patient. Despite immediate and intensive care with antibiotics, hydration, treatment with a hypouricemic agent, and renal replacement therapy, the patient ultimately died from multiorgan failure.ConclusionsTumor lysis syndrome in solid tumors has high mortality. Patients susceptible to spontaneous tumor lysis syndrome must receive aggressive treatment immediately, which is crucial for preventing morbidity and mortality. Spontaneous tumor lysis syndrome may be underdiagnosed, and a high degree of clinical suspicion is needed to make the diagnosis and proceed with required interventions. Therefore, clinicians should be aware of this rare phenomenon.