Tumor Lysis Syndrome

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Tumor Lysis Syndrome

Introduction

• Tumor lysis syndrome is a life-threatening metabolic emergency that occurs when cancer cells are rapidly destroyed, releasing their contents into the bloodstream. This can happen spontaneously or as a result of chemotherapy, radiation therapy, or surgery. 
• Tumor lysis syndrome is characterized by a constellation of metabolic abnormalities, including hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, azotemia, and oliguria. 
• If left untreated, Tumor lysis syndrome can lead to cardiac arrhythmias, seizures, renal failure, and death. The Table on the left shows laboratory findings that are commonly used to diagnose tumor lysis syndrome.

Causes of Tumor Lysis Syndrome

• The most common types of cancer that can cause Tumor lysis syndrome are: Leukemia, Lymphoma, Burkitt's lymphoma, Acute myeloid leukemia, Small cell lung cancer, Breast cancer, Ovarian cancer, and Testicular cancer.
• Tumor lysis syndrome is more likely to occur in patients with: High tumor burden, Rapidly growing tumors, Tumors that are sensitive to chemotherapy or radiation therapy, and Pre-existing renal dysfunction. The Table on the left is a list of risk factors associated with Tumor lysis syndrome.

Pathophysiology

• The pathophysiology of Tumor lysis syndrome is complex and involves a cascade of events that are triggered by the release of cellular contents from rapidly lysed cancer cells. 
• These cellular contents include potassium, phosphate, uric acid, and other metabolites. The accumulation of these metabolites, if left untreated, can lead to cardiac arrhythmias, seizures, renal failure, and death.

Hyperkalemia.

• The release of potassium from lysed cancer cells can lead to hyperkalemia, which can cause cardiac arrhythmias and sudden death.

Hyperphosphatemia.

• The release of phosphate from lysed cancer cells can lead to hyperphosphatemia, which can precipitate as calcium phosphate crystals in the kidneys, causing acute kidney injury, renal failure, and hypocalcemia.

Hypocalcemia.

• Hypocalcemia can occur as a result of hyperphosphatemia, which binds to calcium and forms insoluble calcium phosphate complexes. Hypocalcemia can cause neuromuscular irritability and seizures.

Hyperuricemia.

• The release of uric acid from lysed cancer cells can lead to hyperuricemia, which can cause uric acid crystallization in the kidneys and renal failure.

Azotemia.

• Azotemia is the accumulation of nitrogenous waste products in the blood, such as urea and creatinine. Azotemia and oliguria can occur as a result of renal failure.

Clinical Manifestations

• The clinical manifestations of Tumor lysis syndrome can vary depending on the severity of the condition. However, some of the most common symptoms include: Nausea, Vomiting, Diarrhea, Abdominal pain, Muscle weakness, Seizures, Coma, Cardiac arrhythmias, and Renal failure.

Diagnosis

• Tumor lysis syndrome is diagnosed based on a combination of clinical symptoms and laboratory findings. 
• The following laboratory tests are typically used to diagnose Tumor lysis syndrome: Serum potassium, Serum phosphate, Serum calcium, Serum uric acid, Blood urea nitrogen, and serum Creatinine. The Cairo-Bishop criteria defines Tumor lysis syndrome as the presence of at least two metabolic disturbances within 3 days before or 7 days after initiation of therapy. 

Treatment

• The treatment of Tumor lysis syndrome is aimed at correcting the metabolic abnormalities and preventing complications. The following treatments are typically used:
• Intravenous fluids to correct dehydration and electrolyte imbalances.
• Allopurinol works by inhibiting xanthine oxidase, the enzyme responsible for converting hypoxanthine to uric acid.
• Rasburicase is a recombinant version of the enzyme urate oxidase, which enhances the conversion of uric acid to a soluble metabolite, allantoin.
• Both Allopurinol and Rasburicase are effective in lowering serum uric acid level.
• Sodium bicarbonate to alkalinize the urine and prevent uric acid crystallization.
• Dialysis to remove waste products from the blood.
• It is generally not recommended to supply calcium to these patients, as this can increase the calcium phosphate product and lead to further renal deposition and damage. 

Prevention

• The best way to prevent Tumor lysis syndrome is to identify patients at risk and start treatment before the condition develops. Patients at risk for Tumor lysis syndrome should be given prophylactic treatment with allopurinol or rasburicase before starting chemotherapy or radiation therapy. It is also advisable to avoid substances that can potentially cause vasoconstriction of the renal vasculature, such as NSAIDs and iodinated contrast.

Conclusion

• Tumor lysis syndrome is the most common oncologic emergency. This condition is prevalent in both adult and pediatric oncology patients undergoing chemotherapy, though it can also occur spontaneously.
  
• Most of the symptoms seen in patients with tumor lysis syndrome are related to the release of intracellular chemical substances that cause impairment in the functions of target organs. 

• The accumulation of these metabolites, if left untreated, can lead to cardiac arrhythmias, seizures, renal failure, and death.