Tumor Lysis Syndrome in Patients With Hepatocellular Carcinoma: A Systematic Review of Published Case Reports

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. It is characterized by massive tumor cell death leading to metabolic derangements and multiple organ failure. It is a rare complication of hepatocellular carcinoma (HCC) with only a few cases have been reported in the literature to date. We collected and summarized published case reports of tumor lysis syndrome in patients with HCC. We also reported one additional case who developed TLS after sorafenib therapy and wrote a clinical vignette. A comprehensive and current search for relevant articles was conducted in Medline and EMbase through May 2018. A systematic review was performed following the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).  A total of 28 cases of TLS associated with HCC were enrolled in our review. The median age of included cases was 55.5 years with a male to female ratio of 25:3. The two most common attributed factors of TLS were transcatheter arterial chemoembolization (TACE) (12 cases, 42.9 %) and sorafenib (nine cases, 32.1%). Among enrolled cases, the diameter of the largest tumor was 12 cm. Regarding Barcelona Clinic Liver Cancer (BCLC) staging, seven cases were at least stage A (22.6%), 11 cases were at least stage B (35.5%), and 10 cases were at least stage C (32.3%). The median time of onset of TLS was three days. As for uric acid-lowering agents, nine cases (32.1%) used allopurinol and four cases (14.3%) used rasburicase. Ten cases (35.7%) did not specify the medication prescribed. The overall mortality rate of this cohort was 67.9%. Compared with patients developing TLS following TACE, patients who had TLS following sorafenib therapy had a later onset of TLS (two days versus seven days, p < 0.001) and a more advanced stage of HCC (p = 0.002). There was a trend toward increased mortality of patients in the sorafenib group in comparison with those in the TACE group (77.8% versus 41.7%, p = 0.18). The results of this current review suggest that TLS rarely occurs in HCC but carries significantly higher mortality compared to TLS occurring in hematologic malignancies. It may occur shortly after TACE or with a delayed onset following sorafenib therapy. Considering the kaleidoscope of novel therapies and diverse pathogenesis of HCC, it is crucial for clinicians to recognize the clinicolaboratory derangements suggestive of TLS and initiate appropriate management. The present review highlights the need for clinicians to consider TLS within differentials when caring for patients with HCC.