BACKGROUND Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) is associated with poor outcomes. However, the clinical features and risk factors of EHM of HCC after radiofrequency ablation (RFA) remain unclear. AIM To elucidate the characteristics and risk factors of EHM after RFA for HCC. METHODS From January 2008 to December 2017, we retrospectively enrolled 661 patients who underwent RFA as first-line treatment for HCC at 2 tertiary hospitals. The inclusion criteria were age ≥ 18 years, a diagnosis of HCC, and treatment-naivety. Abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and alpha-fetoprotein measurements were routinely performed at 1 mo after RFA and followed-up at intervals of 3-6 mo. Univariate analyses were performed using the chi-squared test or Student’s t -test, and univariate and multivariate analyses were performed via logistic regression, as appropriate. RESULTS EHM was diagnosed in 44 patients (6.7%) during a median follow-up period of 1204 days. The 10-year cumulative rate of HCC recurrence and EHM was 92.7% and 33.7%, respectively. Initial recurrence was most often intrahepatic, and the rate of extrahepatic recurrence at initial recurrence was only 1.2%. The median time to the diagnosis of EHM was 2.68 years, and 68.2% of patients developed EHM within 2 years of the first recurrence, regardless of recurrence-free survival and 75.0% of patients developed EHM within 5 years after first recurrence. EHM was mostly diagnosed via abdominal CT/MRI in 33 (75.0%) and 38 of 44 patients (86.4%) with EHM had either positive abdominal CT scan results or serum AFP level elevation. In multivariate analysis, recurrence-free survival < 2 years, ablation zone/tumor size < 2, and alpha-fetoprotein level > 400 IU/mL were associated with a high EHM risk. CONCLUSION EHM occurs following multiple intrahepatic recurrences after RFA and combined contrast-enhanced abdominal CT and serum AFP were useful for surveillance. Patients especially with high-risk factors require close follow-up for EHM.

We report a case of thromboembolism in a patient with hypernatremia resulting from lithiuminduced nephrogenic diabetes insipidus (NDI). A 49-year-old female patient on chronic lithium therapy due to bipolar disorder was transferred to the emergency department with signs of dehydration, altered mental status, and increased oxygen demand. She was admitted to a local psychiatric clinic first because of an exacerbation of a manic episode. When she was transferred to our clinic, her blood pressure was 130/80 mmHg, she was tachycardic (110 beats/min), had tachypnea (24 breaths/min), normal body temperature (36.5 ℃), and an oxygen saturation of 94% via a face mask (10 L/min). Laboratory results showed hypertonic hypernatremia (osmolality, 363 mOsm/kg; sodium, 171 mEq/L), low urine osmolality (osmolality, 231 mOsm/kg), and normal urine sodium (Na, 63 mEq/L). Her serum lithium concentration was above the therapeutic range (1.52 mmol/L). An increase in cardiac markers and changes in electrocardiogram were detected; therefore, echocardiography was performed, which showed right ventricular dysfunction and small left ventricular chamber size. Computed tomography of the chest and lower extremities showed pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT). She was treated with hypotonic fluid to correct hypernatremia and intravenous heparin for thromboembolism. The size of the thromboembolism decreased, and hypernatremia was corrected. She was discharged with a direct oral anticoagulant (DOAC). Here, we report a case of severe hypernatremia and venous thromboembolism in lithium-induced NDI.