RF Ablation of Giant Hemangiomas Inducing Acute Renal Failure: A Report of Two Cases
In patients that require treatment for hepatic giant cavernous hemangiomas (GCH), radiofrequency ablation (RFA) has been suggested to represent a safe and effective alternative to invasive surgery. In a recent report of bipolar RFA, using two expandable needle electrodes, was uneventfully performed in patients with large GCH (>10 cm). The objective of this report is to present two cases in which bipolar RFA of symptomatic GCH was complicated by acute kidney injury.
Materials and methods
In 2015 we treated two patients for very large symptomatic GCH (15.7 and 25.0 cm) with bipolar RFA during open laparotomy.
In both patients the urine showed a red–brown discoloration directly after the ablation. They became anuric and presented with progressive dyspnea, tachypnea, and tachycardia, requiring hemodialysis for a period of 1 month in one case. Lab results revealed hemepigment-induced acute kidney. Both patients fully recovered and both showed a complete relief of symptoms at 3 months following the procedure.
RFA for large GCHs can cause hemepigment-induced acute kidney injury due to massive intravascular hemolysis. The presented cases suggest that caution is warranted and advocate an upper limit regarding the volume of GCHs that can be safely ablated.
KeywordsRadiofrequency ablation Giant cavernous hemangioma Hemolysis Acute kidney injury
Hepatic hemangioma is the most frequently encountered solid benign liver tumor. Lesions greater than 5 cm have been referred to as giant cavernous hemangiomas (GCH) . Although most hemangiomas are asymptomatic and are managed safely with observation alone, larger lesions may produce a variety of symptoms and signs, including pain, fullness, nausea, vomiting, and fever. For patients with invalidating symptoms the most renowned treatment remains surgical resection. Unfortunately, surgical resection is associated with morbidity up to 27 % and even a small risk of mortality [2, 3, 4]. Although mainly based on small case series and case reports, radiofrequency ablation (RFA) has shown promising results in the recent literature for the less-invasive treatment of relatively small GCH with only minor complications documented [5, 6, 7, 8, 9, 10, 11, 12, 13]. In a recent report four patients with symptomatic GCHs measuring >10 cm were uneventfully treated with bipolar RFA . A remarkable volume reduction (58–92 %) coincided with complete (2/4 patients) or considerable (2/4 patients) symptom relief. This case report describes two patients with very large symptomatic GCHs who developed acute kidney injury (AKI) shortly after bipolar RFA, caused by massive heat-induced intravascular hemolysis.
Materials and methods
In the following cases a commercially available generator (RF3000, Boston Scientific, USA) was combined with two expandable 7 cm bipolar needle electrodes (InCircle, RF Medical, USA). The procedures were performed using intraoperative ultrasound during open laparotomy under general anesthesia. Ablation protocol was similar to the previously described technique .
The local review board waived approval since (1) both the generator and needle electrodes have a CE mark for the ablation of liver tumors, (2) we have a well-documented and transparent prospective registry for all ablations, including our previous experience with RFA for symptomatic GCH, and (3) the multidisciplinary tumor board unanimously agreed on the indication. Patients gave written informed consent and all procedures were conducted according to the guidelines for good clinical practice. Follow-up at 3 months was performed by a contrast-enhanced CT or MRI scan with intravenous contrast. Volume reduction was calculated in percentages and symptom relief was objectified by a visual analogue scale (VAS score).
Hemepigment-induced AKI can either develop from rhabdomyolysis or intravascular hemolysis. The latter is rare and is caused by for example paroxysmal nocturnal hemoglobinuria and G6PD deficiency [15, 16]. The nearly unavoidable hemolysis after RFA, attributable to the generous blood supply of GCHs, especially for those > 10 cm, is a major drawback. Massive hemolysis can lead to various degrees of hemoglobinuria, hemolytic jaundice, anemia, and renal damage . The development of AKI associated with hepatic RFA has been previously reported in the treatment of liver metastases and hepatocellular carcinoma [18, 19, 20, 21]. Also, acute hemolysis secondary to microwave-assisted liver resection and cryoablation has been described [22, 23]. AKI as a result of RFA-induced hemolysis for giant hemangiomas or other benign liver lesions has not been reported before. Our patients developed oliguria that progressed to acute renal failure. The most likely cause of renal failure was heme-induced nefropathy caused by thermal hemolysis. The postoperative decrease in hemoglobin with fragmentocytes, the unmeasurably low haptoglobin, the postprocedural positive hemoglobin urine dipstick-test plus the reddish-brown discolored urine all support this etiology.
During RFA, the temperature of the tissue adjacent to the radiofrequency probe reaches temperatures between 50 °C and 100 °C. Red blood cells (RBCs) will undergo budding and fragmentation when exposed to a temperature of >49 °C in vitro [24, 25]. The size of the giant hemangiomas, and hence the size of the ablation zone and length of the procedure, presumably resulted in a more massive thermal hemolysis than that encountered with smaller tumors and shorter procedures.
Hemoglobin is released upon erythrocyte destruction and is filtered by the glomerulus into the urinary space. In the urinary space, hemoglobin is degraded and releases hemepigments which are toxic to the kidney. Hemepigments can cause tubular injury by (1) tubular obstruction, (2) damage due to direct proximal tubular cell injury, and (3) vasoconstriction, resulting in reduced blood flow in the outer medulla . AKI that develops in the setting of hemolysis is rarely an isolated cause. Predisposing conditions, like volume depletion and, possibly, mild ischemia are often present. Volume depletion enhances both vasoconstriction and the formation of obstructing casts, and is of critical importance for the development of heme-induced AKI . Our patients did not experience renal hypoperfusion caused by prolonged hypotension or hypovolemia, and renal toxic drugs like NSAID’s or cephalosporins were not administered.
Laparoscopic insufflation can also contribute to intraoperative oliguria due to increased intraabdominal pressure which can lead to decreased renal perfusion and increased renin activity . In both patients the ablation was performed during open surgery, so no laparoscopic insufflation was used.
Although a percutaneous approach generally is less invasive, we preferred an open approach to avoid injury to adjacent organs, to facilitate a more aggressive ablation and to increase precision of needle advancement using intraoperative ultrasound. Moreover, the unusually large needle thickness for the ellipsoid-shaped trocar increases the risk of hemorrhage and bile duct trauma and, in its current form, seems unsuitable for percutaneous use.
In conclusion, we believe that the most likely cause of AKI in our two cases was hemolysis caused by extensive thermal ablation with a bipolar system. Laboratory monitoring after extensive or prolonged radiofrequency liver ablation procedures is recommended for early detection hemolysis. Laboratory values that should be monitored include hemoglobin, creatinine, fragmentocytes, haptoglobin, lactate dehydrogenase, CPK, and urinalysis. In addition, perioperative volume repletion should be warranted, especially if oliguria is noted and/or hemolysis is suspected. When treating large GCH with thermal ablation, the number of ablations and the duration of the ablation sequences should be reduced to the absolute minimum. For colossal tumors or multiple tumor sites a multistep approach or other treatment options should be considered to prevent hemepigment-induced AKI. The general acceptance of thermal ablation for symptomatic GCHs in routine clinical practice seems precipitated. Given the paucity of patients with an unresectable symptomatic GCH, it may prove difficult to setup larger safety studies. Outside the setting of clinical trials we recommend reticence, especially for GCHs >10 cm.
Compliance with Ethical Standard
Conflicts of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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