Hepatic hemangioma
Hepatic hemangioma is the most common primary benign liver tumor, with a prevalence of 2.5–3.3%.11–13 Hemangiomas are usually small (<4 cm) and solitary, but clinicians occasionally encounter patients with hemangiomas measuring 10–20 cm in diameter, with most patients being asymptomatic.14 The following indications are usually applied to choose the treatment of hemangioma: (1) presence of persistent symptoms such as abdominal pain/discomfort and dyspepsia because of disturbance of bowel movements by mass effects related to hemangioma that are difficult to manage with medical treatments or (2) progressive enlargement of 1–2 cm per year even in asymptomatic patients.
Before treatment, the location of hemangiomas needs to be carefully examined to determine whether they are eligible for approach with an ablation needle (RFA electrode or MWA antenna) with an adequate sonographic window. A laparoscopic approach may be preferred in cases in which the percutaneous approach is difficult. Ultrasound (US) is the most frequently used tool for guiding ablation needles. Computed tomography (CT) guidance is used when US guidance is insufficient to support needle visualization and advancement. According to recent studies, either the laparoscopic/surgical or percutaneous approach is predominantly used with US guidance (Tables 2 and 3).15–29 Complete ablation was reported in >86% of patients with RFA and >84.6% with MWA. The resolution of clinical symptoms was achieved by most patients, complete resolution of clinical symptoms in 50–90.9% by RFA, and 50–100% by MWA.15–24 There are some possible complications of ablation for hemangioma, most of which are classified as Clavien-Dindo grade 1, with hemoglobinuria, fever, and pain being common events (Tables 4 and 5). 15–23,25–29 According to Wu et al.,25 the rates of achieving complete ablation and procedure-related complications were similar in 253 patients with hemangiomas of 5–9.9 cm and 38 patients with hemangiomas of ≥10 cm.25 However, the rates of hemolysis-related and systemic inflammatory response syndrome-related complications were higher in patients with hemangiomas of ≥10 cm than in those with hemangiomas of 5–9.9 cm. In addition, the postoperative stay was longer in the former than in the latter (9.04 vs. 5.73 days, p<0.001). The data suggest that care should be taken when performing ablation for hemangiomas of ≥10 cm in terms of safety risk and patient burden.
Table 2Effectiveness of RFA for hemangioma
N | Size in mm | US/CT | Approach | Effectiveness
| Reference |
---|
Symptom-related | Tumor reduction-related |
---|
44 (50) | 50–100 | US | Laparoscopy/Percutaneous | – | 86% with complete effect* | 16 |
4 | 106–145 | US | Surgical | 50% with complete relief | 58–92% volume reduction | 17 |
12 (15) | 25–95 | US | Percutaneous | 58.3% with significant/complete relief | 38–79% (mean, 67%) volume reduction | 15 |
291 (304) | 50–200 | US/CT | Laparoscopy/Percutaneous | – | 99% with complete effect* | 25 |
27 | 28–100 | US | Laparoscopy | 52% with complete relief | 100% with complete effect* | 20 |
24 (25) | 40–150 | US | Percutaneous | 71.4% with complete relief | 92% with complete effect* | 19 |
2 | 15.7–25 | US | Laparoscopy | 50% with complete relief | 56% and 32% reduction | 18 |
106** | 5–12.8 | US | Percutaneous | 90.9%/65%† with complete relief | 86.5%/40.7%†† with complete effect | 26 |
66# | 40–100 | US | Laparoscopy | 76.5% with complete relief | 94.4% with complete effect* | 28 |
72 | ≤50, <100 | US/CT | Laparoscopy/Percutaneous | – | 94.4% with complete effect | 29 |
Table 3Effectiveness of MWA for hemangioma
N | Size in mm | US/CT | Approach | Effectiveness
| Reference |
---|
Symptom-related | Tumor reduction-related |
---|
46 (47) | 50–96 | US | Percutaneous | – | 91.5% with complete effect* | 21 |
44 | 106–145 | US | Percutaneous | 50% with complete relief | 93.2% with complete effect* | 22 |
82 | 50–100 | US | Percutaneous | 88.6% with complete relief | 89.0% with complete effect* | 27 |
12 (13) | 100–145 | US | Percutaneous | 100% with complete relief | 84.6% with complete effect* | 23 |
40 (42) | 41–108 | US | Percutaneous | 95% with clinical effectiveness† | 100% with technical effectiveness# | 24 |
72 | ≤50, <100 | US/CT | Laparoscopy/Percutaneous | – | 95.8% with complete effect* | 29 |
Table 4Complications related to RFA for hemangioma
N | Size in mm | Complications | | Reference |
---|
44 | 50–100 | Clavien-Dindo Grade 1* | | 16 |
| | Hemoglobinuria | 18.2% | |
| | Hemolytic jaundice anemia | 11.3% | |
| | Elevated serum transaminase | 11.3% | |
| | Fever | 9.1% | |
| | Skin burns | 9.1% | |
| | Transient renal damage | 6.9% | |
| | Hydrothorax | 6.9% | |
| | Clavien-Dindo Grade 3a* | | |
| | Pneumothorax | 2.3% | |
| | Liver abscess | 2.3% | |
4 | 106–145 | Self-limiting postprocedural pain lasting for 6 days | 25% | 17 |
| | Macroscopic hematuria lasting for 24 h | 25% | |
12 | 25–95 | NONE | | 15 |
291 | 50–200 | Clavien-Dindo Grade 1 | | 25 |
| | Hemoglobinuria | 81.9% | |
| | Anemia | 13.2% | |
| | Lung injury | 1.6% | |
| | SIRS | 39.1% | |
| | Postprocedural pain | 7.2% | |
| | Transient hepatic injury | 16.1% | |
| | Asymptomatic pleural effusion | 5.9% | |
| | Skin burn | 1% | |
| | Clavien-Dindo Grade 2 | | |
| | Esophageal injury | 0.3% | |
| | Myocardial dysfunction | 0.3% | |
| | Clavien-Dindo Grade 2–3 | | |
| | Diaphragmatic injury | 1.3% | |
| | AKI | 1% | |
| | Clavien-Dindo Grade 3 | | |
| | Symptomatic pleural effusion | 0.3% | |
| | Bleeding at the electrode entry site | 1.3% | |
| | Rupture of hepatic hemangioma | 1% | |
| | Clavien-Dindo Grade 4 | | |
| | ARDS | 0.3% | |
27 | 28–100 | Postoperative low-grade fever | 48.1%** | 20 |
| | Elevated serum transaminase | 48.1%** | |
24 | 40–150 | Abdominal pain | 16.7%*** | 19 |
| | Fever | 8.3%*** | |
| | Anemia | 8.3%*** | |
| | Jaundice | 12.5%*** | |
| | Ascites | 4.2%*** | |
2 | 15.7–25 | AKI, anemia | 100% | 18 |
106 | 5–12.8 | Clavien-Dindo Grade 1 | | 26 |
| | Pleural effusion | 7.5% | |
| | Clavien-Dindo Grade 2 | | |
| | Fever | 8.5% | |
| | Hemoglobinuria | 2.8% | |
| | Moderate anemia | 1.9% | |
| | Acute renal insufficiency | 2.8% | |
| | Jaundice | 16% | |
| | Clavien-Dindo Grade 3 | | |
| | Abdominal Hemorrhage | 0.9% | |
66# | 40–100 | Fever | 18.8% | 28 |
| | Hemoglobinuria | 3.1% | |
| | Transient renal damage | 3.1% | |
| | Jaundice | 3.1% | |
144## | | Clavien-Dindo Grade 1 | | 29 |
| | Hemoglobinuria | 76.4% | |
| | SIRS | 30.6% | |
| | Hemolytic jaundice | 8.3% | |
| | Anemia | 6.9% | |
| | Postprocedural pain | 8.3% | |
| | Transient hepatic injury | 12.5% | |
| | Asymptomatic pleural effusion | 2.8% | |
Table 5Complications related to MWA for hemangioma
N | Size in mm | Complications | | | Reference |
---|
46 (47) | 50–96 | Minor complications (fever, mild pain and transient hepatic dysfunction)* | 78.3% | | 21 |
| | Major complications (2 with acute renal dysfunction** , 2 with symptomatic pleural effusion**, and 1 with Hyperbilirubinemia) | 10.9% | | |
44 | 106–145 | Clavien-Dindo Grade 1 | | | 22 |
| | Pain | 22.7% | | |
| | Excessive wound exudate | 6.8% | | |
| | Low-grade fever | 4.5% | | |
| | Coprostasis | 13.6% | | |
| | Stomach discomfort | 4.5% | | |
| | AKI | 6.8% | | |
| | Clavien-Dindo Grade 3 | | | |
| | Diaphragmatic hernia | 2.3% | | |
82 | 50–100 | Major complications | 9.8% | SIR# | 27 |
| | Diaphragmatic hernia | 1.2% | D | |
| | Symptomatic pleural effusion | 2.4% | C | |
| | Jaundice | 2.4% | C | |
| | Acute renal dysfunction | 3.7% | C | |
| | Minor complications | 43.9% | | |
| | Fever | 6.1% | B | |
| | Abdominal pain | 22% | B | |
| | Both fever and pain | 6.1% | B | |
| | Other discomfort | 9.8% | A | |
12 (13) | 100–145 | Fever (≧38) | 15.4% | | 23 |
| | Constipation | 30.8% | | |
| | Slight wound pain | 30.8% | | |
| | Stomach discomfort | 7.7% | | |
| | High bilirubin (total bilirubin >34.2 mmol/L) | 53.8% | | |
| | Anemia (hemoglobin <100 g/L) | 30.8% | | |
| | Elevated serum transaminase (>80 U/L) | 100% | | |
| | Elevated serum creatinine | 15.4% | | |
40 (42) | 41–108 | Fever (37.2–8.5 Celsius degrees lasting 1–2 days) | 15% | | |
| | Pleura effusion without drainage | 5% | | |
| | Hemoglobinuria at the first urination after ablation | 37.5% | | |
| | AKI caused by massive heat-induced intravascular hemolysis## | 2.5% | | |
144§ | | Clavien-Dindo Grade 1 | | | 29 |
| | Hemoglobinuria | 48.6% | | |
| | SIRS | 15.3% | | |
| | Hemolytic jaundice | 2.8% | | |
| | Anemia | 4.2% | | |
| | Postprocedural pain | 4.2% | | |
| | Transient hepatic injury | 4.2% | | |
| | Asymptomatic pleural effusion | 1.4% | | |
Regarding technical aspects, Qu et al.26 recommended the use of three-step RFA for hepatic hemangiomas of 5–12.8 cm, briefly defined by the ablation of the target lesion following ablation of the feeding artery and aspiration of blood from the tumor. The technique appears to increase the efficiency of RFA, with a shorter ablation time, fewer punctures, improved effectiveness and safety, better complete ablation rate, better maximum postoperative pain score, better symptomatic relief, and lower rate of severe complication. In addition, as they reported a shorter hospital stay, three-step RFA may benefit patients by reducing the burden, but there was no description of the financial aspect.
According to the study comparing MWA (n=82, 6.9±1.8 cm) and transcatheter arterial embolization (TAE; n=53, 7.1±1.5 cm) for the treatment of large hepatic hemangiomas,27 the MWA group had a significantly higher rate of complete radiological response defined as no obvious enhancement of lesions on contrast-enhanced CT/magnetic resonance imaging (MRI; 89.0% vs. 37.7%, p<0.001) and complete clinical response defined as disappearance of hemangioma-related symptoms (88.6% vs. 69.2%, p=0.046). MWA was associated with fewer minor complications, defined as events without substantial morbidity or disability that increased the level of care (43.9% vs. 66.0%, p=0.019), shorter time of analgesic use (p<0.001), and shorter hospital stay (p=0.003) than the TAE group. The study suggests that TAE has limited effectiveness for volume reduction of hemangioma. Meanwhile, Wang et al.30 reported the outcome of TAE followed by percutaneous US-guided MWA for hemangioma (95 × 97 × 117 mm), with an 80% reduction with no complications, which might have potential as an option for the treatment of large hemangioma. A recent prospective study compared the clinical results of laparoscopic RFA (6.4 cm, 4.0–9.3) and open resection (6.5 cm, 4.0–9.8) for the treatment of symptomatic-enlarging hepatic hemangiomas.28 Although radiological and clinical responses were comparable between the groups, the laparoscopic RFA group had a significantly shorter operative time and less blood loss than the open resection group. In addition, patients who underwent laparoscopic RFA experienced significantly less pain, required less analgesia, had a significantly shorter length of hospital stay, and had lower hospital costs compared with those who underwent open resection. Another study retrospectively compared the effectiveness of percutaneous MWA and surgical resection (open 62 and laparoscopic 6) for hemangiomas (6.3±1.4 cm, 5.0–9.6); the MWA group had a significantly shorter operative time, less blood loss, and a lower rate of prophylactic abdominal drainage than the surgical resection group.22 In addition, postoperative recovery was significantly better and duration of hospital stay was significantly shorter in the MWA group than in the surgical resection group. However, there was no significant difference in effectiveness between the groups. Taken together, despite the limited number of studies comparing ablation and surgical treatment, ablation appears to provide an sufficient therapeutic effect compared with open surgery, with the advantages of safety and less burden for patients. However, difference of clinical effectiveness between RFA and MWA for hemangioma has not been fully described, as limited studies have compared the two methods. In a recent study, MWA had a shorter ablation time, fewer hemolysis-related complications, and a shorter hospital stay.29 Additional studies may be required to compare RFA and MWA, and long-term outcomes of ablation for hemangioma with cost effectiveness.
Hepatocellular adenoma (HCA)
HCA is a benign liver tumor that most often develops in young women taking oral contraceptives, with an incidence of approximately 3 per 100,000 women.31 Complications such as hemorrhage (15–20%) or malignant transformation (5%) appear to increase with increase in tumor size. Therefore, surgical treatment is recommended for HCAs of >5 cm.32
There are limited reports regarding the ablative effects of HCA (Table 6).33–37 Rocourt et al.33 reported a 13-year-old patient in whom a liver tumor measuring 35 mm was incidentally detected and was histologically diagnosed as adenoma by percutaneous biopsy.33 Because of the relatively small lesion, RFA was selected as the treatment of choice. US-guided percutaneous RFA was performed under general anesthesia with three sequential overlapping ablations of 12 min each. No evidence of recurrence was seen on MRI 2 years after treatment. A study of three cases of multiple HCAs (2–5 cm) treated with hepatic resection combined with RFA (intraoperative approach with no complications) was reported in the USA in the same year.34 An RFA study by McDaniel et al.35 used four cool-tip 15 cm long electrodes (Radionics, Burlington, MA, USA) and a 3 cm ablative zone, under laparoscopic US guidance with a four-way laparoscopic 8666-RF intraoperative transducer (BK Medical, Peabody, MA, USA) to treat HCA (segment 7; 5.5 cm) adjacent to the right hemidiaphragm in an 11-year-old patient with chronic liver disease secondary to alpha-1-antitrypsin deficiency. The patient did well after treatment and was discharged on the third post-operative day. The follow-up MRI performed 19 months after the first RFA procedure showed a further decrease in the ablation zone size, with no residual tumor. Costa et al.36 treated 16 patients with 26 HCAs between 11 and 48 mm with US/CT-guided RFA using coaxial 14–18 gauge RFA needles and 3–4 cm cool-tip needle systems.36 The treatment was uneventful and technically successful in all cases. Only one patient (4%) had residual lesions that increased in size over time, but showed no further enlargement in or around the ablated area after re-ablation. The mean follow-up was 27 (range: 2–84) months. The authors also found that fat in the ablation zone of HCAs was a common finding on MRI, which, in isolation, does not indicate residual tumors. Thus, RFA seems to have beneficial effects in the treatment of HCAs, meanwhile, there is a case report that demonstrated the effect of percutaneous CT-guided irreversible electroporation, a nonthermal ablation of a 5 cm HCA in a 28-year-old woman who wanted to get pregnant.37 It was effective, with rapid and impressive tumor shrinkage without any complications. However, it should be noted that HCAs are benign tumors, and treatment is limited to preventing bleeding or malignant transformation. Radical treatment needs to be selected according to the subtype, as described in recently published guidelines endorsing the use of personalized clinical care.38 Following the guidelines, the indications for treatment are any HCA in men regardless of size and subtype and HCAs of >5 cm or much rarer smaller HCAs with worrisome features such as β-catenin activation or rapid growth in women.38 Appropriate selection of surgical or nonsurgical treatment including various ablation techniques, should be further investigated in studies with large patient populations.
Table 6Ablation for hepatocellular adenoma
N | Size in mm | Method | Guidance | Approach | Effect | Reference |
---|
1 | 55 | RFA | US | Laparoscopy | No residual tumor, 19 months | 35 |
1 | 35 | RFA | US | Percutaneous | No recurrence, 2 years | 33 |
3 (*) | 20–50 | RFA | US | Surgical | 1 residual tumor** | 34 |
16 (26) | 11–48 | RFA | US/CT | Percutaneous | 1/26 (4%) with residual tumor** | 36 |
1 | 50 | IRE | CT | Percutaneous | Rapid tumor shrinkage | 37 |