Among the methods used to treat ICC, surgery is unquestionably the optimum, and yields a 5-year survival rate of 17%-46%[4-7]
. However, only a small subset of patients can benefit from surgery and the recurrent rate is as high as 80%[6, 7]
. At the time of recurrence, the tumor is mostly multifocal or the patient has poor general condition or limited remnant liver. So management of patients with RICC following surgical resection is challenging. Reports of repeated hepatectomies due to RICC are rare[6, 8]
. At the same time, some researchers considered RICC as contraindication to curative surgical management[17,18]
. The prognosis for patients with unresectable ICC is extremely poor, with survival of 5-8 months[5-8]
Because surgical therapy is not indicated in majority of RICC cases, other treatment modalities should be considered. Unfortunately, the nonsurgical management failed to prolong patient’s survival or had only slightly increased survival. External radiotherapy (RT) with or without intraoperative radiotherapy and intraluminal radiotherapy (brachytherapy) has been explored in the adjuvant setting but showed no significant benefits after R0 resections[19-21]
. The unsuccessful results maybe related to this fact that ICC is mainly classified as adenocarcinoma, which is not sensitive to radiotherapy[1, 2]
Systemic chemotherapy for cholangiocarcinoma didn’t show significant survival benefits neither[22,23]
. Although chemotherapy has been reported to be more beneficial than the best supportive care
, systemic chemotherapy with a combination regimen (5-fluorouracil, doxorubicin, cisplatin, and mitomycin-C) is not entirely satisfactory in terms of survival outcomes. The range of median survival was only 6.5 to 11.5 months for patients treated with systemic chemotherapy[25,26]
. There is no randomized, prospective trial data in this disease, and standard chemotherapy regimen has not been established yet.
Compared with systemic chemotherapy, TACE or transcatheter arterial chemoinfusion (TACI) has the advantages of increasing the local concentration of chemotherapeutic agents to kill cancer cells without damaging healthy liver tissue and of reducing systemic side effects. It was reported the median survival of TACE for RICC was ranged from 9.0-17.3 months[27-29]
. Tumor vascularity is closely associated with treatment response[28,29]
. ICC with rich arterial supply more likely has tumor response to TACE than ICC with a decreased arterial supply. However, the problem is that most ICCs are of hypovascular[1,2]
. So the efficacy of TACE for treating inoperable cholangiocarcinoma in the majority of patients remains questionable.
Recent years, RFA which can produce localized tumor destruction by heating tumor tissue has shown some benefits in selected groups of RICC patients by several case series[17, 30, 31]
. Kim, et al. firstly reported the role of percutaneous RFA in RICC and evaluated survival results in 20 patients with 29 RICC in 2010. In 20 patients with 29 RICCs, the technical effectiveness rate of RFA was 97% (28/29), median overall survival after RFA was 27.4 months, and the cumulative overall 1, 2, and 4 year survival rates were 70%, 60%, and 21%, respectively
. Our result is comparable to their study, the median overall survival was 30 months and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. One patient survived for 91 months and received RFA treatments four times. The advantage of RFA is that it can be repeated many times easily to treat residual tumor or intrahepatic recurrence. The studies above showed RFA was superior to other palliative therapies in prolonging patients’ survival in selected patients.
Chiou, et al. had reported a series of 10 ICC patients underwent RFA. They analyzed the correlation between RFA efficacy and tumor size. Based on 1 month CT, complete necrosis was seen in all of the five tumors (100%) with diameters of 3.0 cm or less, two of three tumors with diameters of 3.1-5.0 cm, and one of two tumors with diameters of more than 5.0 cm
. The results demonstrated that tumor size was a main risk factor for local tumor progression. However, in our study, with the individualized treatment strategies and adjunctive measures used[13, 14]
, the ablation success rate can be up to 94.7% for the tumors with the median size of 3.2 cm (range, 1.9-6.8 cm). In fact, as the improvement of RFA equipments, overlapping techniques and different approaches of RFA were developed, it has been reported RFA can effectively ablate intrahepatic tumors both metastatic and primary tumor with size up to 12 cm in diameter[17, 34]
In addition, open RFA was used in our study for 2 patients. It permits the ablation of liver tumors close to surrounding organs, such as bowel, kidney, gallbladder and diaphragm. The risk of injury will be high if these tumors are treated by percutaneous RFA. Also, percutaneous RFA is not fit for patients with serious intra-abdominal adhesions because adjuvant therapy such as artificial ascites usually failed. In fact, many researchers had proved open RFA can achieve a higher complete ablation rate and a lower local recurrence rate than percutaneous approach[34, 35]
One symptomatic pleural effusion was reported in our study. The patient was a female patient with a 3.0 cm tumor close to the diaphragm. Three days after open RFA, she developed pleural effusion and had symptoms of dyspnea. Two times of thoracentesis was performed and the patient relieved within two weeks. In fact, most pleural effusion after ablation was asymptomatic and usually resolved spontaneously. The incidence of symptomatic pleural effusion requiring thoracentesis was about 0.2% among hepatocellular carcinoma (HCC) patients
. It was common to find pleural effusion after ablation in patients with tumors located less than 2 cm from the diaphragm
. Only the patients with symptoms of dyspnea need further treatment, and in some patients, the pleural effusion was refractory, necessitating repeated aspiration
As a result of the low incidence of ICC and the initial use of RFA as a possible treatment option for RICC, our patient population is unfortunately small. The facts that our study is not randomized and lacks of control group are also limitations. However, our population size of 12 patients is comparable to those of other reports of palliative treatments for RICC and demonstrates the potential application of RFA in the management of RICC.
In conclusion, this preliminary clinical study showed minimally invasive RFA can effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery. Although our preliminary results are encouraging, well- designed controlled trials with a large sample are needed to further confirm the role of RFA in the treatment of postoperative recurrences of ICC.