Abstract
Background
As a minimally invasive treatment, ethanol sclerotherapy has been used for large symptomatic hepatic cysts, but there are not many long-term reports on treatment outcomes and safety.
Purpose
To evaluate the long-term outcomes of percutaneous ethanol sclerotherapy in patients with large symptomatic hepatic cysts.
Material and Methods
This study included 43 symptomatic, enlarging hepatic cysts in 42 patients who had undergone ethanol sclerotherapy from 2003 to 2013 and were followed up for >1 year. The treatment outcomes were evaluated in terms of the reduction of cyst size and resolution of symptoms. The patients were followed up for a mean period of 33 months with either ultrasound or computed tomography examination.
Results
Thirty-nine hepatic cysts (91%) were successfully treated with ethanol sclerotherapy, showing resolution of symptoms and remarkable reduction in cyst volume. Eight hepatic cysts (19%) disappeared completely, and 31 hepatic cysts (72%) decreased in size during the follow-up period. The mean diameter of the cysts decreased from 12.5 ± 4.4 cm to 3.8 ± 3.4 cm during follow-up. There were no immediate serious complications related to the procedure. There were four cases (9%) of treatment failure requiring subsequent surgical procedures.
Conclusion
Percutaneous ethanol sclerotherapy can be considered as an effective first-line treatment for large symptomatic hepatic cysts.
Introduction
Simple hepatic cysts are commonly encountered in clinical practice, with a prevalence ranging from 5% (detected with ultrasound [US]) to 18% (detected with computed tomography [CT]) in the general population (1,2). These cysts result from the abnormal congenital development of intrahepatic ducts, which are lined by a single layer of cuboidal epithelium (3). Most simple cysts are clinically benign and asymptomatic. Although enlarging hepatic cysts occur in a few patients, most are clinically insignificant because they grow very slowly during a period of years and do not require regular follow-up (1). However, in rare cases, hepatic cysts can cause symptoms such as pain, abdominal bloating, and early satiety, leading to the deterioration of the quality of life. The mass effects of large hepatic cysts can cause biliary tract compression, resulting in abnormal liver function tests. Other complications of hepatic cysts include infection, rupture, and hemorrhage into the cyst (1).
Although surgery has been the standard treatment for hepatic cysts for decades (3,4), it is an invasive modality that is not easily accepted as a treatment for a benign disease by patients or clinicians in the era of minimal invasive therapy (4). Since Bean and Rodan first reported aspiration and injection of alcohol as a treatment option in 1985 (5), several case series have reported the treatment outcomes of needle aspiration and ethanol sclerotherapy for hepatic cysts (2,6,7). However, there are limited data on the long-term treatment outcomes of ethanol sclerotherapy for large hepatic cysts in a large number of patients.
The aim of this study was to evaluate the long-term treatment outcomes and safety of percutaneous ethanol sclerotherapy as a minimally invasive treatment for large symptomatic hepatic cysts requiring surgical intervention.
Material and Methods
Patient selection and assessment
Patients with enlarging, symptomatic large hepatic cysts who were treated with ethanol sclerotherapy at the Kyungpook National University (Daegu, Republic of Korea) Hospital and the Kyungpook National University Medical Center between 2003 and 2013 were retrospectively reviewed. Patients’ records were searched in the database by using the terms “hepatic cyst” and “sclerotherapy”. Forty-nine patients underwent sclerotherapy for hepatic cysts during the inclusion period. Seven patients were excluded because they were followed for <1 year. A total of 42 patients with 43 hepatic cysts were enrolled in this study, which was approved by the institutional review board of the Kyungpook National University Hospital. Informed consent was obtained from all patients for invasive procedures. Patients were included into the study when one or more of the following criteria were met: (i) chronic symptoms associated with hepatic cysts that were not manageable with medical treatment; (ii) hepatic cysts that continuously enlarged to >5 cm in diameter; and (iii) complications of hepatic cysts such as laboratory test abnormalities, hemorrhage into the cyst, or infection. Patients with actively infected hepatic cysts or recent hemorrhage into hepatic cysts were excluded from the study. Other exclusion criteria included neoplastic cysts, parasitic cysts, or coagulopathy. Before cyst sclerotherapy, the patients underwent laboratory tests, upper gastrointestinal endoscopy, and colonoscopy to rule out other diseases. The size and location of the hepatic cysts were determined on the basis of contrast-enhanced dynamic CT scans of the abdomen. Magnetic resonance imaging (MRI) was performed when the diagnosis of hepatic cyst was unclear on the CT scans. The cyst volume was calculated with a sphere volume formula by using the maximal diameter. Treatment success was defined as complete or partial regression. The disappearance of the hepatic cysts and symptoms was considered complete regression. A >50% reduction in volume with ≥1 score reduction in the pain and symptom scale was considered partial regression. Pain was assessed by using the visual analogue scale (VAS): 0, no pain; 1, mild pain; 2, moderate pain; 3, strong pain; and 4, unbearable pain. Symptoms such as abdominal fullness, bloating, and early satiety were assessed by using the symptom severity score: 0, no symptom; 1, mild or intermittent; 2, moderate or often present; 3, severe or continuous. Changes in symptoms were evaluated by comparing each score before and after treatment.
Procedure protocol
The procedure was performed with patients under local anesthesia. After inserting an 18-gauge puncture needle into the cyst under US guidance, an 8.5- or 10.2-Fr pigtail catheter (Dawson-Mueller Multipurpose Drainage Catheter Ultrathane®; Cook Medical, Bloomington, IN, USA) was placed into the cyst. The cystic fluid was completely aspirated. The volume of the aspirated fluid was measured, 20 mL of which was used for bacteriologic and cytologic examinations. A cystogram was performed to rule out any communication with the biliary tree or extravasation of contrast medium into the peritoneal cavity. The contrast medium was drained, and the cyst was refilled with 99% ethanol for 20–30 min. The amount of ethanol to be used was determined according to the cyst size (corresponding to 20–30% of the volume of the aspirated fluid) and the patient’s pain response. A volume of ethanol not exceeding 500 mL was instilled into the cyst cavity. After instilling ethanol into the cystic cavity, the patient’s position was alternated between the prone, supine, and bilateral decubitus positions at 5–7 min intervals to increase contact between ethanol and the epithelial lining of the cyst. During the procedure, the patients’ blood pressure, heart rate, and oxygen saturation in arterial blood were monitored. After approximately 20–30 min of indwelling time, the ethanol was aspirated and the pigtail catheter was retained for natural drainage of cystic fluid. In 21 patients, a single prolonged session of sclerotherapy was performed because the initial drainage of cystic fluid was satisfactory. The decision to perform a single sclerotherapy session depended on the fluid consistency and cyst location. If cystic fluid was characterized by low consistency and the cyst was located in the anterior, right side of the liver, drainage of cystic fluid was considered to be relatively satisfactory.
For 22 patients, sclerotherapy with 99% ethanol was performed in multiple sessions until the daily drained fluid volume was <20 mL; when this volume was reached, the pigtail catheter was removed. If patients experienced severe pain or showed unstable vital signs during the procedure, the procedure was withheld. The multiple sessions of sclerotherapy were performed during one admission period according to the same protocol as above, and by the same operator.
After discharge, the patients were followed with US or CT examination at 1, 6, and 12 months, and then annually. Data on the presence of subjective symptoms, size of the treated hepatic cyst, and presence of symptoms were obtained at each visit.
Statistical analysis
Statistical analysis was performed by using the Statistical Package for Social Sciences software (version 20.0; SPSS, Inc., Chicago, IL, USA). Data were presented as the mean and standard deviation, or median and 25–75% interquartile range (IQR). The non-parametric Mann–Whitney U-test and χ2 or Fisher’s exact test were used to compare the differences in characteristics and treatment results between the two groups of patients. A P value of <0.05 was considered significant.
Results
Baseline characteristics of the patients and cysts.
A 76-year-old woman with a large hepatic cyst in the right lobe. (a) Contrast-enhanced abdominal computed tomography (CT) scan showing that a large 17-cm hepatic cyst has replaced the right lobe. (b) The remnant cavity visualized through a cystogram after ethanol sclerotherapy. (c) Abdominal CT scan showing the reduced cyst and re-expansion of the liver parenchyma in the right lobe.
Results and treatment outcomes of ethanol sclerotherapy for hepatic cysts.
IQR, interquartile range; SD, standard deviation.
After ethanol sclerotherapy, the patients were followed for a mean period of 33 ± 21 months. The treatment of 39 cysts (91%) was successful, with symptom resolution in 32 of 34 (94%) symptomatic patients. The hepatic cysts completely disappeared in eight patients (19%). Three patients with abnormal liver function test results later presented with normalized values without any additional symptoms. Four patients who experienced treatment failure (9%) underwent surgical treatment: three underwent surgical excision of the hepatic cyst and one underwent unroofing.
Thirteen patients (31%) experienced complications related to ethanol sclerotherapy during the procedure or within 24 h afterwards. Abdominal pain requiring analgesics was the most common adverse event and occurred in eight patients (19%). Two patients (5%) developed fever after the procedure, which spontaneously subsided. Hemorrhage into the cyst occurred in two patients (5%) during ethanol retention. In these two patients, ethanol was immediately aspirated and the procedure was aborted. Two months later, ethanol sclerotherapy was attempted again and successfully completed. One patient (2%) experienced dizziness with nausea during the procedure. Ethanol instillation was withheld until recovery, and the procedure was later completed.
The single prolonged session group was compared with the multiple session group after matching the initial sizes of cysts. Because larger cysts tend to be treated with multiple sessions, we selected cases in which cysts of the same size were treated with different methods (12 single prolonged sessions, 12 multiple sessions). Comparing the treatment outcomes between the two groups, there were no differences in volume reduction rate (96% vs. 94%, P = 0.266), final volume (50 mL vs. 50 mL, P = 0.590), or success rate (83% vs. 83%, P = 1.000); however, the catheter-indwelling period was significantly shorter in the single prolonged session group (10 ± 4 days vs. 19 ± 11 days, P = 0.014).
Discussion
Although ethanol sclerotherapy is widely performed (7–11), there is no standardized protocol concerning the frequency, interval, ethanol amount, or indwelling catheter removal for the procedure. In this study, the easiest protocol involving multiple sessions of ethanol instillation or a single session with an indwelling catheter for natural drainage was followed. The treatment outcomes of the two groups were not statistically different, thus suggesting that a single effective chemical ablation of the inner layer of cysts is more important than frequent ablations. For improved contact with cells lining the cyst, we instilled as much ethanol as possible (approximately 30% of the original cyst size) and changed the patients’ positions more aggressively.
The catheter indwelling time is shorter in a single prolonged session, which represents an important advantage because a shorter hospital stay provides substantial economic and psychological benefits to patients. However, the hospital stay for both patient groups is very long; therefore, possibilities for managing these patients as outpatients may be considered.
There were four cases of treatment failure. The first patient had a large (20 cm) hepatic cyst. Five sessions of ethanol sclerotherapy were performed before the removal of the percutaneous catheter. However, the patient visited the hospital 4 weeks later with persistent right upper abdominal pain. Abdominal CT scans showed a 13.7-cm cyst with air bubbles and high-density materials. The patient was referred for surgical resection, and the surgical specimen revealed hemorrhage with necrotic materials inside the cyst. In two cases, ethanol sclerotherapy was again performed on the cysts that had begun to increase in size after the sclerotherapy that was previously performed at other centers. One patient underwent laparoscopic cyst resection, and the other underwent a cyst unroofing procedure. The resected specimen revealed hemorrhage and calcification within the cyst. In the last case of treatment failure, the patient presented with right abdominal pain with fever after two sessions of sclerotherapy. Acute suppurative inflammation was observed in the resected cysts. In our case series, three cases of treatment failure were related to hemorrhage into the cyst after ethanol sclerotherapy, and the remaining case resulted from cyst inflammation. These cases suggest that treatment failure is closely related to the occurrence of complications after ethanol sclerotherapy of hepatic cysts.
In contrast, old hemorrhages in hepatic cysts did not seem to affect the treatment outcomes. In our case series, dark bloody cystic fluid was aspirated from five patients; however, no further bleeding was observed after fluid drainage and ethanol sclerotherapy. All of our patients were successfully treated with ethanol sclerotherapy and achieved symptom resolution.
Hemorrhagic cysts have been considered unsuitable for ethanol sclerotherapy (7); however, a recent study showed that sclerotherapy could be as effective for managing hemorrhagic hepatic cysts as for simple symptomatic hepatic cysts (11). In our study, sclerotherapy for old hemorrhagic hepatic cysts was found to be effective and safe because the complete drainage of old bloody fluid from the cyst did not interfere with the contact of ethanol at the lining of epithelial cells. In contrast, blood clots and coagulation factors from acute hemorrhage might interrupt the sclerosing effect of ethanol, and fresh blood can dilute the concentration of ethanol during the procedure, leading to treatment failure. In addition, ethanol has an inhibitory effect on platelet function and contributes to worsening hemostasis (12) in the hepatic cyst.
This study has several limitations. First, as this is a retrospective study, the clinical data were merely based on past medical records, and consequently there was a lack of randomization. Recall bias and selection bias may have affected the findings. Second, the present study included only two medical centers, which prevents the generalization of results to a broader population. Third, the patients’ symptoms were assessed by using VAS and symptom severity scoring before and after the treatment; it must be taken into consideration that patients tend to report improvement after being treated. Fourth, the changes after sclerotherapy were evaluated by using different imaging modalities (US or CT), which may have affected the interpretation of results.
In conclusion, the high rate (39 of 43, 91%) of treatment success in our study suggests that percutaneous drainage and ethanol sclerotherapy could represent a first-line therapy for large symptomatic hepatic cysts in selected patients given its high efficacy, minimal invasiveness, and safety.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Kyungpook National University Research Fund, 2010 (grant no. 201014100000).