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Original Research |
1 Department of Radiology, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st
Rd., Kaohsiung 813, Taiwan.
2 Department of Radiology, National Yang-Ming University, Taipei, Taiwan.
3 Department of Radiology, Fooyin University, Kaohsiung Hsien, Taiwan.
4 Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung,
Taiwan.
5 Department of Surgery, National Yang-Ming University, Taipei, Taiwan.
6 Department of Internal Medicine, Kaohsiung Veterans General Hospital,
Kaohsiung, Taiwan.
7 Department of Internal Medicine, National Yang-Ming University, Taipei,
Taiwan
Received April 11, 2005;
accepted after revision August 22, 2005.
Supported by grant VGHKS90-60 from Kaohsiung Veterans General Hospital.
Abstract
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MATERIALS AND METHODS. Twenty-seven patients with 31 hepatic cysts were enrolled in this study. Seventeen patients (18 cysts) were treated by alcohol retention for 4 hours (group 1) and 10 patients (13 cysts) for 2 hours (group 2). The mean diameter of the hepatic cysts was 12.4 cm (range, 8-23 cm) with a comparable size range in each group. The sclerosing agent used was 95% alcohol, and the maximum amount was limited to 200 mL. Patients changed position and vital signs were monitored every 10-15 minutes. The blood alcohol concentrations were checked hourly for 5 consecutive hours in the initial nine patients. The nonparametric Mann-Whitney U test was used to compare the difference in characteristics and treatment results of the subjects between these two groups. The level of statistical significance was set at a p value of less than 0.05.
RESULTS. All but one patient in group 2 tolerated the entire course of sclerotherapy. The mean aspirated volume and mean injected alcohol volume of the hepatic cysts were 730 mL and 138.3 mL, respectively, in group 1 patients, and 931 mL and 139 mL, respectively, in group 2 patients. The mean maximum blood alcohol concentration was 128.2 mg/dL (range, 60-199 mg/dL) at 3-4 hours after alcohol instillation. The mean posttherapy residual cystic diameter was 2.5 cm (range, 0-6 cm), with an average volume reduction rate of 98.3% and 97.7%, respectively, for patients in group 1 and group 2 after a mean follow-up period of 29.6 months (9-59 months). No statistical differences of the mean reduction rate between the two groups were noted.
CONCLUSION. Long retention of the alcohol in a single-injection technique is safe and effective. Two-hour alcohol retention has a comparable efficacy to that of 4-hour retention.
Keywords: ethanol ablation • hepatic cysts • liver • percutaneous intervention • sclerotherapy
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For renal cysts, multiple injections have been confirmed to be superior to a single injection [12]. But using a multiple-injection technique, with either a single session or multiple sessions, has several disadvantages. Multiple injections are time consuming to perform and have a potential risk of infection. Repeated aspiration and injection procedures add to patient discomfort and inconvenience. There is a risk of alcohol leakage during the second or later injections if not performed under fluoroscopy. Based on the report of Bean and Rodan [4] that alcohol would only slowly penetrate the fibrous capsule (4-12 hours), we developed a simplified ablation technique using a single alcohol injection but with prolonged retention to treat large hepatic cysts. We also compared the therapeutic efficacy of 4-hour versus 2-hour alcohol retention.
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8 cm in
diameter) in polycystic livers were treated in this study of 16 men and 11
women (age range, 43-84 years; mean age, 64.5 years). Of them, four patients
had two cysts treated 1-6 months apart. Major initial presenting complaints
included discomfort or pain over the epigastric or right upper quadrant
(n = 21), abdominal distention (n = 6), early satiety
(n = 2), and jaundice (n = 2). A simple hepatic cyst was
defined as an anechoic, unilocular fluid-filled space with imperceptible walls
showing posterior enhancement on sonography and a well-demarcated
water-attenuation lesion with no contrast enhancement on CT. Twenty-five patients underwent sonography and 23 patients underwent contrast-enhanced CT before sclerotherapy. Four patients had intrahepatic biliary dilatation on the initial imaging, and of those, elevated total bilirubin (10 and 18 mg/dL, respectively) was found in two. Five patients had abnormal serum glutamic pyruvic transaminase (SGPT) values (70-414 U/L) before sclerotherapy (normal value < 40 U/L). We used a single-session, 4-hour retention technique for 18 cysts in 17 patients (group 1) enrolled from September 1997 to July 2000. For patients enrolled between September 2000 and August 2003, we used 2-hour retention for 13 cysts in 10 patients (group 2). The basic characteristics including age, sex, and cyst size had no statistically significant difference between the two groups. Informed consent was obtained from each patient. This study was approved by the institutional review board of our hospital.
With patients under local anesthesia and in the supine position, using sonographic guidance, cyst puncture was performed with an 18-gauge needle. By Seldinger's method, a 6- to 8-French pigtail catheter was inserted percutaneously into the cyst using fluoroscopic guidance. Cystic fluid was aspirated as completely as possible through the catheter. The volume of the aspirated fluid was recorded, and some of the fluid was sent for bacteriologic and cytologic examinations. To ensure that there was no biliary communication or peritoneal extravasation, we injected diluted contrast medium into the cyst at a volume of 50% of the aspirated volume. After aspirating the test contrast medium, 5-10 mL of 2% lidocaine was injected into the cyst for pain relief. Ideally, we would inject 95% alcohol in an amount of approximately 30-40% of the aspirated volume of the hepatic cysts but never exceeding 200 mL. Smaller injected volumes were used when patients experienced intractable pain during alcohol instillation. The patient was rolled into the supine, prone, and bilateral decubitus positions at 10- to 15-minute intervals to increase contact between all surfaces of the cyst and alcohol. To ensure patient safety, we checked vital signs (blood pressure, heart rate, and partial arterial oxygen tension [PaO2]) every 10-15 minutes for 2 or 4 hours. Afterward, the residual fluid was aspirated and the catheter removed immediately. Blood alcohol concentrations (BACs) were measured hourly for the first 5 hours in the initial nine patients of group 1. Because the measured BACs in these nine patients were considered within the safety range, no further measurement was done for the subsequent patients. All procedures were performed on an inpatient basis.
The size of each cyst, both before and after sclerotherapy, was calculated by multiplying the product of the three orthogonal diameters by 0.523. Before therapy, the largest diameter of each hepatic cyst ranged from 8-23 cm (mean, 12.4 cm), with a mean cystic volume of 782.3 mL (range, 198-3,792 mL). After sclerotherapy, the residual sizes of the ablated cysts were followed by sonography or CT or both at 3- to 6-month intervals for 1 year and yearly afterward if possible. The follow-up period was defined as the time interval from sclerotherapy to the last imaging evaluation available. Hepatic function test results (serum glutamic oxaloacetic transaminase [SGOT], SGPT, and total bilirubin) were checked both before and at 3-6 months after sclerotherapy.
A commercially available statistical software package (version 10.0, SPSS) was used for analyzing patient data. Data were presented as mean ± SD. The nonparametric Mann-Whitney U test was used to compare differences in characteristics and treatment results for the subjects between the two groups. Statistical significance was defined as p < 0.05.
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All but one patient had imaging follow-up for at least 1 year with a mean follow-up period of 29.6 months (range, 9-59 months). The patient with a follow-up period of less than 1 year died of an unrelated cause 10 months after the sclerotherapy with a volume reduction rate of 97.1%. Five hepatic cysts disappeared completely. The mean residual cystic diameter after therapy was 2.5 cm (range, 0-6 cm). The average volume reduction was 98.1% (range, 83.6-100%). One patient with polycystic liver disease had two large cysts (11 and 8 cm) treated over a 6-month interval and achieved a 99.9% and 97.4% volume reduction. For the patients with abnormal SGPT values (n = 5) and elevated bilirubin values (n = 2), posttherapy values returned to normal. One patient (cyst diameter, 11 cm) with abnormal liver function (SGOT, 244 U/L; SGPT, 414 U/L; and total bilirubin, 10 mg/dL) had values return to the normal range (22 U/L, 13 U/L, and 0.6 mg/dL, respectively) after sclerotherapy despite a residual cyst with a diameter of 6 cm. Patients with normal liver function before sclerotherapy did not worsen after treatment. No significant statistical difference of the volume reduction rates between group 1 and group 2 patients was found (98.3% vs 97.7%, respectively; p = 0.309). The cyst aspirated volume, alcohol injected volume, volume reduction rates, and follow-up period in each group of patients are summarized in Table 1.
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Symptoms and signs of drunkenness with local tenderness were noted in 25 patients, flushing and headache in 17, nausea in 12, skin rash in three, and deep sleep in two during or after the procedure or both. A decrease in blood pressure of 30-50 mm Hg was noted in seven patients. Of those, sclerotherapy was terminated 30 minutes after alcohol instillation in one of the early patients, and fluid supplements or a single-dose dopamine infusion were given to the other patients without significant complications. The hospital stays were usually 1-3 days.
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Because of the secretions of the epithelial cell lining in hepatic cysts, simple percutaneous cyst aspiration or drainage can lead to a high frequency of recurrence [3]. Since the introduction of alcohol as the sclerosing agent to treat symptomatic hepatic cysts in 1985 [4], varying techniques of alcohol sclerotherapy with either multiple sessions [4-6] or a single session [7-11] have been performed. VanSonnenberg et al. [6] used a multiple-session technique with a 1- to 2-day interval between each session. In their series, the maximum was 11 sessions with the drainage catheter retained in the cyst for up to 44 days. Simonetti et al. [8] used a single alcohol injection (20- to 30-minute retention) to treat 30 simple hepatic cysts (mean diameter, 6 cm) with cyst recurrence in five patients. Thus, they recommended several repeated alcohol instillations to avoid cystic recurrence. Tikkakoski et al. [10] treated 59 symptomatic hepatic cysts with a single session consisting of 2-3 injections for each cyst. They reported that the mean diameter of the cysts decreased from 9 cm to 3 cm (range, 1-5 cm). Recently, Larssen et al. [11] used a single session with 10-minute alcohol retention to treat 10 hepatic cysts with a median volume-reduction rate of 95% (range, 49-100%).
In our series of 31 hepatic cysts, the mean maximum diameter and cyst volume were larger than that of the Tikkakoski et al. [10] (12.4 cm vs 9 cm, respectively) and Larssen et al. [11] (782 mL vs 392 mL) series before treatment. Our results were superior or at least comparable to those of the Tikkakoski et al. series (2.5 cm vs 3 cm in diameter, respectively) and the Larssen et al. series (98% vs 95% reduction rate, respectively). Our study also showed no therapeutic statistical difference between the 4-hour and 2-hour retention times. This result might be explained by one or both of two factors: almost all the cystic epithelium had been destroyed after 2 hours of alcohol retention, and the concentration of alcohol after 2 hours of retention had been diluted to a level that failed to produce further coagulation-induced necrosis of the cyst epithelium.
A collapsed cyst after drainage might have many folds with kissed areas inaccessible to the alcohol. Thus, it was not surprising that a small amount of alcohol (10-50% of the aspirated fluid as recommended in the literature) might not provide an opportunity for full contact, especially when using a short exposure time. Because of concern that residual cyst fluid might dilute the alcohol, pure alcohol was injected every 10-30 minutes for 2-3 injections in a single-session technique [2, 7, 10]. Since direct experimental proof was lacking to support the presumption that the alcohol would lose its coagulating effect after 20-30 minutes of exposure, we prolonged the alcohol exposure time to replace repeated aspiration and instillation procedures.
All the side effects of this procedure could be attributed to the symptoms and signs of drunkenness after alcohol instillation, ranging through flushing, nausea, skin rash, deep sleep, and drops in blood pressure as previously reported by either the single- or multiple-injection technique [8, 10, 11, 17]. Adinoff et al. [18] stated that severe alcohol intoxication usually occurred with BACs greater than 250 mg/dL, and hemodialysis was requested only when BACs exceeded 600 mg/dL. The highest BAC of the single-session technique in the Tikkakoski et al. [10] series (a total 60-minute retention of nondiluted alcohol) was 102 mg/dL. In our series, the mean BACs at 1, 2, and 4 hours after alcohol instillation were 64.9 mg/dL (range, 13-111 mg/dL), 97.8 mg/dL (range, 32-151 mg/dL), and 127.7 mg/dL (range, 60-199 mg/dL), respectively, which could be managed by only observation or fluid supplement or both. Gelczer et al. [17] reported the complication of hypovolemic hypotension during treatment of a hepatic cyst in one of their patients 60 minutes after injection of 80 mL of alcohol. They attributed the complication to a rare congenital deficiency of acetaldehyde dehydrogenase. In our series, hypotension (systolic pressure < 90 mm Hg) was noticed in some patients, which could occur as early as 30 minutes after alcohol instillation. It seemed that the occurrence of hypotension was not absolutely related to the alcohol injection volume or alcohol-retention time. No other complications such as pleural effusion or infection [6] occurred in our patients.
There is a rebound phenomenon of the ablated cysts with localized fluid collection shortly after sclerotherapy [2]. Seo et al. [19] reported on their experience of sclerotherapy for renal cysts that localized fluid collection still could be found during the first 1-4 months [19]. Afterward, the fluid volume decreased and achieved a steady status at around 7-12 months. This may be explained by the fact that tissue fluid that is exudated into the cyst cavity (a dead space without a barrier after ablation) will be absorbed gradually biomechanically. Thus, the optimal time for the first imaging follow-up should be at 3-6 months after the sclerotherapy, and usually 1-year imaging follow-up is sufficient.
Minocycline, tetracycline, and doxycycline are other sclerosants being used to treat hepatic cysts [6, 20]; however, the numbers treated in the studies were small (< 10), and the multiple-session technique was usually used (daily injections for several days). In their study, vanSonnenberg et al. [6] used several types of sclerosants (including alcohol alone, tetracycline, or doxycycline alone or in combination) in their patients. They stated that in the latter half of their study, alcohol became the preferred sclerosant. Hypertonic saline has been used to inactivate protoscoleces for treatment of liver hydatid cysts successfully [21]. The hypertonic status of alcohol can be diluted if absorbed, theoretically causing no systemic intoxication. The application of the hypertonic saline in treating large, simple hepatic cysts may be another alternative and warrants further evaluation with large-series study.
In conclusion, single-injection with prolonged alcohol-retention sclerotherapy (either 4 or 2 hours) had a comparable therapeutic effect with multiple injections in treating large hepatic cysts. Although the optimal alcohol-retention time in a single-injection technique still needs to be determined (120 minutes vs 90 or 60 minutes), by monitoring patients' vital signs, the prolonged alcohol-retention technique can be performed safely and efficaciously.
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