Published online before print December 20, 2002, 10.1148/radiol.2262011574
(Radiology 2003;226:573-576.)
© RSNA, 2003
Renal Cyst Ablation with n-Butyl Cyanoacrylate and Iodized Oil in Symptomatic Patients with Autosomal Dominant Polycystic Kidney Disease: Preliminary Report1
Seung Hyup Kim, MD,
Min Whan Moon, MD,
Hak Jong Lee, MD2,
Jung Suk Sim, MD3,
Sun Ho Kim, MD and
Curie Ahn, MD
1 From the Departments of Radiology (Seung Hyup Kim, M.W.M., H.J.L., J.S.S., Sun Ho Kim) and Internal Medicine (C.A.), Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea; Institute of Radiation Medicine, Seoul National University Medical Research Center, Korea; and Clinical Research Institute, Seoul National University Hospital, Korea. Received September 24, 2001; revision requested October 29; final revision received May 6, 2002; accepted May 7. Supported by Seoul National University Research Fund 2001. Address correspondence to Seung Hyup Kim (e-mail: kimsh@radcom.snu.ac.kr).
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ABSTRACT
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Fifty renal cysts in 14 patients with autosomal dominant polycystic kidney disease (ADPKD) were treated with percutaneous needle aspiration and intracystic injection of a mixture of n-butyl cyanoacrylate and iodized oil in a ratio of 1:2. At follow-up of 1–12 months, symptoms improved in 12 (86%) of 14 patients, and 25 (81%) of 31 cysts decreased more than 50% in diameter. This procedure appears to be feasible and may be an effective modality in ablation of renal cysts in patients with ADPKD.
© RSNA, 2003
Index terms: Kidney, cysts, 81.311 • Kidney, diseases, 81.3121 • Kidney, interventional procedures, 81.1262, 81.1269 • Sclerotherapy
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INTRODUCTION
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Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by innumerable bilateral renal cysts that involve both the renal cortex and medulla. It has an occurrence rate of one in 200–1,000 individuals and is a relatively common cause of renal failure (1). At least three genes are involved in ADPKD, and the severity of the disease varies not only from genetic type to genetic type but also from patient to patient. It is thought that the central element in cyst formation is epithelial hyperplasia (2).
In patients with this disease, usually after 30 years of age, renal cysts grow and cause renal parenchymal compression that, in turn, causes slow but inevitable progression to chronic renal failure (3–5). Hypertension occurs in 50%–75% of the patients with ADPKD before serious loss of renal function; the occurrence of hypertension can be explained by the activation of the renin-angiotensin system due to local renal ischemia caused by cyst expansion (6,7). Other complications in these patients include cyst bleeding, cyst infection, calyceal obstruction, and calculi. However, the most common complaints of the patients with ADPKD are abdominal distention and related symptoms, such as indigestion.
To relieve the symptoms related to the abdominal distention, cyst volume should be reduced, but no specific medical treatment is available for this purpose. Among interventional radiologic procedures, simple aspiration of the cyst is ineffective because usually cyst fluid accumulates again after aspiration (8). For sclerotherapy of the renal cysts, various techniques and sclerosing agents have been tried (8–22). Most commonly, a small catheter is inserted and absolute alcohol is used for sclerotherapy, and the value of this technique in the treatment of simple cysts has been well established (9,10). However, this technique is not easy to use in the treatment of renal cysts in patients with ADPKD because there are too many cysts into which catheters would have to be inserted.
n-Butyl cyanoacrylate (NBCA) (Histoacryl-Blue; Braun, Melsungen, Germany), which initially was used for sutureless closure of smooth and fresh skin wounds, has been used for embolization of vascular lesions of various parts of the body and for endoscopic management of bleeding and fistulas (23–26). If NBCA can be used and is effective in renal cyst ablation, it will be helpful in treating renal cysts in patients with ADPKD. Since this technique is simple and catheter insertion is not necessary, we can, therefore, treat multiple cysts in the same session of treatment. The objective of this study was to assess the feasibility and effectiveness of cyst ablation by using NBCA in patients with ADPKD.
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Materials and Methods
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During 14 months from June 2000 to July 2001, NBCA treatment was performed in 50 renal cysts in 14 patients with ADPKD. This study was approved by the institutional review board of the Seoul National University Hospital, Korea. The patients were eight women and six men and were between 36 and 64 years old (mean age, 46 years). All patients underwent computed tomography (CT), and the diameter of the cysts was 3–8 cm (mean, 5 cm). All 14 patients complained of abdominal and/or flank discomfort due to growing renal cysts. The patients who had relatively acute symptoms, such as bleeding or infection, were not included in the study. Nine patients were hypertensive and six were azotemic (ie, the serum creatinine level was > 1.4 mg/dL [123.76 µmol/L]). Three patients underwent percutaneous catheter drainage and alcohol sclerotherapy in three cysts 1–3 years before this treatment. Informed consent was obtained before the procedure was performed in all patients. All procedures were performed on an in-patient basis because of the possibility of complications. Hospitalization for each session of the treatment was 1–4 days (mean, 3 days).
After sterile preparation, a 22-gauge needle was inserted into a cyst (we tried to select the largest cyst) with ultrasonographic (US) guidance. Cyst fluid was aspirated as completely as possible, and the volume of aspirated fluid was measured. Then a mixture of 0.5 mL of NBCA and 1 mL of iodized oil (Lipiodol; Laboratoire Guerbet, Roissy, France) was injected. Immediately before the injection of this mixture, the needle was flushed with a small amount of 5% dextrose water solution to prevent the contact of NBCA with tissue fluid in the lumen of the needle. After the injection of the mixture of NBCA and iodized oil, a conventional radiograph was obtained. Then the same procedure was repeated for the next cyst. One to nine renal cysts were treated in each patient. We measured the longest diameter of radiopacity on a radiograph obtained after injection of the mixture and ensured that the injected material was confined within the cyst. We also evaluated complications related to the procedure. The procedure was technically successful in all 50 renal cysts. No patient complained of pain at the time of injection. Patients were not sedated.
The time needed for the procedure, which included positioning and draping the patient, was approximately 10 minutes; that for US-guided needle insertion into a cyst was approximately 5 minutes; that for aspiration of the fluid, depending on the amount of fluid removed, was 5–10 minutes; that for preparation and injection of the mixture of NBCA and iodized oil was approximately 5–10 minutes; and that for obtaining the radiograph was negligible. Although we did not specifically measure the procedure time, we estimated it to be 15–25 minutes for treating each cyst, excluding the time needed for positioning and draping the patient.
Clinical follow-up was performed at 1–12 months (mean, 6.5 months) in all 14 patients, and it was performed with CT in eight patients with 31 cysts at 3–12 months (mean, 7.1 months, contrast material–enhanced CT in five patients and nonenhanced CT in three) (Figure). The patients were asked by one author (C.A.) whether there were any changes (ie, if they were better or worse or if they observed no change) in the subjective symptoms after the procedure. The changes in the blood pressure and serum creatinine levels were also checked. Size changes were evaluated at CT by two radiologists (Seung Hyup Kim, Sun Ho Kim) together. The procedure was regarded successful at follow-up CT when the diameter of the cyst was less than 50% of the initial diameter.
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Figure a.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure b.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure c.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure d.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure e.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure f.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure g.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Figure h.ADPKD in a 37-year-old man. (a-c) Transverse contrast-enhanced CT scans from cranial to caudal levels show multiple cysts in both kidneys. Cyst ablation was performed in two cysts (1,2) in the right kidney and in two cysts (3,4) in the left kidney. (d) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated right cysts (1,2). (e) Posteroanterior radiograph obtained after the procedure shows opacities that represent the mixture of NBCA and iodized oil in the treated left cysts. (f-h) Follow-up transverse nonenhanced CT scans from cranial to caudal levels obtained 11 months after the procedure show shrunken cysts (1-4) filled with the mixture of NBCA and iodized oil.
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Results
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The volume of aspirated fluid ranged between 10 and 200 mL (mean, 51 mL). The radiographs obtained immediately after the injection of the mixture of NBCA and iodized oil showed radiopacities, with the longest diameter ranging between 1 and 4 cm. In no case were there complications related to the procedure.
With clinical follow-up, the symptoms related to the cysts improved in 12 (86%) of 14 patients, whereas the symptoms were the same as they were before the procedure in the remaining two patients. No patient complained of worsening of the symptoms after the procedure. At follow-up CT, the procedure was successful (ie, the diameter of the cyst was less than 50% of that before treatment) in 25 (81%) of 31 cysts. There were no substantial changes in blood pressure and serum creatinine level after the procedure.
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Discussion
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ADPKD is characterized by innumerable bilateral renal cysts and is an important cause of chronic renal failure and hypertension. Cystic disease of the liver is commonly associated with ADPKD, reportedly in 30%–75% of cases (3–5). Most of the patients with ADPKD complain of abdominal discomfort and related symptoms due to growth of the cysts in the kidney and liver. Other organs that may have cysts include the pancreas, the spleen, the thyroid gland, the parathyroid gland, the ovary, the endometrium, the seminal vesicle, the lung, the brain, the pituitary gland, the pineal gland, the breast, the peritoneum, and the epididymis (5).
Percutaneous ablation of a benign renal cyst is indicated if the lesion causes pain, obstruction, hypertension, or pressure atrophy of the adjacent parenchyma. Investigators in earlier reports described the value of intracystic instillation of iophendylate (Pantopaque; Lafayette Pharmacol, Lafayette, Ind) for renal cyst sclerotherapy (11,21). Treatment with various agents has been tried, and these agents include absolute ethanol (8,10), ethanolamine oleate (13), povidone iodine (16), acetic acid (17), dextrose solution, quinacrine hydrochloride (12,13), tetracycline (14,18), minocycline (19), glucose, phenol (9), bismuth phosphate (20), and fibrin glue (22).
Among these sclerosing agents, absolute ethanol is most commonly used. Alcohol fixes the epithelial lining cells and renders them nonviable in 1–3 minutes. The absorption of alcohol through the cyst wall is known to be minimal (14). A small pigtail catheter is placed in the cyst, and a diagnostic study is performed. For permanent obliteration of the cyst lining, as much of the cyst fluid as possible is aspirated, and 25%–50% of the cyst volume is replaced with alcohol for 15–30 minutes. The procedure should be repeated daily or twice a day according to the amount of the fluid drained. If a cystic lesion to be ablated communicates with the renal collecting system, a sclerosing agent should not be injected, because it may cause fibrotic stricture of the collecting system (14). Although this technique of alcohol sclerotherapy is known to be effective in treating simple renal cysts (9,10), it is difficult to be used for the treatment of the renal cysts in patients with ADPKD because there are too many cysts into which catheters should be inserted.
The use of NBCA is another possible way to treat renal cysts in patients with ADPKD, because it is simple and catheter insertion is not necessary. Ionic solutions, such as tissue fluid or blood, immediately polymerize NBCA into a solid substance with a stable connection to the tissue. In most of the previous studies (23–25), NBCA was mixed with iodized oil to minimize the exothermic reaction of NBCA, to delay and control the polymerization time, and to provide radiopacity of iodized oil for follow-up imaging. Investigators in these studies most commonly used a mixture of NBCA and iodized oil in a ratio of 1:2, and we also used that same mixture. Some researchers reported that the addition of tungsten into this mixture further prolonged the reaction time of NBCA (26).
During our study, we used a few technical precautions in introducing the mixture of NBCA and iodized oil into the cyst. First, we aspirated cyst fluid as completely as possible. To achieve this, the needle tip should be monitored with US so that it remains in the center of the cyst during aspiration. Once the cyst fluid has been completely aspirated with a 10-mL syringe, we tried further aspiration by using a 2-mL syringe with repeated holding of respiration at inspiration and expiration. Usually a few milliliters of fluid more could be aspirated with this technique. Second, the mixture of NBCA and iodized oil is viscous; therefore, it should be injected with very gentle steady pressure so that the syringe is not disconnected from the needle. The operator and the assistants should put on glasses to protect their eyes. Caution also should be used so that the needle tip should not be moved during the injection of the mixture.
In this preliminary study, the technique of renal cyst ablation with NBCA is simple and effective in reducing the volume of renal cysts in patients with ADPKD. It was 100% successful technically, 86% effective at symptom relief clinically, and 81% successful at imaging follow-up. These success rates were similar to those reported in previous studies in which alcohol and other sclerosing agents were used in the treatment of simple cysts in non-ADPKD (9,10). There were no complications, and we believe that the procedure might, thus, be performed on an outpatient basis.
There were some limitations in this study, and these included a small number of cysts and of patients and a short follow-up period. For investigation of possible changes in blood pressure and serum creatinine level after the procedure, as well as the recurrence of the cysts, long-term follow-up will be necessary. Another limitation of this study is that this treatment was tried only for renal cysts and did not include the liver cysts that are often a more prominent feature than renal cysts in ADPKD patients. Despite these limitations, we conclude that this technique is feasible as an alternative to reduce the volume of renal cysts in patients with ADPKD.
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FOOTNOTES
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2 Current address: Department of Radiology, Samsung Cheil Hospital and Women’s Healthcare Center, Seoul, Korea. 
3 Current address: Department of Radiology, National Cancer Center, Kyunggi-do, Korea.
Abbreviations: ADPKD = autosomal dominant polycystic kidney disease,
NBCA = n-butyl cyanoacrylate
Author contributions: Guarantors of integrity of entire study, all authors; study concepts, Seung Hyup Kim, C.A.; study design, Seung Hyup Kim; literature research, Seung Hyup Kim, H.J.L.; clinical studies, Seung Hyup Kim, M.W.M., H.J.L., C.A.; data acquisition, Seung Hyup Kim, M.W.M., H.J.L., C.A.; data analysis/interpretation, Seung Hyup Kim, Sun Ho Kim; manuscript preparation, Seung Hyup Kim, J.S.S., Sun Ho Kim; manuscript definition of intellectual content, Seung Hyup Kim; manuscript editing, Seung Hyup Kim, J.S.S., C.A.; manuscript revision/review, H.J.L., M.W.M., C.A.; manuscript final version approval, all authors.
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ABSTRACT
INTRODUCTION
