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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 21
| Issue : 1 | Page : 19-25 |
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Safety of ultrasound-guided percutaneous injection of alcohol as a scolicidal agent for the treatment of liver hydatid cysts
V John Samuel1, Arul Babu1, Vinu Moses1, MJ Aparna2, Munawwar Ahmed1, George M Varghese3, Philip Joseph2, Shyamkumar N Keshava1
1 Department of Interventional Radiology, Christian Medical College Hospital, Vellore, Tamil Nadu, India
2 Department of Hepatobiliary Surgery, Christian Medical College Hospital, Vellore, Tamil Nadu, India
3 Department of Infectious Diseases, Christian Medical College Hospital, Vellore, Tamil Nadu, India
| Date of Submission | 27-Jun-2022 |
| Date of Decision | 16-Sep-2022 |
| Date of Acceptance | 13-Oct-2022 |
| Date of Web Publication | 17-Jan-2023 |
Correspondence Address:
Dr. Shyamkumar N Keshava
Department of Interventional Radiology, Christian Medical College Hospital, Vellore, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/cmi.cmi_71_22
Background: Hydatid disease is a health problem in the developing world. Percutaneous therapy with various scolicidal agents has been described; however, there is a paucity of literature on the use of absolute alcohol injection without reaspiration as a sole scolicidal agent. The study carried out in a tertiary hospital aimed to prospectively evaluate the safety and outcomes of ultrasound-guided percutaneous injection of alcohol for liver hydatid cyst. Methodology: Consecutive patients with liver hydatid cysts were evaluated with ultrasound, classified according to the WHO classification between June 2012 and January 2020. Eligible patients underwent ultrasound-guided percutaneous therapy after three courses of oral albendazole. Patients having elevated cyst fluid bilirubin levels were excluded. Patients who underwent percutaneous alcohol injection were followed up clinically and with imaging. Data were entered in Microsoft Excel spreadsheet and analyzed. Results: Fifty-two consecutive patients with hydatid cyst were evaluated during the study. Among these, 27 patients underwent percutaneous alcohol injection. Follow-up data were available for 25 patients. There was a favorable imaging outcome in 21/25 (84%). One patient developed anaphylaxis during cyst access, which was managed medically with an uneventful recovery. No instances of cholangitis or sepsis following injection were observed. Conclusion: Percutaneous alcohol injection therapy for liver hydatid cysts is a minimally invasive, safe, and an effective procedure in selected group of patients.
Keywords: Alcohol sclerotherapy, hepatic hydatid cyst, percutaneous injection
How to cite this article:
Samuel V J, Babu A, Moses V, Aparna M J, Ahmed M, Varghese GM, Joseph P, Keshava SN. Safety of ultrasound-guided percutaneous injection of alcohol as a scolicidal agent for the treatment of liver hydatid cysts. Curr Med Issues 2023;21:19-25 |
How to cite this URL:
Samuel V J, Babu A, Moses V, Aparna M J, Ahmed M, Varghese GM, Joseph P, Keshava SN. Safety of ultrasound-guided percutaneous injection of alcohol as a scolicidal agent for the treatment of liver hydatid cysts. Curr Med Issues [serial online] 2023 [cited 2023 May 31];21:19-25. Available from: https://www.cmijournal.org/text.asp?2023/21/1/19/367861 |
| Introduction | |  |
Hydatid disease of liver/echinococcosis is a zoonotic infection with incidental transmission of metacestode stage to humans. Liver remains the most common organ affected followed by lung.[1] Surgery combined with medical treatment remains the common method of management of liver hydatid cysts.[2],[3] Percutaneous therapy was thought to be of high risk, considering the possibility of leakage of cyst contents causing anaphylaxis or peritoneal spill. Adjunct antiechinococcal oral medical therapy has helped establish the percutaneous therapy as a more favorable therapeutic option.[4],[5],[6],[7] Percutaneous techniques are less invasive and carry significantly less morbidity. It can be performed under local anesthesia with intravenous sedation, with significantly reduced procedure times, cost, and duration of hospitalization. Although percutaneous therapy has been in vogue since the early 90's, the practice has not been uniform, and the literature pertaining to the use of absolute alcohol as a sclerosant is sparse. Our study aimed to assess the safety and effectiveness of combined medical and alcohol sclerotherapy in treating hepatic hydatid disease. The workup and patient selection criteria for alcohol sclerotherapy are discussed, and our institutional protocol is illustrated.
| Methodology | | |
The Institutional Review Board approval was obtained.(IRB Min.No: 7955 dated August 22, 2012).
Study setting
The study was conducted at a tertiary care hospital.
Study design
This was an interventional-observational study.
Participants and time period
Patients who underwent sclerotherapy between June 2012 and January 2020.
Diagnostic criteria
Diagnosis of liver hydatid disease was made on characteristic features on ultrasonography (USG), computed tomography (CT), and/or magnetic resonance imaging (MRI). The cyst type was classified according to the WHO IWGE classification using USG to help identify active cysts.[8] Patients planned for percutaneous sclerotherapy were given a course of oral albendazole for three courses prior to procedure.
Procedure
The procedure was performed under a short inpatient admission. Patients were counseled, and informed written consent was obtained. Preprocedure laboratory evaluation including bleeding parameters (prothrombin time, international normalized ratio, activated partial thromboplastin time, and platelets) and liver function test were performed. All procedures were performed under USG guidance (Toshiba Xario), and the cysts were accessed by Seldinger technique using an 18G needle, and a 6F pigtail catheter was placed over a guide wire with no tissue dilatation to ensure placement well into the cyst. Single-puncture catheters can be used alternatively. The tract within the liver was selected in such a way that the cyst was accessed through at least a few centimeters of normal liver parenchyma to prevent spillage into the peritoneal cavity. Approximately 10 cc of the cyst fluid was aspirated initially and sent for laboratory evaluation for bilirubin levels and scolices/hydatid hooklets. With prior information to the laboratory about the procedure, results were made ready within 10–15 min. The cyst fluid was allowed to drain as much as possible in the meantime.
Before instillation of alcohol, cyst fluid bilirubin level report was collected. A cyst bilirubin level of more than 1.2 mg/dL was considered to indicate a possible cystobiliary communication and regarded as a contraindication to the procedure.[9] The amount of alcohol injected was 1/3rd–1/4th volume of aspirated cyst fluid, but not exceeding the recommended safe limit. Reaspiration was performed if the injected volume of alcohol was large. When the sclerosant injected was of small volume, it was allowed to remain within the cyst with no reaspiration. Pig-tail catheter was removed soon after the injection of alcohol. The presence of multiple cysts, multiple daughter cysts, or a large volume cyst is not a contraindication. Each cyst be treated individually in the same sitting, and sclerosant is believed to act on the daughter cysts within the parent cyst. Even large cysts can be treated without exceeding the safe upper volume limit of sclerosant injected. If the cyst is located well within the liver parenchyma, no peritoneal communication is expected, and this was also confirmed in the preprocedure imaging. Fluoroscopy and contrast agent were not employed in our study. If there was any doubt in the preprocedure evaluation, MRI was performed to rule out peritoneal disease. Procedure can be performed even in peripherally located cysts, as on ultrasound, it is prudent to find a safe tract through normal liver parenchyma and also as the cyst is not kept under tension after aspiration. Postprocedure, patients can be discharged after 24 h if there are no complications. Patients were given instructions to report immediately in case of fever, severe pain, or any other symptoms. They were advised to come for follow-up in the next few days and also to continue oral albendazole.
Statistics
Data were prospectively entered in MS Excel spreadsheets and analyzed.
Outcome assessment
Follow-up was performed using USG and/or cross-sectional imaging. Treatment response was assessed based on change in volume as well as morphology of the cyst. A volume reduction of more than 60% at 3-month follow-up was considered improvement, while no change or increase in the volume of the cyst at 6-month follow-up was considered treatment failure. New finding of detachment of the inner membrane, heterogeneous imaging transformation of the cyst, disappearance of daughter cysts, complete resolution of the cyst, and a solid pseudotumor-like appearance were also considered morphologic features suggesting favorable treatment response.
Postprocedural complications were classified as major (anaphylaxis, iatrogenic biliary fistula, cyst infection, intra-abdominal abscess, and sepsis) and minor (postprocedure pain, catheter breakage, etc.,).
| Results | | |
A total of 52 patients were enrolled for the procedure. Seven did not undergo the procedure which included four who did not return after counseling, two patients chose surgical option, and one had not completed the medical therapy course. Of the remaining 45, all had USG. In 12 patients, cyst fluid bilirubin level was above the cutoff value indicating cystobiliary communication, and hence, alcohol injection was deferred. In such patients, drainage and irrigation of the cavity with normal saline were performed and referred for surgical management. Four patients had thick purulent aspirate on cyst puncture, suggestive of infected hydatid cyst, and procedure was abandoned. One patient developed anaphylaxis after cyst puncture, and another had suspected peritoneal communication confirmed on fluoroscopy, and hence, sclerotherapy was not performed. Twenty-seven patients' samples showed favorable cyst fluid bilirubin level and underwent sclerotherapy. Seventeen were male (62.9%), and 10 were female (37.1%). Based on the WHO IWGE classification, one (3.7%) was CL type (anechoic unilocular cyst), 16 (59.3%) were CE1 type (with echoes or hydatid sand), and eight (29.6%) were CE3 type (with floating membranes or multiple daughter cysts within the larger mother cyst). There was one (3.7%) each of CE2 and CE4 types (heterogeneous appearance). Although the CE4 type cyst would be inactive according to the classification, patient was taken up for percutaneous therapy, since the patient had already undergone surgery elsewhere and it recurred.
The volume of the smallest cyst was nearly 26 cc, and the largest cyst was a giant cyst of nearly 4000 cc. The aspirate was yellowish in nine patients and clear in the other patients. The volume of cyst fluid aspirated ranged between 15 and nearly 4000 cc. Cyst fluid bilirubin values among patients who underwent alcohol injection ranged between “nil” to 1.1 mg/dL. The volume of alcohol injected varied between 9 and 65 cc. Seventeen out of the 27 (62.9%) showed echinococcal scolices/hooklets, while they were not seen in the other 10 patients. Those who did not show scolices/hooklets were also treated as some had residual large cyst from previous operation for liver hydatid, others were determined, and hydatid cysts based on typical imaging features and were also symptomatic.
In the postprocedure period, one patient had severe pain and four patients developed fever. These complications were medically managed. Hospital stay varied from 1 to 4 days. Seventeen patients stayed for 2 days, eight patients for a day, one patient for 3 days, and another for 4 days. The median hospital stay was 2 days. All patients were followed up and reassessed with ultrasound imaging. The follow-up period varied from 1 to 48 months. Two patients did not return. The volume reduction percentage ranged between 29.5% and almost 100% with a mean of 69.8%. Among the 25 patients who were followed up, 19 (76%) showed a favorable resolution of >60% volume reduction, while six (24%) showed <60% reduction.
On the morphologic assessment of cyst on follow-up of the 25 patients, six (24%) showed detachment of membranes (new finding), five (25%) patients showed solid appearance, eight (36%) showed heterogeneous appearance, one (8.3%) patient had near complete resolution, and one (8.3%) had complete resolution of the cyst. Overall, the number of patients who showed favorable response to treatment based on USG appearance was 21/25 (84%). Combining the size and appearance criteria for good response on follow-up, all 19 patients who had shown more than 60% volume reduction had favorable imaging appearance as well. Two patients showed favorable imaging response, but less than 60% volume reduction. These patients remained asymptomatic, and hence, no further treatment was performed, were advised follow-up. It is of interest to note that these two patients had smaller cyst volumes of 50 and 110 cc, respectively. Hence, in small-volume cysts (<150 cc), change in morphology can be more of an indicator than mere reduction in size.
One patient had anaphylaxis immediately after the placement of pigtail catheter and was resuscitated effectively with an uneventful recovery. The pigtail drain was retained. She was observed in the intensive care unit for 24 h and shifted to regular ward. She underwent surgical treatment during the same admission and discharged. In two patients, the tip of the pigtail drain broke during removal. In one patient, it was left behind after confirming its position in the residual cavity with USG. In the other patient, the broken pigtail fragment was removed over the wire using a vascular access sheath dilator.[10] Both patients had an uneventful hospital stay and had no symptoms related to catheter breakage on follow-up. [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5] demonstrate different types of liver hydatid cysts injected and their outcome on follow-up. | Figure 1: (a) A 74-year-old patient with CE1 type cyst with a volume of approximately 200 cc. (b) Follow-up at 4 months showing near complete resolution.
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 | Figure 2: (a) A 21-year-old patient with CE3 type cyst showing with membranes within. (b) Follow-up image showing marked reduction in the volume and more heterogeneous appearance of the cyst at the end of 3 months.
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 | Figure 3: (a) A 36-year-old patient with USG images showing a well-defined CL type cyst with trilaminar membrane. (b) Following injection, there is detachment of membranes. USG: Ultrasonography.
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 | Figure 4: (a) A 60-year-old patient with USG image showing CE3 type hydatid cyst and daughter cysts. (b) Follow-up image showing disappearance of daughter cysts and heterogeneous appearance with reduced volume of the cyst. USG: Ultrasonography.
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 | Figure 5: Images showing steps involved in the procedure – inserting aspiration needle, guide wire followed by 6F pigtail catheter placement well into the cyst cavity.
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| Discussion | | |
In percutaneous injection sclerotherapy of liver hydatid, selecting the right patient is essential for a successful treatment. The WHO-IWGE classifies hydatid cysts into three classes based on imaging as follows: active (CL – unilocular anechoic cyst; CE1 – unilocular cyst with mobile echoes; CE2 – multilocular or with daughter cysts), transitional (CE3 – with floating membranes), and inactive (CE4 – pseudotumor like; CE5 – with calcified wall).[8] Active and transitional cysts can be treated effectively by percutaneous alcohol injection. Percutaneous therapy with adjunct albendazole has been shown to be equally effective as surgery with the added advantage of lesser morbidity, prevention of further progression and dissemination of the disease, and reduced cost.[11],[12] The addition of antiparasitic therapy prior to cyst drainage inactivates the cyst and reduces the chance of intraperitoneal seeding that may occur during cyst puncture or inadvertent cyst rupture during the procedure. Furthermore, the combination of drainage with antiparasitic therapy has shown to reduce recurrence rates.[12] Hence, the decision between surgical or percutaneous therapy can be based on the available expertise and patient's choice of treatment option. Recurrence after surgery can also be an indication for percutaneous therapy. The recommended timing of treatment is after the completion of a full course of oral albendazole therapy.
Ultrasound is easily available, fast, and cost-effective imaging technique that can be used in pretreatment classification and for follow-up. MRI/CT scan is not recommended in all cases, however, can be used for better characterization when ultrasound findings are inconclusive or cannot be performed due to patient-related limitations like morbid obesity or severe hepatic steatosis obscuring details. CT scan will help in identifying cyst calcification which may be an indicator for inactive cyst.
Percutaneous injection therapy can be performed under local anesthesia and mild intravenous sedation with monitoring of vital signs. Risk of anaphylaxis is very less as shown in our study and others reviewed, and shown in [Table 1] (one case in each study with varying sample size). | Table 1: Comparison of the agent used, follow-up period, success rates, and complications in a few prior studies with our study
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The presence of cystobiliary communication is a contraindication for percutaneous injection therapy and can lead to chemical cholangitis. A few indicators of cystobiliary communication have been proposed in the literature like large cyst size, very high cyst fluid bilirubin levels, high white cell count, etc., however, demonstration of communication by fluoroscopy after intracavitory contrast injection has been described as the best method.[13] Balloon occlusion of the cystobiliary communication identified on percutaneous cholangiogram, followed by sclerosant injection, is reported in the literature.[14] However, identification of a significant cyst-biliary fistula is not always possible as most communications are occult.[9]
Different scolicidal agents have been used in percutaneous therapy such as hypertonic saline (15%–20%), absolute alcohol (95%), normal saline, mixture containing hypertonic saline and albendazole, mixture of silver nitrate, mebendazole, and albendazole.[12]
The landmark publication on percutaneous treatment “PAIR” therapy using repeated aspirations and instillations of hypertonic saline till the microscopic sample did not show scolices.[11] Hypertonic saline, which is established as a safe agent, is not easily available in many hospitals. Hence, it was a need for us to establish an alternative percutaneous technique with absolute alcohol in treating these liver hydatid cysts. Second, the end point of therapy mentioned during percutaneous therapy is the disappearance of scolices which would need reconsideration. As we have seen in our case series, scolices could be only demonstrated in less than half of the patients in the first aspirated sample. The logistic challenges include repeated examination of the fluid under microscopy. We selected alcohol as a scolicidal agent as our team was familiar with using the agent as a sclerosant for treating vascular anomalies. The safe upper limit has been mentioned as 0.5–1 mL/kg body weight while treating vascular anomalies. Hydatid cyst in liver is a contained space compared to vascular anomaly; hence the dispersion of alcohol into the body is expected to be slower, and chances of systemic complications such as nephrotoxicity and accelerated pulmonary hypertension are remote. In addition, alcohol as a sclerosant is very potent.
In our study, the successful treatment based on cyst size and imaging appearance, as described previously, was observed in 84% of our patients. This was comparable with prior published data from Khuroo et al. who report 89.7% success rate in their population using hypertonic saline.[7] A comparison of our data with other studies is provided in the table. We encountered a single major complication of anaphylaxis prior to alcohol injection, which was managed medically. Although four of our patients had transient pyrexia in the postprocedure period, none developed complications like cyst infection or rupture. We did not encounter any patient who developed jaundice or cholangitis postprocedure in our study; this could be partly attributed to our strict patient selection criteria with regards to suspected cyst-biliary fistula. An algorithm for percutaneous alcohol sclerotherapy is given in [Figure 6]. Within the follow-up period of our study (average 24 months), we did not have any patient requiring repeated injection; however, it remains to be seen if there will be recurrence later requiring reinjection during longer follow-up. | Figure 6: Algorithm showing steps of percutaneous alcohol injection sclerotherapy.
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Small sample size (n = 27) was a limitation of the study. Another limitation of the study is the lack of uniformity in follow-up. A longer follow-up period would be ideal, since hydatid cysts in liver need a longer time to demonstrate a good response to treatment.
| Conclusion | | |
Percutaneous injection of absolute alcohol under USG guidance is safe and effective to treat liver echinococcal cysts in selected groups of patients. It is cost effective and can be performed under local anesthesia and mild IV sedation. Expertise is required for the management of complications.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Ethical statement
All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional review board.
| References | | |
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| 2. | Alonso Casado O, Moreno González E, Loinaz Segurola C, Gimeno Calvo A, González Pinto I, Pérez Saborido B, et al. Results of 22 years of experience in radical surgical treatment of hepatic hydatid cysts. Hepatogastroenterology 2001;48:235-43.  |
| 3. | Gollackner B, Längle F, Auer H, Maier A, Mittlböck M, Agstner I, et al. Radical surgical therapy of abdominal cystic hydatid disease: Factors of recurrence. World J Surg 2000;24:717-21. |
| 4. | Eckert J, Gemmell MA, François-Xavier M, Pawlowski ZS. World Health Organization. WHO/OIE manual on echinococcosis in humans and animals: A public health problem of global concern/edited by Eckert J, et al. World Organisation for Animal Health 2001. https://apps.who.int/iris/handle/10665/42427. |
| 5. | Bret PM, Fond A, Bretagnolle M, Valette PJ, Thiesse P, Lambert R, et al. Percutaneous aspiration and drainage of hydatid cysts in the liver. Radiology 1988;168:617-20. |
| 6. | Mueller PR, Dawson SL, Ferrucci JT Jr., Nardi GL. Hepatic echinococcal cyst: Successful percutaneous drainage. Radiology 1985;155:627-8. |
| 7. | Khuroo MS, Zargar SA, Mahajan R. Echinococcus granulosus cysts in the liver: Management with percutaneous drainage. Radiology 1991;180:141-5. |
| 8. | WHO Informal Working Group. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 2003;85:253-61. |
| 9. | Unalp HR, Baydar B, Kamer E, Yilmaz Y, Issever H, Tarcan E. Asymptomatic occult cysto-biliary communication without bile into cavity of the liver hydatid cyst: A pitfall in conservative surgery. Int J Surg 2009;7:387-91. |
| 10. | Premkumar M, Chiramel GK, Keshava SN. Retrieval of retained pigtail in the liver. Indian J Radiol Imaging 2020;30:376-8. [Full text] |
| 11. | Filice C, Pirola F, Brunetti E, Dughetti S, Strosselli M, Foglieni CS. A new therapeutic approach for hydatid liver cysts. Aspiration and alcohol injection under sonographic guidance. Gastroenterology 1990;98:1366-8. |
| 12. | Smego RA Jr., Bhatti S, Khaliq AA, Beg MA. Percutaneous aspiration-injection-reaspiration drainage plus albendazole or mebendazole for hepatic cystic echinococcosis: A meta-analysis. Clin Infect Dis 2003;37:1073-83. |
| 13. | Khuroo MS, Dar MY, Yattoo GN, Zargar SA, Javaid G, Khan BA, et al. Percutaneous drainage versus albendazole therapy in hepatic hydatidosis: A prospective, randomized study. Gastroenterology 1993;104:1452-9. |
| 14. | Varro J, Mathew L, Athyal RP, Khafagy AH. Percutaneous alcohol sclerotherapy of a hepatic hydatid cyst after balloon occlusion of a large biliary communication. Med Princ Pract 2011;20:477-9. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1]
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