Percutaneous drainage and combined praziquantel-albendazole therapy: a novel approach for the treatment of simple echinococcal liver cysts

Abstract

Cystic echinococcosis (CE) is a worldwide helminthic zoonosis causing serious disease in humans. The WHO Informal Working Group on Echinococcosis recommends a stage-specific treatment approach of hepatic CE that facilitates the decision on what therapy option is most appropriate. Percutaneous aspiration, instillation of a scolicide, e.g., ethanol or hypertonic saline, and subsequent re-aspiration (PAIR) have been advocated for treating medium-size unilocular WHO-stage CE1 cysts. PAIR can pose a risk of toxic cholangitis because of spillage of ethanol in the case of a cysto-biliary fistula or of life-threatening hypernatriaemia when hypertonic saline is used. The purpose of our study is to develop an alternative, safe, minimally invasive method to treat CE1 cysts, avoiding the use of toxic topic scolicides.

We opt for percutaneous drainage (PD) in four patients: the intrahepatic drainage catheter is placed under CT-fluoroscopy, intracystic fluid is aspirated, and the viability of intracystic echinococcal protoscolices is assessed microscopically. Oral praziquantel (PZQ) is added to albendazole (ABZ) instead of using topical scolicidals.

Protoscolices degenerate within 5 to 10 days after PZQ co-medication at a cumulative dosage of 250 to 335 mg/kg, and the cysts collapse. The cysts degenerate, and no sign of spillage nor relapse is observed in the follow-up time of up to 24 months post-intervention.

In conclusion, PD combined with oral PZQ under ABZ coverage is preferable to PAIR in patients with unilocular echinococcal cysts.

Zusammenfassung

Die zystische Echinokokkose (CE) ist eine weltweit verbreitete zoonotische Helminthose, die schwere Erkrankungen beim Menschen hervorruft. Die WHO Informal Working Group on Echinococcosis empfiehlt einen stadiengerechten Therapieansatz der hepatischen CE, der die Entscheidung über die geeignetste Behandlungsoption erleichtert. Die perkutane Aspiration, Instillation eines Skolizids, beispielsweise von Ethanol oder hypertoner Kochsalzlösung, und darauffolgender Re-Aspiration (PAIR) wurde für einfache Zysten mittlerer Größe im WHO-Stadium 1 empfohlen.

Die PAIR beinhaltet Risiken wie das einer toxischen Cholangitis durch das Verbringen von Ethanol in eine zystobiliäre Fistel oder einer lebensbedrohenden Hypernatriaemie bei Verwendung hypertoner Kochsalzlösung. Das Ziel unserer Studie war es, eine alternative, sichere, minimal invasive Methode für die Behandlung von CE1 Zysten zu entwickeln, bei der der Einsatz topischer Skolizide vermieden werden kann.

Wir entschieden uns für eine perkutanen Drainage (PD) bei vier Patienten: ein intrahepatischer Katheter wurde unter CT-fluoroscopischer Kontrolle eingelegt, die intracystische Flüssigkeit fluid wurde aspiriert und die Vitalität der intracystischen Protoscolices mikroskopisch analysiert. Praziquantel (PZQ) per os wurde zur Albendazolmedikation (ABZ) hinzugefügt anstatt topische Skolizide zu verwenden.

Die Protoscolices degenerierten innerhalb 5 bis 10 Tagen nach PZQ Ko-medikation nach Erreichen einer kumulativen Dosis von 250 bis 335 mg/kg und die Zysten kollabierten. Die Zysten degenerierten ohne ein Zeichen der Disseminierung von Zystenflüssigkeit oder eines Rückfalls über bis zu 24 Monaten nach der Intervention.

Zusammenfassend ist eine PD in Kombination mit PZQ p.o. unter ABZ-Abdeckung einer PAIR bei Patienten mit unilokulären Echinokokkenzysten vorzuziehen.

Keywords

cystic echinococcosis - Echinococcus granulosus - interventional radiology - percutaneous treatment - praziquantel - albendazole

Schlüsselwörter

Zystische Echinococcosis - Echinococcus granulosus - Interventionelle Radiologie - Perkutane Behandlung - Praziquantel - Albendazol

Publication History

Received: 23 March 2023

Accepted: 29 March 2023

Article published online:
20 September 2023

• References

• 1 World Health Organization. “Echinococcosis Fact sheet N°377”, last accessed 25 August 2021.
• 2 Brunetti E, Kern P, Vuitton DA. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop 2010; 114: 1-16 DOI: 10.1016/j.actatropica.2009.11.001. (PMID: 19931502)
• 3 WHO Informal Working Group on Echinococcosis (IWGE). PAIR: Puncture, Aspiration, Injection, Re-Aspiration. WHO/CDS/CSR/APH/2001 2001; 30: 1-10
• 4 WHO Informal Working Group on Echinococcosis (IWGE). Meeting 15 –16 December 2016: 27 March 2017. WHO/HTM/NTD/NZD/2017.01.
• 5 Brunetti E, Tamarozzi F, Macpherson C. et al. Ultrasound and Cystic Echinococcosis. Ultrasound Int Open 2018; 4: 1-9 DOI: 10.1055/a-0650-3807. (PMID: 30364890)
• 6 Velasco-Tirado V, Alonso-Sardón M, Lopez-Bernus A. et al. Medical treatment of cystic echinococcosis: systematic review and meta-analysis. BMC Infect Dis 2018; 18: 1-19 DOI: 10.1186/s12879-018-3201-y. (PMID: 29976137)
• 7 Stojkovic M, Gottstein B, Junghanss T. Echinococcosis. Manson’s Tropical Diseases 2014; 795-819
• 8 Aktan AO, Yalin R. Preoperative albendazole treatment for liver hydatid disease decreases the viability of the cyst. Eur J Gastroenterol Hepatol 1996; 8: 877-879 (PMID: 8889454)
• 9 Velasco-Tirado V, Romero-Alegria A, Pardo-Lledías J. et al. Management of cystic echinococcosis in the last two decades: what have we learned?. Trans R Soc Trop Med Hyg 2018; 112: 207-215
• 10 Morris DL, Taylor DH. Optimal timing of post-operative albendazole prophylaxis in E. granulosus. Ann Trop Med Parasitol 1988; 82: 65-66 DOI: 10.1080/00034983.1988.11812210. (PMID: 3401071)
• 11 Lötsch F, Naderer J, Skuhala T. et al. Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data. Parasitol Res 2016; 115: 2995-3001 DOI: 10.1007/s00436-016-5054-x. (PMID: 27085708)
• 12 Stojkovic M, Zwahlen M, Teggi A. et al. Treatment response of cystic echinococcosis to benzimidazoles: A systematic review. PLoS Negl Trop Dis 2009; 3 (09) e524 DOI: 10.1371/journal.pntd.0000524. (PMID: 19787039)
• 13 Ayles HM, Corbett EL, Taylor I. et al. A combined medical and surgical approach to hydatid disease: 12 years’ experience at the Hospital for Tropical Diseases, London. Ann R Coll Surg Engl 2002; 84: 100-105 (PMID: 11995745)
• 14 Krige JE, Millar AJ, Rode H. Fatal hypernatraemia after hypertonic saline irrigation of hepatic hydatid cysts. Pediatr Surg Int 2002; 18 (01) 64-65 DOI: 10.1007/s003830200015. (PMID: 11793068)
• 15 Michalodimitrakis M, Nathena D, Mavroforou A. et al. Fatal hypernatraemia after laparoscopic treatment of hydatid liver cyst: medical and legal concerns of a rare complication. Forensic Sci Int 2012; 219: e16-e18 DOI: 10.1016/j.forsciint.2011.11.029. (PMID: 22209544)
• 16 Kuzmanovska B, Kartalov A, Kuzmanovski I. et al. Hypernatremia-induced neurologic complications after hepatic hydatid cyst surgery: pretreat to prevent. Med Arch 2019; 73 (05) 356-358 DOI: 10.5455/medarh.2019.73.356-358. (PMID: 31819311)
• 17 Khuroo MS, Wani NA, Javid G. et al. Percutaneous drainage compared with surgery for hepatic hydatid cysts. N Engl J Med 1997; 337 (13) 881-887
• 18 Men S, Yücesoy C, Edgüer TR. et al. Percutaneous treatment of giant abdominal hydatid cysts: long-term results. Surg Endosc 2006; 20: 1600-1606 DOI: 10.1007/s00464-005-0627-2. (PMID: 16823651)
• 19 Morris DL, Richards KS, Clarkson MJ. et al. Comparison of albendazole and praziquantel therapy of Echinococcus granulosus in naturally infected sheep. Vet Parasitol 1990; 36: 83-90 DOI: 10.1016/0304-4017(90)90096-t. (PMID: 2382392)
• 20 Piens MA, Persat F, May F. et al. Praziquantel in human hydatidosis. Evaluation by preoperative treatment; article in French. Bull Soc Pathol Exot Filiales 1989; 82: 503-512 (PMID: 2805182)
• 21 Homeida M, Leahy W, Copeland S. et al. Pharmacokinetic interaction between praziquantel and albendazole in Sudanese men. Ann Trop Med Parasitol 1994; 88: 551-559
• 22 Cobo F, Yarnoz C, Sesma B. et al. Albendazole plus praziquantel versus albendazole alone as a pre-operative treatment in intra-abdominal hydatisosis caused by Echinococcus granulosus. Trop Med Int Health 1998; 3: 462-466 DOI: 10.1046/j.1365-3156.1998.00257.x. (PMID: 9657508)
• 23 Mohamed AE, Yasawy MI, Al Karawi MA. Combined albendazole and praziquantel versus albendazole alone in the treatment of hydatid disease. Hepatogastroenterology 1998; 45: 1690-1694 (PMID: 9840130)
• 24 Urrea-París MA, Moreno MJ, Casado N. et al. In vitro effect of praziquantel and albendazole combination therapy on the larval stage of Echinococcus granulosus. Parasitol Res 2000; 86: 957-964 DOI: 10.1007/pl00008526. (PMID: 11133110)
• 25 Haralabidis S, Diakou A, Frydas S. et al. Long-term evaluation of patients with hydatidosis treated with albendazole and praziquantel. Int J Immunopathol Pharmacol 2008; 21: 429-435
• 26 Bygott JM, Chiodini PL. Praziquantel: Neglected drug? Ineffective treatment? Or therapeutic choice in cystic hydatid disease?. Acta Trop 2009; 111: 95-101 DOI: 10.1016/j.actatropica.2009.04.006. (PMID: 19375409)
• 27 Gavidia CM, Gonzalez AE, Barron EA. et al. Evaluation of oxfendazole, praziquantel and albendazole against cystic echinococcosis: a randomized clinical trial in naturally infected sheep. PLoS Negl Trop Dis 2010; 4: e616 DOI: 10.1371/journal.pntd.0000616. (PMID: 20186332)
• 28 Morris DL, Richards KS, Chinnery JB. Protoscolicidal effect of praziquantel-in-vitro- and electron microscopical studies on Echinococcus granulosus. J Antimicrob Chemother 1986; 18: 687-691 DOI: 10.1093/jac/18.6.687. (PMID: 3818494)
• 29 Heller T, Wallrauch C, Kaminstein D. et al. Case report: cysticercosis: sonographic diagnosis of a treatable cause of epilepsy and skin nodules. Am J Trop Med Hyg 2017; 97 (06) 1827-1829 DOI: 10.4269/ajtmh.17-0257. (PMID: 29016298)
• 30 Stojkovic M, Rosenberger KD, Steudle F. et al. Watch and wait management of inactive cystic echinococcosis – does the path to inactivity matter – analysis of a prospective patient cohort. PLoS Negl Trop Dis 2016; 10: 1-10
• 31 Lissandrin R, Tamarozzi F, Mariconti M. et al. An approach for inactive echinococcal cyst of the liver: an update. Am J Trop Med Hyg 2018; 99: 375-379 DOI: 10.4269/ajtmh.18-0164. (PMID: 29869600)
• 32 Doğru D, Kiper N, Ozçelik U. et al. Medical treatment of pulmonary hydatid disease: for which child?. Parasitol Int 2005; 54: 135-138
• 33 Thapa B, Sapkota R, Kim M. et al. Surgery for parasitic lung infestations: roles in diagnosis and treatment. J Thorac Dis 2018; 10: S3446-S3457 DOI: 10.21037/jtd.2018.08.32. (PMID: 30505532)
• 34 Cattaneo L, Manciulli T, Cretu CM. et al. Cystic Echinococcosis of the bone: A European4multicenter study. Am J Trop Med Hyg 2019; 100: 617-621
• 35 Neumayr A, Troia G, de Bernardis C. et al. Justified concern or exaggerated fear: the risk of anaphylaxis in percutaneous treatment of cystic echinococcosis-a systematic literature review. PLoS Negl Trop Dis 2011; 5: e1154 DOI: 10.1371/journal.pntd.0001154. (PMID: 21695106)
• 36 Richter J, Profis E, Holtfreter MC. et al. Anaphylactic shock ensuing therapeutic puncture of an echinococcal cyst. Parasitol Res 2015; 114: 763-766 DOI: 10.1007/s00436-014-4275-0. (PMID: 25547080)
• 37 Li Y, Zheng H, Cao X. et al. Demographic and clinical characteristics of patients with anaphylactic shock after surgery for cystic echinococcosis. Am J Trop Med Hyg 2011; 85: 452-455
• 38 Richter J, Lindner A, Geisel D. et al. Treatment of a giant hepatic echinococcal cyst with percutaneous drainage and in vivo assessment of the protoscolicidal effect of praziquantel. Clin J Gastroneterol 2021; 14 (03) 888-892
• 39 Baily G, Garcia HH. Other cestode infections: intestinal cestodes, cysticercosis, other larval cestode infections. Manson’s Tropical Diseases 2014; 820-832
• 40 Narra R, Maestri M, Budke CM. et al. Costs associated with surgically treated cases of abdominal cystic echinococcosis: A single center’s experience from 2008 to 2014, Pavia, Italy. Am J Trop Med Hyg 2016; 95: 405-459