Review Article Clinical Management of Cystic Echinococcosis: State of the Art, Problems, and Perspectives

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Review Article Clinical Management of Cystic Echinococcosis: State of the Art, Problems, and Perspectives Am. J. Trop. Med. Hyg., 79(3), 2008, pp. 301–311 Copyright © 2008 by The American Society of Tropical Medicine and Hygiene Review Article Clinical Management of Cystic Echinococcosis: State of the Art, Problems, and Perspectives Thomas Junghanss, Antonio Menezes da Silva, John Horton, Peter L. Chiodini, and Enrico Brunetti* Section of Clinical Tropical Medicine, University Hospital Heidelberg, Heidelberg, Germany; Serviço de Cirugia Geral e Digestiva, Hospital de Pulido Valente, Lisbon, Portugal; Tropical Projects, Hitchin, United Kingdom;Department of Clinical Parasitology, Hospital for Tropical Diseases, London, United Kingdom; Division of Infectious and Tropical Diseases, University of Pavia, IRCCS S. Matteo Hospital Foundation, Pavia, Italy Abstract. Clinical management of cystic echinococcosis (CE) has evolved over decades without adequate evaluation of important features such as efficacy, effectiveness, rate of adverse reactions, relapse rate, and cost. CE occurs in health care environments as different as Europe/North America and resource-poor countries of the South and the East. This creates setting-specific problems in the management of patients. Furthermore, studies carried out in either of the two fundamentally different environments lack external validity, i.e., results obtained in one setting may be different from those in the other and practices that can work in one may not be applicable to the other. In this paper, we review the current management procedures of CE with particular emphasis on the evidence base and setting-specific problems. INTRODUCTION dures of CE with particular emphasis on the evidence base and setting-specific problems. Cystic echinococcosis (CE) is among the most neglected parasitic diseases. Development of new drugs and other treat- MATERIALS AND METHODS ment modalities receives very little attention, if any, and is Papers covering the subject were obtained by a Medline slow.1,2 Clinical management procedures have evolved over search of the literature published in English on this subject. decades without adequate evaluation of important features Key words were “Echinococcal cysts,” “hydatid cysts,” “cystic such as efficacy, effectiveness, rate of adverse reactions, re- echinococcosis,” “hydatidosis,” “hydatid,” “surgery,” “thia- lapse rate, and cost. bendazole,” “flubendazole,” “mebendazole,” “albendazole,” CE occurs in health care environments as different as Eu- “praziquantel,” “chemotherapy,” “PAIR,” “percutaneous rope/North America and resource-poor countries of the treatment,” “percutaneous drainage,” and “ultrasound.” Pa- South and the East. This creates setting-specific problems in pers published from 1970 to 2007 were included. The authors’ the management of patients: files were used as well. For each treatment modality, grade 3 1) In most developed countries, CE is an imported disease of and strength of the evidence is given. very low incidence and prevalence and is found almost IMAGING-BASED APPROACH exclusively in migrants from endemic regions. It thus meets the criteria of an orphan disease. As with all rare The advent of modern imaging techniques, in particular diseases two distinct subgroups are seen: ultrasound, represented a breakthrough in the diagnosis, a) Mismanaged patients because of lack of experience in treatment, and follow-up of patients with CE. With this new the health institutions where they present. tool at hand, clinicians have been striving for an imaging- b) Patients treated in centers with a special interest in CE. based classification of CE cysts for the past 25 years4–6 and to Here patients benefit from an exceptional concentra- correlate individual cyst stages with the natural history and tion of clinical experience and high technological diag- treatment-induced involution processes of the cysts. nostic and treatment facilities. Two classifications are most frequently used: the Gharbi 2) In endemic regions, predominantly settings with limited and the WHO Informal Working Group on Echinococcosis resources, patient numbers are high and medical doctors (IWGE) classification (Table 1). As shown in Table 1, the are very familiar with the disease. Whole communities do WHO classification is almost the same as Gharbi’s, with not have access to appropriate treatment, however. The Gharbi type II corresponding to CE3a and vice versa. How- choice of treatment modalities is limited because of poor ever, there are two important additions in the WHO classifi- infrastructure and shortage of equipment and drugs. In cation: the predominantly solid cyst with daughter cysts, this context, CE meets the criteria for a neglected disease. which was not explicitly included in Gharbi’s classification, has been found a place in the CE3 slot, and the types are now Furthermore, studies carried out in either of the two funda- grouped according to their biological activity (Table 1; far mentally different environments lack external validity (i.e., right column). This has important consequences for treatment results obtained in one setting may be different from those in decisions, as we will detail in the paper. Last but not least, the the other and practices that can work in one may not be WHO classification was the first to be proposed as the result applicable to the other). of the combined efforts of a group of experts, including In this paper, we review the current management proce- Gharbi himself. Controversies still exist about the natural his- tory of the cyst and whether WHO numbering of cysts types 7,8 * Address correspondence to Enrico Brunetti, Division of Infectious appropriately reflects this. An internationally accepted, and Tropical Diseases, IRCCS S. Matteo Foundation, University of standardized classification system is of paramount importance Pavia, Via Taramelli 5, 27100 Pavia, Italy. E-mail: [email protected] for uniform guidelines and comparison of data. 301 302 JUNGHANSS AND OTHERS TABLE 1 Ultrasound classification of echinococcal cysts Gharbi 1981 WHO IWGE 2001 Image Description Stage Type I CE1 Unilocular unechoic cystic lesion with double Active line sign Type III CE2 Multiseptated, “rosette-like”“honeycomb” cyst Type II CE3 A Cyst with detached membranes (water-lily-sign) Transitional Type III CE3 B Cyst with daughter cysts in solid matrix Type IV CE4 Cyst with heterogenous hypoechoic/hyperechoic Inactive contents. No daughter cysts Type V CE5 Solid plus calcified wall Comparison of the Gharbi and WHO ultrasound classifications of echinococcal cysts. A distinction between CE3a and CE3b is expressly made by the authors of this review on grounds of clinical response to PAIR and albendazole. Recent papers and our unpublished experience report that CE3b has a higher rate of relapses. With recent observations of high relapse rates in PAIR-treated CE3b cysts (see section on PT), other PTs should be explored for this cyst type. CE 3b also seems to respond poorly to albendazole (we thank Dr. W. Hosch, Department of Radiology, University Hospital Heidelberg, for contributing images in the table). WHO CE3b has not been explicitly described by Gharbi. CE3b might be classified as type III, although in the original Gharbi paper, there was no distinction between multivesiculated (honeycomb-like) cysts and cysts with daughter cysts in solid matrix. CLINICAL MANAGEMENT OF CYSTIC ECHINOCOCCOSIS 303 TREATMENT MODALITIES CURRENTLY IN USE with or without hepatic or lung resection. Peripherally located lung cysts of any size and small- to medium-sized centrally Surgery. For many years, surgery has been the only treat- located cysts can be excised without sacrificing lung paren- ment available for CE. Surgical procedures range from simple chyma. Standard radical procedures are wedge resection of puncture and aspiration of cyst content to partial resection of lung parenchyma of less than one segment, and for liver and the affected organ. We discuss here surgery of the liver and lung cysts, segmentectomy and lobectomy. Total cystectomy lungs, the two most frequently affected organs: 70% and 20%, is the ideal procedure25 to reduce complication and relapse respectively. The most common technique is total or partial rates. It can be performed by an open or a closed method cystectomy. Although surgical techniques have improved, (Napalkoff) and under videosurgery.22 With the small series there is considerable controversy as to what is the most ef- of laparoscopically treated patients available in the literature, fective technique, the role of cyst aspiration and external it is impossible to draw conclusions regarding comparison drainage, hepatic and lung resection, management of the re- with open surgery.26–28 Hepatic resection and lung segment- sidual cavity in CE of the liver, cyst recurrence after surgery, ectomy/lobectomy are rarely performed.14,29 Radical proce- and high rates of complications and mortality related to re- dures bear greater intraoperative risks, with less postopera- 9–14 operation in recurrent disease. An immediate cure is tive complications and relapses.9,10,15,25,30 Conservative pro- claimed for surgical treatment of liver cysts, but even with cedures are preferred for lung cysts, with radical procedures radical procedures, this is far from being achieved, with mor- such as segmentectomy and lobectomy necessary for ex- bidity, mortality, and relapse rates of 32%, 8%, and 20%, tended parenchymal involvement severe pulmonary suppura- 9,10,15 respectively. For surgery of lung cysts, reported morbity tion and complications such as pulmonary fibrosis, bron- ranges between
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