Over the past 30 years, benzimidazoles have increasingly been used to treat cystic echinococcosis (CE). The efficacy of benzimidazoles, however, remains unclear. We systematically searched MEDLINE, EMBASE, SIGLE, and CCTR to identify studies on benzimidazole treatment outcome. A large heterogeneity of methods in 23 reports precluded a meta-analysis of published results. Specialist centres were contacted to provide individual patient data. We conducted survival analyses for cyst response defined as inactive (CE4 or CE5 by the ultrasound-based World Health Organisation [WHO] classification scheme) or as disappeared. We collected data from 711 treated patients with 1,308 cysts from six centres (five countries). Analysis was restricted to 1,159 liver and peritoneal cysts. Overall, 1–2 y after initiation of benzimidazole treatment 50%–75% of active C1 cysts were classified as inactive/disappeared compared to 30%–55% of CE2 and CE3 cysts. Further in analyzing the rate of inactivation/disappearance with regard to cyst size, 50%–60% of cysts <6 cm responded to treatment after 1–2 y compared to 25%–50% of cysts >6 cm. However, 25% of cysts reverted to active status within 1.5 to 2 y after having initially responded and multiple relapses were observed; after the second and third treatment 60% of cysts relapsed within 2 y. We estimated that 2 y after treatment initiation 40% of cysts are still active or become active again. The overall efficacy of benzimidazoles has been overstated in the past. There is an urgent need for a pragmatic randomised controlled trial that compares standardized benzimidazole therapy on responsive cyst stages with the other treatment modalities.
BackgroundImaging plays the key role in diagnosing and staging of CE. The description of CE-specific imaging features and the WHO CE cyst classification is based on ultrasound. The reproducibility of the ultrasound-defined features of CE cysts is variable in MR- and CT-imaging. This is of particular importance for cysts that are not accessible by US and because of the increasing availability and overuse of CT and MR imaging.Methodology/Principal FindingsRetrospective analysis of patients with abdominal CE cysts of an interdisciplinary CE clinic who had CT and/or MRI scans performed additionally to US imaging. All images were read and interpreted by the same senior radiologist experienced in the diagnosis of CE. US, CT and MR images were staged according to the WHO classification criteria. The agreement beyond chance was quantified by kappa coefficients (κ). 107 patients with 187 CE cysts met the inclusion criteria. All cysts were assessed by US, 138 by CT, and 125 by MRI. The level of agreement beyond chance of the individual CE stages 1–4 was clearly lower for CT, with κ ranging from 0.62 to 0.72, compared to MRI with values of κ between 0.83 and 1.0. For CE5 cysts CT (κ = 0.95) performed better than MRI (κ = 0.65).ConclusionsUltrasound remains the corner stone of diagnosis, staging and follow up of CE cysts. MRI reproduces the ultrasound-defined features of CE better than CT. If US cannot be performed due to cyst location or patient-specific reasons MRI with heavily T2-weighted series is preferable to CT.
Cystic echinococcosis is a worldwide disease caused by larval stages of the parasite Echinococcus granulosus (canine tapeworm). In clinical practice, staging of cyst development by ultrasonography (US) has allowed treatment options to be tailored to individual patient needs. However, the empirical correlation between cyst morphology and parasite viability is not always dependable and has, until now, required confirmation by invasive assessment of cyst content by light microscopy (LM), for example. Alternatively, high-field 1H MRS may be used to examine cyst fluid ex vivo and prepare detailed quantitative metabolite profiles, enabling a multivariate metabolomics approach to cyst staging. One-dimensional and two-dimensional 1H and 1H/13C MRS at 600 MHz (14.1 T) was used to analyze 50 cyst aspirates of various US and LM classes. MR parameters and concentrations relative to internal valine were determined for 44 metabolites and four substance classes. The high concentrations of succinate, fumarate, malate, acetate, alanine, and lactate found in earlier studies of viable cysts were confirmed, and additional metabolites such as myo-inositol, sorbitol, 1,5-anhydro-D-glucitol, betaine, and 2-hydroxyisovalerate were identified. Data analysis and cyst classification were performed using univariate (succinate), bivariate (succinate vs fumarate), and multivariate partial least squares discriminant analysis (PSL-DA) methods (with up to 48 metabolite variables). Metabolic classification of 23 viable and 18 nonviable cysts on the basis of succinate alone agreed with LM results. However, for seven samples, LM and MRS gave opposing results. Reclassification of these samples and two unclassified samples by PLS-DA prediction techniques led to a set of 50 samples that could be completely separated into viable and nonviable MRS classes with no overlap, using as few as nine variables: succinate, formate, malate, 2-hydroxyisovalerate, acetate, total protein content, 1,5-anhydro-D-glucitol, alanine, and betaine. Thus, future noninvasive in vivo applications of MRS would appear promising.
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