• View in gallery

    Schematic representation of the natural history of cystic echinococcosis (CE) cysts and of the stage-specific approach to hepatic CE cysts based on the World Health Organization (WHO) Informal Working Group on Echinococcosis (IWGE) Expert Consensus, as implemented in Pavia WHO Collaborating Center for Clinical Management of CE. ABZ = albendazole; PA (IR) = puncture, aspiration (injection, re-aspiration); PC = percutaneous catheterization.

  • View in gallery

    Minimal requirements protocol (on the left) and optimal situation protocol (on the right) for puncture, aspiration, injection of scolicidal agent, re-aspiration (PAIR). CT = computed tomography; ELISA = enzyme-linked immunosorbent assay; IgM = immunoglobulin M.

  • View in gallery

    Schematic comparison of the standard PAIR procedure followed by 1 month albendazole prophylaxis (top; gray bar represents albendazole intake), ideal modified procedure of percutaneous aspiration without injection of the scolicidal agent followed by a full course of albendazole therapy (middle; gray bar represents albendazole intake), and the procedure evaluated in this retrospective study associating percutaneous aspiration without injection of the scolicidal agent to a full course of albendazole therapy started either at variable time before (gray and dashed bars) or right after (white bar) the procedure (middle). ABZ = albendazole; PA = puncture, aspiration; w/o = without.

  • View in gallery

    Flowchart showing the selection of the study population extracted from the Echinococcosis Database. Gray boxes indicate patients included in the evaluation of the procedure effectiveness. CL = cystic lesion; PT = percutaneous treatment.

  • View in gallery

    Duration in months of ABZ course before and after puncture. White bars represent the duration of ABZ course before the first puncture. Gray bars represent duration of ABZ course after the first puncture. Black bars represent duration of ABZ course after the second puncture. Black stars indicate the time of first cyst solidification after the first puncture. White star indicates the time of second cyst solidification after the first puncture. Patient 13 had a 2-month pre-puncture ABZ course 116 months before the puncture. Note the scale divergence compared with the rest of the chart and indicated by the black stripes inside the white bar.

  • View in gallery

    Cumulative percentage of punctured cysts reaching the CE4 stage. Black dots represent the end of follow-up of cysts.

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Preliminary Evaluation of Percutaneous Treatment of Echinococcal Cysts without Injection of Scolicidal Agent

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  • 1 WHO-Collaborating Centre for Clinical Management of Cystic Echinococcosis, Pavia, Italy;
  • | 2 Division of Infectious Tropical Diseases, San Matteo Hospital Foundation, Pavia, Italy;
  • | 3 Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy

Puncture, Aspiration, Injection of scolicidal agent, Re-aspiration is the most widely used percutaneous treatment of cystic echinococcosis (CE). Among its perceived risks is chemical sclerosing cholangitis, a serious complication due to the caustic effect of the scolicidal solution on the biliary tree, when a patent cystobiliary fistula occurs. To simplify the protocol, we decided to omit injection and reaspiration of the scolicidal agent and to implement a full course of albendazole (ABZ) therapy instead of the routine 1-month ABZ prophylaxis. We searched our databases for patients with CL (Cystic Lesion, suspected for CE), CE1, and CE3a cysts treated between October 2007 and January 2017 with percutaneous aspiration followed by at least 1 month of oral ABZ and with an ultrasound follow-up of at least 6 months. Fifteen patients matched our inclusion criteria. Follow-up ranged from 7 to 75 months. The oral ABZ course after the aspiration procedure ranged from 1 to 18 months. Eleven subjects (73.3%) had undergone a course of ABZ before the percutaneous procedure (min 15 days, max 16 months). Ten cysts (62.5%) had reached solidification (stage CE4) in 3 to 69 months. Four other cysts (26.7%) remained stable in stage CE3a, whereas two cysts (13.3%) reactivated to stage CE3b. Procedural perioperative complications occurred in 13.3% of patients, whereas complications during the follow-up occurred in 20% of patients. These proof-of-concept preliminary results are overall comparable with those reported in the literature for other percutaneous treatments, both in terms of response rate, relapse rate, and morbidity.

INTRODUCTION

Cystic Echinococcosis (CE) is a zoonotic infection with a worldwide distribution and of great medical and veterinary concern, caused by the larval stage of Echinococcus granulosus species complex. CE has been described as chronic, complex, and neglected.1 Its clinical presentation in humans is extremely variable, ranging from asymptomatic to potentially fatal manifestations.24

The therapeutic options available for CE have changed over the years. Initially, the only possibility was surgical removal of the cyst. Subsequently, at the end of the past century, new approaches were made available, thanks to the introduction of benzimedazole drugs (mebendazole in the 1970s and albendazole (ABZ) in the 1980s), and the development and implementation of percutaneous treatments (PTs) in the mid-1980s. PTs of CE include various imaging-guided techniques that aim at the evacuation of the cyst content and inactivation of the germinal layer, the inner cellular layer of the cyst wall, using a scolicidal agent injected into the cyst cavity. Because of the neglect of CE, there is a dearth of randomized, prospective trials comparing treatment options, and its therapeutic management still relies on strength of recommendation B (moderate) and quality of evidence III (from opinion of respected authorities, based on clinical experience, descriptive studies or reports of committees).5 The World Health Organization (WHO) Informal Working Group on Echinocococcosis (IWGE) recommends a stage-specific approach for the clinical management of hepatic uncomplicated cysts, based on the WHO-IWGE cyst classification in six stages (CE1 to CE5, with the CE3 stage divided into CE3a and CE3b). A schematic representation of the WHO-IWGE CE cyst classification and of the stage-specific approach to their clinical management, as implemented in our center, is shown in Figure 1.

Figure 1.
Figure 1.

Schematic representation of the natural history of cystic echinococcosis (CE) cysts and of the stage-specific approach to hepatic CE cysts based on the World Health Organization (WHO) Informal Working Group on Echinococcosis (IWGE) Expert Consensus, as implemented in Pavia WHO Collaborating Center for Clinical Management of CE. ABZ = albendazole; PA (IR) = puncture, aspiration (injection, re-aspiration); PC = percutaneous catheterization.

Citation: The American Journal of Tropical Medicine and Hygiene 97, 6; 10.4269/ajtmh.17-0468

In 1985, Mueller and colleagues reported for the first time a successful percutaneous drainage of a hepatic echinococcal cyst in one patient.6 In the following years, this success encouraged several studies to fine-tune the percutaneous approach, first experimenting on sheep then applying percutaneous techniques on humans in endemic countries such as Tunisia, Turkey, and Italy.712 The results of these studies set the foundation for the development of the Puncture, Aspiration, Injection and Re-aspiration (PAIR) technique, the most widely used PT, whose protocol was codified in a technical document of the WHO in 2001.13 Figure 2 shows the step-by-step PAIR protocol using minimal requirements and the optimal situation versions.13

Figure 2.
Figure 2.

Minimal requirements protocol (on the left) and optimal situation protocol (on the right) for puncture, aspiration, injection of scolicidal agent, re-aspiration (PAIR). CT = computed tomography; ELISA = enzyme-linked immunosorbent assay; IgM = immunoglobulin M.

Citation: The American Journal of Tropical Medicine and Hygiene 97, 6; 10.4269/ajtmh.17-0468

PAIR has been increasingly used for hepatic and abdominal CE, and even if large, randomized placebo-controlled trials on the use of this technique have never been carried out,14 the safety and effectiveness of PAIR, when applied to selected cases, have been confirmed by an increasing number of studies comparing PAIR with either surgery or medical treatment indicating a significantly lower morbidity and mortality rates, duration of hospital stay, and costs compared with surgery.1519 PAIR is recommended by the WHO-IWGE Expert Consensus document for the treatment of uncomplicated abdominal CE1 and CE3a cysts, where its response rate is > 80%.5,20,21 Modifications of the original PAIR protocol have been proposed for the treatment of giant cysts (> 10 cm), where permanent catheterization appears safe and effective.22 However, the only head to head comparison of the two techniques did not show significant differences in their effectiveness.23 As in the case of surgery, PAIR has to be followed imperatively by the administration of a peri-interventional prophylaxis with ABZ for 1 month.5

The widespread application of PTs has been limited by the fear of potential complications, such as anaphylactic shock, dissemination of protoscolices, and sclerosing cholangitis resulting from the contact of scolicidal agents with the epithelium of the biliary ducts in case of the presence of cysto-biliary fistulas. The occurrence of lethal anaphylaxis, according to a systematic review of the literature, has been estimated in 0.04% of procedures, and the prophylactic peri-interventional use of ABZ from right before until 1 month after the procedure controls the risk of recurrence.24,25 Various scolicidal agents have been used in PAIR, the most commonly used being 95% ethanol and 20% saline, and their in vitro efficacy has been assessed.2628 Chemical sclerosing cholangitis is due to the caustic effect of the scolicidal solution on the biliary tree, when a cystobiliary fistula becomes patent. Although this occurrence was reported in patients undergoing intracystic injection of sclerosing agent during surgeries and was later recreated in animal models, there is no published report of PAIR-related chemical sclerosing cholangitis. In any case, to avoid this serious complication, the PAIR protocol requires ruling out intracystic-biliary communication, whether with a dipstick test for bilirubin or better with a cystography with contrast medium.2932

As described previously, the straightforward acronym PAIR leaves out and conceals an important intermediate step: the individuation of communications between the cyst and the biliary tree. This step requires, in optimal conditions (Figure 2, right panel) radiological equipment often not available in many low resource settings. The minimal requirement procedure (Figure 2, left panel) is quite hazardous if we consider the toxicity of the scolicidal agents and the risk of causing a sclerosing cholangitis.

At the end of 2007, we started to implement a simplified PAIR protocol, avoiding cystography to detect cysto-biliary communications, and omitting injection and reaspiration of the scolicidal agent but combining puncture and aspiration with a full course of ABZ therapy, ideally of 6 months, completed either right before the procedure, or after the puncture if the patients started ABZ therapy before the procedure (Figure 3). This not only simplifies and shortens the PT protocol, making it accessible in contexts where the individuation of communications between the cyst and the biliary tree is not feasible, (e.g., low-resource settings), but also avoids any risk of sclerosing cholangitis or other tissue damage from spillage of histolesive solutions. The fundamental difference between this approach and that indicated in the WHO-IWGE documents5,13 is that ABZ is administered here as a treatment of the cyst itself, as opposed to the 1-month prophylaxis used after the standard PAIR procedure and started only a few hours/days before, and aiming just to prevent secondary peritoneal echinococcosis that might derive from the spillage of hydatid fluid with protoscoleces during the procedure. Here, we evaluated retrospectively the clinical data from routine procedures of patients who underwent this modified percutaneous treatment in our center.

Figure 3.
Figure 3.

Schematic comparison of the standard PAIR procedure followed by 1 month albendazole prophylaxis (top; gray bar represents albendazole intake), ideal modified procedure of percutaneous aspiration without injection of the scolicidal agent followed by a full course of albendazole therapy (middle; gray bar represents albendazole intake), and the procedure evaluated in this retrospective study associating percutaneous aspiration without injection of the scolicidal agent to a full course of albendazole therapy started either at variable time before (gray and dashed bars) or right after (white bar) the procedure (middle). ABZ = albendazole; PA = puncture, aspiration; w/o = without.

Citation: The American Journal of Tropical Medicine and Hygiene 97, 6; 10.4269/ajtmh.17-0468

MATERIALS AND METHODS

Data were extracted from the patients’ electronic database of the WHO Collaborating Center for Clinical Management of Cystic Echinococcosis. Inclusion criteria were 1) cysts in stage CE1/CE3a/CL at puncture—CL cysts (cystic lesions, i.e., unilocular fluid-filled cysts without pathognomonic signs of parasitic etiology on ultrasound) were later staged as CE1/CE3a at follow-up and included in the cohort if their parasitic etiology was confirmed; 2) cysts that underwent a PT (either aspiration or catheterization) without intracystic injection of a scolicidal agent, (PTs carried out between October 1, 2007 and January 31, 2017); 3) patients who received at least 1 month of ABZ therapy after the procedure; 4) patients who were followed up for at least 6 months after aspiration or removal of the catheter. This last inclusion criterion was applied for the assessment of the effectiveness of the procedure (effectiveness cohort), whereas complications were considered at all times independently of the length of the follow-up.

For all patients meeting the inclusion criteria, extracted data included 1) demographic information (age, sex, nationality [Italian versus other], and age at PT); 2) cyst characteristics (total number, stages [preprocedure and during the follow-up], size [pre-procedure and during follow-up], and location [organ, segment if hepatic]); 3) procedures (total number per patient, number per cyst, type [aspiration versus catheterization],and duration of catheterization [days]); 4) hydatid cyst fluid (HCF) analysis (viable protoscolices versus not viable protoscolices/only hooklets); 5) ABZ treatment (duration prepuncture [months]; duration postpuncture [months], time elapsed between the end of last ABZ therapy and puncture [months]); and 6) follow-up and outcome (length [months], solidification [months to], complications [type and time of appearance in relation to the procedure]).

Quantitative data were described as numbers and percentages; qualitative data as medians with interquartile range (IQR).

RESULTS

The results of database search are schematized in Figure 4. Among the 38 patients having CL cysts or parasitic cysts in CE1/CE3a stage, which underwent a PT (PAIR, aspiration or catheterization) in our center, 15 patients meeting inclusion criteria were retrieved and included in the descriptive evaluation of the procedure effectiveness.

Figure 4.
Figure 4.

Flowchart showing the selection of the study population extracted from the Echinococcosis Database. Gray boxes indicate patients included in the evaluation of the procedure effectiveness. CL = cystic lesion; PT = percutaneous treatment.

Citation: The American Journal of Tropical Medicine and Hygiene 97, 6; 10.4269/ajtmh.17-0468

The mean age of patients on first percutaneous treatment was 38.7 years (median 32, range 4–80); 60% of the subjects were males (N = 9). The country of origin of patients was Italy (N = 5) and Romania (N = 5), whereas the remaining five patients had five different countries of origin: Albania, Bulgaria, Moldova, Morocco, and Ukraine. Cysts characteristics are summarized in Table 1.

Table 1

Overview of the cyst characteristics, from the pretreatment baseline to the last follow-up time point

Patient progressive numberNo. of cysts punctured (included in the effectiveness cohort)N° of procedures per cyst (included in the effectiveness cohort)Stage pre-punctureSize pre-puncture (mm)Type of procedureDuration of catheterization (days)F-U after puncture (months)Stage at last F-U visitSize at last F-U visit (mm)
112CE3aCE3a127140AspCat603828CE3a<90
211CE3a121Cat5041CE458
311CE3a117Cat1530CE4104
412CE1CE3a120159CatCat2125750CE469
521CE3aCE3a8555CatAsp73131CE3a<CE46754
611CE3a110Asp7CE3a113
71*1CE1133Cat2225CE416
811CL102Cat156CE477
911CE3a90Cat120CE473
1011CL64Asp10CE3a<43
1111CE1100Asp40CE3b69
1211CE1104Asp75CE451
1311CE171Asp31CE454
1411CL128Asp10CE3b120
1511CE3a154Cat4869CE488

FU = follow-up; CE3a< = CE3a stage with smaller diameter than pre-puncture; Cat = catheterization; Asp = aspiration. Gray boxes highlight the data regarding the second procedure of a single cyst that underwent two percutaneous procedures. In the first and next to last column, in bold are indicated the patients and cysts for which the procedure can be classified as successful.

Patient 7 underwent the puncture of a second cyst not indicated in the table because the follow-up was shorter than 6 months (this second cyst was removed surgically after its rupture).

Patient 11 underwent a second percutaneous treatment of a second cyst that had to be interrupted for the onset of a major anaphylactic reaction.

Patient 12 underwent a second percutaneous treatment of the same cyst that had to be interrupted for the onset of rash and intense pain.

The subjects included in the cohort harbored a total number of cysts (punctured and not punctured) ranging from one to five (mean 1.8). Eight patients (53.3%) had only one cyst (the one then punctured), whereas the remaining seven patients (46.7%) had two or more cysts. Twelve subjects (80%) underwent puncture of only one cyst once, two subjects (13.3%) had the same cyst punctured in two different procedures, whereas one subject (6.7%) had two different cysts punctured once each, for a total of 16 cysts punctured and a total of 18 PT procedures (mean 1.1 procedures per cyst and 1.2 procedures per patient). When two procedures were performed on the same patient, either the puncture of two different cysts or two punctures of the same cysts, on average 5.7 months (range 0–10), elapsed between procedures.

Of these 16 punctured cysts, 14 (87.5%) were located in the liver, 1 (6.2%) was in the pelvis, and 1 (6.2%) in the spleen. Regarding the stage of these cysts before the first PT, 8 (50%) were CE3a, 5 (31.2%) were CE1, and 3 (18.7%) were CL. The size of cysts before the first PT ranged from 55 to 154 mm (median 107; IQR 86.25–125.5): 11 (68.8%) were > 10 cm, whereas 5 (31.2%) were between 5 and 10 cm. Eight percutaneous aspiration and 10 catheterization procedures with drainage through insertion of a permanent catheter were performed. In case of catheterization, the catheter was left in place for a median of 13.5 days (IQR 1.75–48.5). The duration of catheterization was affected by occlusion in three cases and spontaneous displacement out of the insertion point in two cases. The details of the interventions are summarized in Table 2.

Table 2

Type of percutaneous treatment and association with ABZ

Patient progressive numberNo. of proceduresType of procedureDuration of Cat (days)Duration of ABZ pre- first puncture (months)Time interval from last ABZ intake and first puncture (months)Duration of ABZ post- first puncture (months)Time elapsed between procedures (months)Duration of ABZ post second puncture (months)HCF status (1 = viable; 0 = not viable)
12AspCat60126110310
21Cat5016610
31Cat154020
42CatCat2*122017300
52CatAsp715010111
61Asp3011
71Cat220181
81Cat1*061
91Cat1*3091
101Asp0101
111§Asp21169§1
121Asp061
131Asp0.5061
141Asp702261
151Cat484010

Cat = catheterization; Asp = aspiration; ABZ = albendazole; HCF = hydatid cyst fluid. “–” indicates that the event did not occur.

Occlusion of the catheter.

Spontaneous removal of the catheter.

Patient 7 underwent puncture of a second cyst not indicated in the table because the follow-up was shorter than 6 months (the second cyst was removed surgically after its rupture).

Patient 11 underwent a second percutaneous treatment of a second cyst that had to be interrupted for the onset of a major anaphylactic reaction.

Patient 12 underwent a second percutaneous treatment of the same cyst that had to be interrupted for the onset of rash and intense pain.

Eleven subjects (73.3%) had received ABZ treatment before the percutaneous procedure (Table 2 and Figure 5). In these patients, the duration of ABZ intake before the first puncture ranged from 15 days to 16 months (median 4 months; IQR 2–12). This wide range derives from the absence of a standardized protocol when the procedure was introduced. On microscopical analysis of the aspirated cyst fluid, the cyst was found viable in 13 procedures (72.2%; 8 of which being preceded by ABZ intake) and nonviable in five procedures (27.8%, all preceded by ABZ intake). After the puncture, all patients started or continued treatment with ABZ (Figure 5) for a minimum of 1 month (median 6; IQR 2–9).

Figure 5.
Figure 5.

Duration in months of ABZ course before and after puncture. White bars represent the duration of ABZ course before the first puncture. Gray bars represent duration of ABZ course after the first puncture. Black bars represent duration of ABZ course after the second puncture. Black stars indicate the time of first cyst solidification after the first puncture. White star indicates the time of second cyst solidification after the first puncture. Patient 13 had a 2-month pre-puncture ABZ course 116 months before the puncture. Note the scale divergence compared with the rest of the chart and indicated by the black stripes inside the white bar.

Citation: The American Journal of Tropical Medicine and Hygiene 97, 6; 10.4269/ajtmh.17-0468

The outcome and follow-up of patients and cysts included in the effectiveness study are summarized in Table 3. The follow-up of the 16 punctured cysts had duration of minimum 7 months, up to a maximum of 75 months (median 31; IQR: 21.25–52.25). At last follow-up, 10 cysts (62.5%) had reached solidification (stage CE4) (Figure 6). Time to solidification ranged from 3 to 69 months (median 12; IQR 5–31). Three cysts (18.8%) remained in the same stage but reduced their size (CE3a<), one cyst (6.2%) maintained the same stage (CE3a) and size. Two cysts (12.5%) reactivated (CE3b). In both patients, the CE3b cysts maintained this stage until the last follow-up.

Table 3

Cyst evolution during the follow-up

Patient progressive numberNo. of proceduresF-U after puncture (months)Stage at last F-UTime to solidification (months after puncture)Number of complicationsNumber of reactivationsTime to complications onset or reactivation (months after puncture)Size at last F-U (mm)
123828CE3a<1*17590
2141CE4558
3130CE43104
425750CE42269
523131CE3a<CE4316754
617CE3a113
7125CE4916
8156CE43877
9120CE41273
10110CE3a<43
11140CE3b101§2469
12175CE441151
13131CE41854
14110Ce3b1#4120
15169CE46988

FU = follow-up; “CE3a<” = CE3a stage with smaller diameter than pre-puncture. Gray boxes highlight the data regarding the second procedure of a single cyst that underwent two percutaneous procedures.

Patient 1 developed a communication with a biliary vessel after reaching an apparent solidification.

Patient 7 underwent puncture of a second cyst not indicated in the table because the follow-up was shorter than 6 months (second cyst was removed surgically after its rupture).

Patient 11 underwent a second percutaneous treatment of a second cyst that had to be interrupted for the onset of a major anaphylactic reaction.

In patient 11, the CE1 pelvic cyst reached solidification in 22 months after aspiration, then 2 months later the same cyst presented daughter vesicles in a solid matrix, characteristic of a stage CE3b.

Patient 12 underwent a second percutaneous treatment on the same cyst that had to be interrupted for the onset of rash and intense pain.

Patient 12 had a superinfection of the punctured cyst (1 month after aspiration).

In patient 14 the punctured cyst, after 4 month from the procedure, presented daughter vesicles in a solid matrix, characteristic of a stage CE3b.

Figure 6.
Figure 6.

Cumulative percentage of punctured cysts reaching the CE4 stage. Black dots represent the end of follow-up of cysts.

Citation: The American Journal of Tropical Medicine and Hygiene 97, 6; 10.4269/ajtmh.17-0468

We recorded two different types of complications: procedural complications, occurring perioperatively during the percutaneous treatment or the following hours, and follow-up complications, occurring months after the last percutaneous treatment (Table 4). Follow-up complications occurred in three patients (20%), and their time of onset ranged from a minimum of 1 to a maximum of 27 months after the first procedure. Procedural complications occurred only in two patients (13.3%) included in our PT effectiveness evaluation cohort. If we consider all procedural complications, including those that occurred in our effectiveness cohort patients (N = 15) and in those patients (N = 10) not included in the cohort due to a follow-up < 6 months, 3 out of 25 patients (12%) experienced procedural complications. No patient had to stop ABZ intake due to toxicity.

Table 4

Procedural and follow-up complications occurred in patients who underwent PT without injection of scolicidal agent, independently of length of follow-up

Progressive number of patients experiencing complications after the procedureNumber of procedures (included in the evaluation of procedure’s safety)Time elapsed between procedures (months)Stage before last procedureStage at last F-UNumber of complicationsType of complicationTime to complication (months after procedure)
1210CE3aCE3a1Follow-up*175
7221CE4CE3aCE4Surgical residue1Follw-up243
1122CE3aCE1CE3bCE41Procedural§0
1221CE3aCE42Follow-up1
Procedural10
16**1CE1CE1CE1CE3aCE3aCE3a1Procedural#0

Gray boxes highlight the data regarding the second procedure of a single cyst that underwent two percutaneous procedures. F-U = follow-up.

Patient 1 developed a communication with the biliary tree after reaching an apparent solidification (5 months after the second procedure, 17 months after the first procedure).

In the patients having more than one cyst undergoing puncture, the asterisk indicates which cysts developed complications.

Patient 7 experienced rupture of the cyst and therefore underwent pericystectomy (3 months after the second procedure, 24 months after the first procedure).

Patient 11 underwent a second percutaneous treatment that had to be interrupted for the onset of a major anaphylactic reaction that required the intervention of the anesthesiology specialist present in the room.

Patient 12 had a superinfection of the punctured cyst (1 month after aspiration).

Patient 12 underwent a second percutaneous treatment of the same cyst that had to be interrupted for the onset of rash and intense pain (minor anaphylactic reaction).

Patient 16 developed intense flank pain 1 hour after the procedure; an US examination evidenced leaking of the intracystic fluid inside the peritoneal cavity.

Patient 16 had a follow-up < 6 months, so it was not included in the cohort examined for effectiveness of the PT procedure.

DISCUSSION

This is the first study preliminarily evaluating the safety and effectiveness of the percutaneous treatment of unilocular abdominal CE cysts in the absence of injection of a scolicidal agent, with the adjunct of ABZ therapy instead of just prophylaxis. Notwithstanding the absence of a control group in our retrospective study, analyzing data from clinical routine procedures, the preliminary results of our observational study are overall comparable with those reported in the literature for other PTs, both in terms of response rate (72–97%), relapse rate (1.6–15%), and morbidity (8.5–32%),1629,3337 and support the hypothesis that the combination of PT and ABZ full course treatment may replace PAIR plus ABZ prophylaxis.

The limitations of this study include the retrospective design, the small number of patients, and their heterogeneity in terms of cysts localization and size, duration of ABZ course(s), intake before and/or after the procedure, and number of procedures. This heterogeneity derives both from the use of data obtained from routine practice (as opposed to clinical trial setting with a fixed protocol and a control group), and from the very diverse clinical histories of patients seen in our center, often referred after other therapeutic approaches were made in other hospitals. However, overall the results of this retrospective preliminary assessment of this modified PT omitting the injection of a scolicidal agent are promising in terms of safety and effectiveness.

Further larger prospective randomized studies would be warranted to properly evaluate the effectiveness of this procedure on all cysts eligible for PT and therefore benefitting from a shorter procedure and omission of introduction of an histolesive agent, using a standard protocol, with ABZ administered only after the procedure and started a few hours/days before it, and appropriate control groups (classic PAIR arm and ABZ only treatment arm). The rational of this ideal approach is based on the observation that ABZ is more effective in the treatment of small cysts and that likely part of the failure of ABZ therapy is due to the erratic intracystic concentration reached by the molecule, also diluted in variable volumes of hydatid fluid.38,39 Thus, ABZ therapy would likely have increased effectiveness when hydatid fluid was simply removed from the cyst, adding to the disruption of the cyst wall induced by the puncture. Different ABZ treatment durations should be also evaluated, as it is possible that a treatment course shorter than the suggested 6 months may be equally effective. This would be beneficial, on the one hand, to reduce the risk of ABZ toxicity, although this is generally manifested early during intake and none of our patients had to stop treatment due to ABZ toxicity. On the other hand, shortening the course of treatment would be very important to reduce the cost of ABZ treatment, a problem especially experienced in low income countries and/or where the full cost of treatment needs to be borne by the patients.

Acknowledgment:

We are grateful to Sam Goblirsch, MD, for editing the English.

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Author Notes

Address correspondence to Francesca Tamarozzi, Center for Tropical Diseases, Sacro Cuore Hospital, Don A Sempreboni 5, 37024 Negrar, Verona, Italy and WHO Collaborating Center for Clinical management of Cystic Echinococcosis, Via Taramelli 5, 27100 Pavia, Italy. E-mail: f_tamarozzi@yahoo.com

Financial support: This study was funded through the European Union Seventh Framework Programme (FP7/2007–2013) under the project HERACLES, grant agreement no. [602051].

Authors’ addresses: Giovanni Firpo, WHO-Collaborating Centre for Clinical Management of Cystic Echinococcosis, Pavia, Italy, E-mail: giovanni.firpo01@universitadipavia.it. Ambra Vola and Raffaella Lissandrin, WHO-Collaborating Centre for Clinical Management of Cystic Echinococcosis, Pavia, Italy, and Division of Infectious Tropical Diseases, San Matteo Hospital Foundation, Pavia, Italy, E-mails: ambra.vola@gmail.com and raffaella.lissandrin@unipv.it. Francesca Tamarozzi, Center for Tropical Diseases, Sacro Cuore Hospital, Negrar, verona, Italy, and WHO Collaborating Center for Clinical Management of Cystic Echinococcosis, Pavia, Italy, E-mail: f_tamarozzi@yahoo.com. Enrico Brunetti, WHO-Collaborating Centre for Clinical Management of Cystic Echinococcosis, Pavia, Italy, Division of Infectious Tropical Diseases, San Matteo Hospital Foundation, Pavia, Italy, and Department of Clinical, Surgical, Diagnostic and Paediatric Science, University of Pavia, Pavia, Italy, E-mail: enrico.brunetti@unipv.it.

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