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Human hydatid disease or cystic echinococcosis, caused by the larval form of cestode
Echinococcus granulosus, still continues to be a common health problem in most sheep
rearing regions of the Asia, Europe, the Mediterranean, South America, Australia and New
Zealand. The liver is the most frequently parasitized organ in humans with about 60% infestation
rate and with 75% of cysts being located in the right lobe.[1,2]
Until three decades ago, surgery was the only treatment option available for liver hydatid
cysts (LHCs). However, surgery is not possible if the cyst is located centrally in the liver or in
contiguity with vascular structures. Surgery, the oldest and still most common treatment
employed for LHCs carries a definite risk of morbidity and mortality. Also, the recurrence of
more than 10% is a bigger concern associated with surgery. The figures of morbidity, mortality
and recurrence further increase in patients with multiple cysts, disseminated disease or recurrent
disease. Also, patients with cardiac, respiratory, renal or neurologic co-morbidities who carry
high risk for general anesthesia are not good candidates for surgery.[3,4,5] Therefore, an effective
and safe alternative treatment modality will be highly desirable.
During the last three decades, two alternative forms of therapy for LHCs have evolved;
systemic chemotherapy and percutaneous drainage (PD). Mebendazole was the initial
chemotherapeutic agent but has limited use due to its poor efficacy. Mebendazole has been
largely replaced with albendazole which is well absorbed unlike the former compound. Although
the success rate of the systemic chemotherapy varies with the type of cyst, clinical experience
indicates that about one-third of the patients are cured with such treatment. Chemotherapy
achieves a cyst disappearance rate of 30%, partial response in another 30% and no response
in 40%. It is effective in small cysts (<4 cm diameter), cysts with thin walls and in younger
patients. It is indicated in patients who are high risks for surgery, in patients with multiple
peritoneal cysts, disseminated systemic disease, to prevent secondary echinococcosis after
spillage during surgery, and in combination with PD. Imidazoles cause hepatic and hematologic
toxicities and are potentially embryotoxic and teratogenic.[6,7,8,9]
The third option for treatment of hydatid cysts in the liver and some other locations is the
PAIR procedure wherein “P” stands for percutaneous puncture of the cyst under sonographic
guidance; “A” stands for aspiration of substantial amount of the cyst contents; “I” stands
for injection of proctoscolicidal agent (e.g. hypertonic saline, 95% ethanol, albendazole or
betadine), and “R” for reaspiration. Recent experiences on PAIRs in thousands of patients
from different parts of the world have documented excellent results in terms of efficacy, safety
and cost-effectiveness.10,11,12The long-term results are equally satisfactory.[13,14,15,16,17,18]Other advantages
include requirement for minimal infrastructure and can be performed in remote resource poor regions where echinococcosis is endemic.
PD of LHCs has been contraindicated for risk of anaphylactic
shock and spillage and seeding of scolices resulting in
peritoneal implantation and dissemination. These long-held
concerns have been challenged by many studies with PAIR.
Anaphylaxis is a very rare complication of PAIR procedure.
Likewise, rupture and spillage during PAIR procedure is rare
because of use of improved imaging, fine needles and catheters and the right intercostal transhepatic route for puncture.[10,11,12,13,14,15,16,17,18]
Randomized controlled[19]as well as uncontrolled studies have shown superiority of PAIR over surgery in terms of shorter hospital stay, complications and cost-effectiveness.[20,21,22]On the basis of positive short-term and long-term results World Health Organization (WHO) recommended PAIR approach for management of uncomplicated LHCs in selected cases.[23]Although, in most reported studies PAIR technique was highly efficient and safe for uncomplicated unilocular cyst (Gharbi type 1 or WHO CE1) and unilocular cyst with ruptured laminated membranes (Gharbi type 2 or WHO CE3a), but many authors experienced problems regarding efficacy and safety with PAIR in patients with multivesicular cysts with minimal (Gharbi type 3 or WHO type CE2) or predominant non-drainable
contents (Gharbi type 3 or WHO type CE3b). Some authors
reported high failure rate of upto 30% in PAIR of multivesicular
cysts.[20,24]For effective treatment of such LHCs each daughter cyst has to be punctured separately which is laborious and inconvenient for the patient. The aim in surgical treatment is to inactivate the parasite, evacuate the cyst cavity, remove the germinal membrane and obliterate the residual cyst cavity. The aim of percutaneous treatment is the same except for removal of the germinal layer. A number of modified percutaneous techniques have been developed to address some of the shortcomings of PAIR to effectively and safely treat multivesicular cysts. Saremi et al[25]described a percutaneous approach in which a special cutting instrument is used to fragment and evacuate daughter cysts and laminated membrane while the cavity is continuously irrigated with scolicidals. Their described technique is similar to surgery. Aspiration of both
fluid and solid contents including the membranes facilitates the anti-parasitic effect of scolicidals more effectively. The wide bore of the instrument permits effective percutaneous removal of all hydatid contents. Schipper et al[26]described a percutaneous evacuation of cyst contents (PEVAC) using a large bore catheter after dilatation of the tract over two sessions. The article in this issue of the journal[27] describes a technique almost similar to those described by Schipper et al and Haddad et al.[26,28] These modified PAIR procedures are interesting and encouraging for the treatment of types CE2 and CE3b LHCs (type 3 Gharbi cysts) but suffer from flaws of
including small number of patients and short follow-up.
In presence of availability of three treatment options, it remains an open question as to whether PAIR can be used as the first line of therapy for LHCs. A non-operative therapy always carries potential economic and societal advantages. Smego et al[21]conducted a meta-analysis across 21studies comprising of 769 patients with 1,072 hepatic cysts undergoing PAIR plus albendazole therapy and compared the findings with 952 era-matched controls treated with surgery. They found that PAIR plus chemotherapy is associated with significantly greater clinical and parasitological efficacy; lower rates of morbidity, mortality and disease recurrence; and shorter hospital stay (2.4 days vs. 15 days).[21]Such results are interesting but suffer from the same flaws (small series, retrospective, short follow-up, etc). Dziri et al[29] attempted to address the role of chemotherapy, surgery and/or PAIR for LHCs and concluded that PD plus albendazole resulted in safe and efficient treatment for selected patients. A Cochrane data systemic review in 2006 assessed the benefits and harms of PAIR with or without benzimidazole coverage for patients with uncomplicated hepatic hydatid cyst in comparison with sham/no intervention, surgery or medical treatment.[23] The authors identified only two randomised clinical trials, one comparing PAIR versus surgical treatment[19] and the other comparing PAIR (with or without albendazole) versus albendazole alone.[8] They concluded that PAIR seems promising, but there is insufficient evidence to support or refute PAIR with or without benzimidazole coverage for treating patients with uncomplicated hepatic hydatid cyst and suggested need to undertake well-designed randomised clinical trials to address this issue. Kabaalioglu et al[20] in 2006 concluded that PAIR is safe and effective for LHCs of types I and II and surgery should be reserved for type III and certain active type IV cysts. A recent paper from Turkey reported a single-center experience comparing surgery, laparoscopic surgery, and percutaneous treatments in 355 patients over a period of 10 years and concluded that PAIR is an effective and safe option.[22] On the basis of current evidence PAIR procedure is a safe and efficient option for uncomplicated LHCs of types I and II by Gharbi classification or CE1 and CE3a (WHO-IWGE classification) but the evidence for type III (Gharbi) or CE2 and CE3b (WHO classification) multivesicular cysts with slight or significant non-drainable contents in favour of modified techniques of PAIR is encouraging but not well-established. Since the time of appearance of recurrence is quite variable, it has been suggested to continue monitoring for extended period of 5 years or more before it can be said that patient has no recurrence. Finally, the choice between modified PAIR and surgery will be dictated by local expertise.
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