Hydatid disease is a zoonotic infection caused by larval forms of Echinococcus granulosus and is endemic in the Mediterranean area, Middle East, South America, India, northern China and Australia. Cystic hydatid disease usually affects the liver (50–70%) and less frequently the lung, spleen, kidney, bone, and brain.[1] Hepatic echinococcal cysts generally remain asymptomatic until their expanding size or their spaceoccupying effect result in symptoms. Most common presentation is abdominal pain or a palpable mass in the right upper quadrant. Rupture of or episodic leakage from a hydatid cyst may produce fever, pruritis, urticaria, eosinophilia, or anaphylaxis. Infection of the cyst can facilitate the development of liver abscesses and mechanical local complications such as mass effect on bile ducts and vessels that can induce cholestasis, portal hypertension and Budd-Chiari syndrome.[2, 3] In addition, the presence of daughter cysts in an older cyst represents a significant risk of recurrence after surgery. Therefore, treatment of liver hydatid cysts is considered mandatory in symptomatic cysts and is recommended in viable cysts because of the risk of severe complications.[1]

Treatment of hepatic hydatid is based on ultrasound staging and considerations of the size, location and manifestations of cysts, and the overall health of the patient. There are several classification schemes for liver hydatid cysts based on their ultrasound appearance; the initial classification by Gharbi et al and the WHO Informal Working Group on Echinococcosis (IWGE) classification are the most commonly preferred.[4] Hassen Gharbi classified hepatic hydatid into five types based on sonographic appearance.[5] WHO classification is almost the same as Gharbi’s, with Gharbi type II corresponding to CE 3A of the WHO classification, and vice versa. However, there are two important additions in the WHO classification: the predominantly solid cyst with daughter cysts, which was not explicitly included in Gharbi’s classification, has found a place in the CE 3 slot, and the types are now grouped according to their biological activity (Table 1). This has important consequences for treatment decisions.[6]

For many years surgery was the only available treatment for hepatic hydatid cysts and was associated with high morbidity, mortality, and relapse rates of 32%, 8%, and 20%, respectively.[6] The failure rate for medical management of hydatid cysts with benzimidazole compounds (i.e., albendazole and mebendazole) used alone approaches 25%, with most cases of relapse occurring within 2 years of cessation of therapy.[7] In recent years percutaneous, minimally, invasive treatment of hepatic hydatid cysts has developed into an attractive alternative to surgery and benzimidazole derivatives for certain cyst stages.[6] It has been tried with considerable success in types I and II, with encouraging long term results.[8] However reports on percutaneous treatment of type III cysts are limited. At our institution surgery is still the mainstay of treatment of Gharbi type III. We are presenting our experience with treating these patients using minimally invasive techniques in a select group of patients who refused surgery.

Methods

From March 1994 to November 2007, 11 patients with 13 Gharbi type III (WHO type CE 2 and CE 3B) hepatic hydatid cysts were enrolled for our study. This study was conducted in Department of Radiodiagnosis, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow (UP), India. There were 6 female and 5 male patients; age ranging from 32 – 67 yrs (mean age 43 yrs). The chief presenting complaints were right upper quadrant (RUQ) pain (n = 9), RUQ mass (n = 7), and epigastric discomfort (n = 8). In 2 patients the cysts were incidentally detected during imaging for unrelated complaints. No patient had prior surgical intervention. The diagnosis of heterogeneous hepatic hydatid cysts was based on characteristic cyst morphology on cross sectional imaging, ultrasonography (USG) (Figure 1) and computerized tomography (CT) (Figure 2) and indirect hemagglutination (IHA) test. All heterogeneous hepatic hydatid cysts were located in the right lobe. The average cyst diameter was 9.6 cms (range 5 -13 cms). All type I and II hydatid cysts referred to our department during this period, were treated with puncture, aspiration, injection and re-aspiration (PAIR) technique and were not included in this study. At each follow up a through clinical examination and abdominal ultrasonography was performed. All ultrasonographic examinations were evaluated by two authors (SSB and SM). The diameter and echo pattern of the cysts were documented. In addition, the liver, biliary tree, and other abdominal organs were carefully examined for evidence of residual or recurrent cysts.

Technique

Written informed consent was obtained and detailed technique, other available modes of treatment, and complication rates were explained to all the patients. The patients were subjected to USG examination before the procedure. All patients received oral albendazole 10mg /kg body weight, starting four week pre-procedure and continuing for 4 weeks after the procedure. After overnight fast an IV line was secured and 100 mg of hydrocortisone and 50 mg of diphenhydramine were given 20 minutes before the procedure. The procedure was performed in the intervention suite under combined fluoroscopy and ultrasound guidance, under local anesthesia and moderate sedation. An anesthesiologist was always available to manage potential anaphylaxis.

The cyst was punctured under sonographic guidance with an 18 G needle. Longest available tract between the liver capsule and the cyst wall was chosen as the site of puncture. The cyst aspirate where obtained (n=7) was sent for microbiological analysis for the presence of scolex and its mobility. A 0.035 super stiff guide wire (Cook, Bloomington Inc, USA) was inserted into the cyst and the tract was sequentially dilated to 18 - 24 French. A large bore sheath (Amplatz Renal introducer set, Cook Bloomington Inc, USA) was subsequently inserted and stabilized manually. A suction catheter of 14 Fr size was passed through it and the cyst contents were actively sucked mechanically, using a suction apparatus. The catheter was directed in different quadrants of cysts for effective removal. Complete evacuation of solid portions (pearly white grapelike membranes) (Figure 3) was attempted at the initial stage in all patients. After satisfactory removal, the suction catheter was withdrawn, retaining the large bore catheter. A cystogram was then performed to look for any residual solid elements and to demonstrate any biliary ductal communication. If more solid elements were seen (Figure 4a), the suction procedure was repeated until the clearance of cavity (Figure 4b). After achieving cyst unilocularity, the large bore sheath was exchanged with a 16 Fr to 20 Fr large bore catheter, which was connected to a bag for drainage. The 48 hour drain output from these catheters was sent for estimation of bile salts to reconfirm lack of any possibility of biliary ductal communication. Absolute alcohol, used as a scolicidal agent, was then instilled in the cyst cavity, which was re-aspirated after 20 minutes. Volume of absolute alcohol to be injected was taken as 50% of the drain output in last 24 hours. The patients were discharged 48 hours later, after downsizing the catheter to 12-14 Fr. In one patient who had 3 hydatid cysts, a two stage procedure was performed, where two cysts were addressed in first, and the third in the second session. No scolicidal/ sclerosing agent was instilled in three patients who demonstrated biliary ductal communication on repeat cystogram.

Follow up serial ultrasound and drainage pattern of cysts were evaluated on outpatient visits every 7-10 days. When the cyst aspirate decreased to <10 ml per 24 hours the catheter was removed. In cases, where the cyst drainage fluid was bile stained or the catheter output was persistently higher, the catheter was retained for longer periods till spontaneous decrease in output was encountered. In one patient there was persistent output, even after 32 days, in whom endoscopic retrograde cholangiography (ERCP) was performed and a plastic stent was placed.

After catheter removal, follow-up sonogram was performed at 1, 3, 6 and 12 months and every year thereafter. Decrease in cyst size, progressive solidification, formation of a pseudotumour or complete disappearance were regarded as positive signs of response.

Results

The results are summarized in Table 2. The cysts were completely evacuated in all patients. All patients tolerated the procedure well, with no anaphylaxis. On microscopy, cyst aspirate (obtained in n=7 patients) showed presence of laminated membranes and protoscolices confirming that these cysts were active. Cystogram immediately after the procedure did not show any biliary ductal communication. However in 3 patients bilio-cystic communication was noted 48 hours later. Spontaneous reduction in drain output was noted in 10 patients. In 1 patient when the output did not reduce after 32 days, ERCP with papillotomy and stenting was performed.

Subsequently this patient also showed diminished drain output. Mean duration of catheter placement was 11.3 days (range 7 to 40 days). In uncomplicated patients (n = 8) the average duration of hospital stay was 3 days (range 1 to 4 days). In patients with bilio-cystic communication (n = 3) mean hospital stay was 4 days (range 3 to 6 days). Minor complications were encountered in 7 patients in the form of urticaria (n = 3), reactive pleural effusions (n = 3), pain (n = 6), and fever (n = 2). All patients responded to symptomatic treatment. Follow up serial ultrasound was performed on all patients. After percutaneous treatment, the cysts gradually underwent a sequence of sonographic changes from appearance of high-level internal echoes (a heterogeneous pattern), obliteration by echogenic material (a pseudotumor pattern), decreased echogenicity, and finally a normal pattern of echoes. The cyst was considered to have disappeared if it was no longer visualized on ultrasonography and the area was replaced by an ill-defined echogenic area or a normal echo pattern. Complete healing was seen in 9 patients and formation of so called pseudotumour in 4 patients. The mean follow up was 15.23 months (6 months – 2 years).

Discussion

Percutaneous treatment of hepatic hydatidosis, initially introduced in the mid-1980s, has developed into an attractive alternative to surgery and benzimidazole derivatives for certain cyst stages.[3,9] This treatment modality for hepatic hydatidosis destroys the germinal layer with scolicidal agents or evacuates the entire endocyst.[6] It has been tried with considerable success, especially for the unilocular hepatic hydatid cysts, with encouraging long term results.8,10,11,12,13,14 The first successful percutaneous drainage of hepatic hydatid cyst was reported by Mueller el al in 1985.[9] They drained the cyst percutaneously under imaging guidance and then lavaged the cavity through a catheter using silver nitrate and hypertonic saline solutions. All liver function tests remained normal on one year follow up.

Subsequently in 1990, a new therapeutic approach involved the following steps: puncture the cyst, aspirate cyst fluid, inject a scolicidal agent, and re-aspirate the cyst content (PAIR).[10,11] Giorgio et al and Kabaalioglu et al reported repeated failures of PAIR in multivesiculated cysts or cysts with predominantly solid contents and daughter cysts, Gharbi type III (CE2 and CE3B), possibly attributable to difficulty in extracting solid components and cyst membranes.[15,16] Giorgio et al showed that PAIR of multivesiculated cysts does not allow complete healing and in 30% of cases resulted in an intracystic recurrence that required up to four repeat procedures.[15,16] These findings prompted most clinicians to use PAIR exclusively for unilocular cysts, with or without detached endocysts. For this reason Gharbi type III cysts are now preferably treated with other percutaneous techniques based on the aspiration of the “solid” content of the cyst, the germinal and the laminated layer, through a large-bore catheter or device.[6] Two types of approaches are currently in use: the catheterization technique[17] and the modified catheterization techniques, in particular PEVAC (percutaneous evacuation), MoCaT (modified catheterization technique), and DMFT (dilatable multi-function trocar).[6] Haddad et al used large-bore 14 Fr van Sonnenberg sump catheters for drainage and suction of membranes in type IV cysts.[18] We used larger 24 Fr bore catheter to achieve the same. This along with wide distal end holes and val large side holes offered better extraction of the solid cyst contents. We found this to offer significant advantage for sufficient evacuation of solid elements.

A large-bore cutting-aspiration device was used by Saremi and McNamara in 32 patients to fragment and evacuate daughter cysts and the laminated membrane.[19] A 2-year followup showed a high rate of success (90%) and a low incidence of major complications (3%). Vuitton et al treated 699 multivesiculated abdominal cysts with a device called DMFT which was linked to an aspiration apparatus to extract the endocyst, daughter cysts and other cystic contents.[20] Thereafter, the cavity was irrigated with 10–20% saline and if necessary curettage was performed. The catheter remained in the cavity for 2–3 days. No deaths but four anaphylactic reactions were observed in their series. The recurrence rate in a 3-year follow-up was 2.3% in-situ and 1% in other locations. Schipper et al treated 12 patients with unilocular and multivesiculated cysts, including complicated ones with PEVAC.[21] Aspiration and evacuation of cyst content were performed with a 14 Fr catheter. Cysto-biliary fistulas were treated with an endoprosthesis introduced endoscopically into the common bile duct. In a mean period of 17.9 months (range 4 – 30 months) seven cysts disappeared and five decreased in size. The main complications of this procedure were caused by cysto-biliary fistulas and secondary infections. These complications prolonged hospitalization from 11.5 (range 8–14 days) to 72.3 days (range 28–128 days).

Giorgio et al in their study proved efficacy of double percutaneous aspiration and ethanol injection for previously untreated patients with viable univesicular and multivesicular hydatid liver cysts not only in the short term, but also over long term and showed that this technique has a lower cost, shorter hospital stay and fewer recurrences.1 We also used absolute alcohol as scolicidal agent in hepatic hydatid cysts which did not have any biliary ductal communication.

As compared to the available literature, results of our study were better with mean duration of catheter placement being 11.3 days (range 7 to 40 days). Number of days of hospitalization was only 3 days in uncomplicated patients (n = 8). In patients with bilio-cystic communication (n = 3) mean hospital stay was 4 days (range 3 to 6 days). Complete healing was seen in 9 patients and formation of so called pseudotumour in 4 patients, which was chosen as end point of our study, thus showing a 100% success rate with a mean follow up of 15.23 months and no recurrence.

The major risks of percutaneous techniques are anaphylactic shock, secondary echinococcosis caused by spillage of cystic fluid and chemical cholangitis caused by contact of the scolicidal agent with the biliary tree. It is imperative to have resuscitation measures in place, to choose a safe approach to the cyst, to give peri-interventional prophylaxis with benzimidazoles and to exclude communications with the biliary tree before injection of any scolicidal agent.[6]

To avoid potential spillage we chose the longest available tract between the liver capsule and the cyst wall as the site of puncture. Thus the liver parenchyma can have a sealing effect against the inadvertent spillage during the procedure (tamponade effect). We ensured that all safety measures were in place by giving 100 mg of hydrocortisone and 50 mg of diphenhydramine 20 minutes before the procedure. The procedure was performed under local anaesthesia but an anesthesiologist was always available during the procedure to manage potential anaphylaxis. No serious complications, anaphylaxis or deaths were encountered in our series. Minor complications such as urticaria, fever and reactive pleural effusion were encountered in 7 patients who responded to symptomatic treatment. However three patients showed a minor complication of biliary fistula which was managed by retaining catheter for longer periods of time in 2 patients until the spontaneous output reduced to <10cc/ day and by endoscopic retrograde cholangiography (ERCP) with plastic stent placement in 1 patient.

Prophylactic albendazole therapy was used in our study with two considerations. First, in animal studies it has been reported that albendazole therapy offers protective effect against pro-spillage.[22] Khuroo et al in a prospective randomized controlled study have shown that prophylactic albendazole therapy prior to percutaneous treatment has better results as compared with percutaneous treatment or albendazole therapy alone.[23]

Thus we conclude that percutaneous treatment is a safe and effective alternative therapy in treating Gharbi type III hepatic hydatid cysts for patients who refuse surgery and require a shorter hospital stay.

References