Laparoscopic aspiration and excision versus double percutaneous aspiration, ethanol injection and re-aspiration for treatment of viable univesicular hydatid liver cysts

Laparoscopic aspiration and excision versus double percutaneous aspiration, ethanol injection and re-aspiration for treatment of viable univesicular hydatid liver cysts

Samy Saad,a MD; Alaa El-Ashry,a FRCS; A Meccawy,b FRCS;

Osama Murshed,c FRCS; Khaled A Ahmad,c MD; Ahmed Farouk, d MD

a) Department of Genaral Surgery, Ain Shams University, Cairo, Egypt. b) King Abdulaziz University, KSA.

c) King Fahd Hospital, KSA.

d) Department of Radiology, Ain Shams University, Cairo, Egypt.

Abstract

Aim of work: The purpose of this study is to compare the efficacy of double percutaneous aspiration and ethanol injection, with laparoscopic aspiration and  excision in patients with viable univesicular hydatid liver cysts.

Patients & methods: The study was done over 30 patients divided randomly into 2 groups : Group I (n=15): Patients presented with a univesicular hydatid cyst and treated with ultrasonography - guided double per-cutaneous aspiration and ethanol injection. Group II (n=15): Patients presented with a univesicular hydatid cyst and treated with laparoscopic aspiration and excision. All patients were diagnosed primarily by ultrasonography then confirmed by CT scan and hematological screen on the basis of the presence of antibodies against Echinococcus granulosus using enzyme-linked immunosorbent assay (ELISA) at a titer of •

1:128. Patients with multivesicular hydatid liver cysts, recurrent cases, patients with chronic liver diseases and patients with non-parasitic liver cystic lesions are excluded from the study.

Results: The mean operative time and hospital stay were significantly short in group I. There was no mortality in both groups. Intra-cystic bleeding was observed  in 1 (6.7%) patient in group I and was referred for surgery. Bile leak occurred in 2 (13.3%) patients in group II. Cavity infection with abscess formation occurred in 2 (14.3%) patients in group I. No major complications occurred in both groups apart from minimal pleural effusion in 1 (6.7%) patient in group II. No local recurrence was observed in follow up of group II patients compared to 2 (14.3%) cases of recurrence in group I. The cysts disappeared in 9 (64.3%) patients in group I with reconstruction of liver parenchyma while group II showed cyst disappearance in all (100%) patients of the group.

Conclusion: Laparoscopic management of hydatid hepatic cysts (HHC) seems effective and safe, with low morbidity and recurrence rates. Double percutaneous aspiration and ethanol injection showed high efficacy on unilocular hydatid hepatic cysts in terms of disappearance of the cysts and few side effects and can be considered a first line in treatment of unilocular non-complicated hydatid liver cyst.

Introduction:

Hydatid disease, due to the larval form of a tapeworm Echinococcus granulosus, is a parasitic disease endemic in the Mediterranean area, Middle East, South America, India, Northern China, and Australia.1

Cystic hydatid disease usually affects the liver (50-70%) and less frequently lung, spleen,

kidney, bone, and brain.2 Liver hydatidosis can cause dissemination or anaphylaxis after a cyst ruptures into the peritoneum or biliary tract. Infection of the cyst can facilitate the development of liver abscesses and mechanic local complications, such as mass effect on bile ducts and vessels that can induce cholestasis, portal hypertension, and Budd-

Chiari syndrome.3 In addition, the presence of daughter cysts in an older cyst represents a significant risk of recurrence after surgery.1

Treatment of hydatid liver cyst has to be considered mandatory in symptomatic cysts and recommended in viable cysts because of the risk of severe complications.3 In the last two decades, minimally invasive sonographically guided percutaneous approaches   have   been   developed. 4

Percutaneous aspiration, injection with scolicidal agents, and reaspiration (PAIR) have been widely used with excellent results.4,5

The main complication of PAIR is anaphylaxis because of spillage of the echinococci. However, many reports showed that anaphylaxis is a rare event when the procedure is performed by an expert operator.6,7

Laparoscopic management was first reported in 1991 by two separate groups; however, laparoscopy was used before this for diagnosis of hepatic cysts.8,9 The first use of diagnostic laparoscopy for hepatic cyst was documented in 1955.10 In fact, laparoscopic ultrasonography was used for diagnosis of liver disorders as early as 1989.11 Currently, laparoscopy plays a significant role in the management of primarily   sporadic   hepatic   cysts. 12

According to literature, laparoscopy, in comparison with the percutaneous technique, has many advantages, mainly the possibility of controlling the location of the cyst, protecting the surgical area from hydatid leaks, sterilization of the remaining walls and detection and treatment of possible biliary complications.13

Laparoscopic hydatid surgery follows the basic surgical principles of treating hydatid cysts of the liver: evacuation of the live cyst content, prevention of spillage and sterilization of the cavity with scolicidal agents.12,13

Patients and methods:

This randomized prospective observational study was conducted on thirty patients (24 males and 6 females), with ages ranging between 22 and 65 years, presented with univesicular hydatid cyst of the liver, in Ain Shams University Hospital (Egypt), Bugshan Hospital (Saudi Arabia), King Abdulaziz University Hospital (Saudi Arabia), King Fahd Hospital (Saudi Arabia) and Prince Abdulaziz

Bin Mosaed Hospital (Saudi Arabia) ; during the period between November 2001 until March

2009.

The patients were randomly divided into 2 groups using closed envelopes:

• Group I (n=15): Patients presented with a univesicular hydatid cyst and treated with ultrasonography - guided double per- cutaneous aspiration and ethanol injection and re-aspiration (PAIR).

• Group II (n=15): Patients presented with a univesicular hydatid cyst and treated with laparoscopic aspiration and excision.

All patients were diagnosed primarily by:

• Ultrasonography then confirmed by CT scan which also gave further information regarding the extent of the cyst and its proximity to any vital structures within the liver.

• Hematological screen on the basis of the presence           of   antibodies   against Echinococcus granulosus using enzyme- linked immunosorbent assay (ELISA) at a titer of • 1:128.

All patients underwent routine blood investigations, bleeding profile, chest x-ray and ECG. Informed written consent was obtained from all patients included in the study. Patients with multivesicular hydatid liver cysts, recurrent cases, patients with chronic liver diseases and patients with non-parasitic liver cystic lesions are excluded from the study. Laparoscopic Aspiration and Excision

• Preoperative

Mebendazole (3 g/d) was administered for

10 days before the operation.

• Ports

1. 10 mm camera port in the umbilicus or supra-umbilically, depending on the position of the cyst.

2. 10 mm right-hand working port in the patient's left upper quadrant, the exact site of which was determined by the size and location of the cyst.

3. 5 mm left-hand working port in the right upper quadrant.

4. 5 mm port in epigastrium or right hypochondrium   for   liver   retraction.

• Operative technique

The same basic rules of open surgery for liver  hydatid  were  followed.  After  the

introduction of the camera port, the cyst is identified. The right- and left-hand working ports are inserted under vision. Wet packs soaked with hypertonic saline were applied around the liver and the cyst Figure(1). A laparoscopic trocar-cannula is used to puncture and aspirate the fluid inside the cyst to confirm the absence of biliary staining and to replace the aspirated fluid with hypertonic saline solution which was kept inside the cyst for 20 minutes to destroy all parasitic cells by osmosis Figure(2). The pericystic cavity was opened using ultrasonic shear about    2 to 3 mm from the junction between the cyst and liver parenchyma Figure(3). The internal germinal membrane was then excised and put in an extraction bag together with most daughter vesicles and extracted out of the peritoneal cavity Figure(4). The cavity is then explored and any remnant daughter vesicles were carefully removed Figure(5), then, lavage of the cavity with hypertonic saline was done Figure(6). The cavity was then obliterated with omentopexy and drain is placed intra- abdominally for 24 - 48 hours in non- complicated cases Figure(7).

• Postoperative

Patients are typically discharged after 48-

72 hours in non-complicated cases. In cases of significant drain output, the patients were allowed to stay in the hospital for longer time or were discharged with the drain in situ, which is then removed on follow up. All patients received Mebendazole (3 g/d)  for 8 weeks postoperatively. The cyst size was monitored by US after two weeks and then at 1, 3, 6, 12 and in some cases at 24 months. If clinically indicated, US was repeated at shorter intervals. CT scan was performed if any complication is suspected. The primary end points were defined as complete cyst collapse by US at the end of the procedure, disappearance of cyst cavity or at least 50% reduction in cyst size at follow up imaging, and disappearance of complications such as pain, cystobiliary fistulas, vascular or biliary compression, and infection.

The secondary end points of the study were recurrence of cyst cavity to >50% of its initial size, vascular or biliary compression, development of fistulas, pain or infection within two years after surgery, death, withdrawal from the study, or loss to follow up.

Double percutaneous aspiration and ethanol injection and re-aspiration (PAIR) technique The procedure was always performed routinely under local infiltration anaesthesia with an anesthesiologist present for deep sedation without endotracheal intubation. Under sonographic guidance, the cyst was punctured using a 22-, 20-, or 18-gauge needle (Ecojekt, HS) according to the cystic volume. After aspirating as much fluid as possible, 95% sterile ethanol was injected into the cyst and left in situ for 20 minutes to replace 50-60% of the amount  drained.  At  least  1  cm  of  liver parenchyma was interposed between the liver surface and cystic wall, when possible. In case of a sub-capsular location, the needle was directly inserted into the cyst. Immediately after  the  aspiration  of  cystic  fluid,  a parasitologist searched for viable scolices with direct fresh microscopic examination and staining with 0.1% neutral red. Mebendazole (3 g/d) was administered 10 days before and

8 weeks after double percutaneous aspiration and   ethanol   injection   to   all   patients.

• Follow-up

All patients underwent sonographic examinations after 2 weeks then at 1, 3, 6, 12 and in some cases at 24 months Figure(8). Ultrasonography was performed to control the efficacy in terms of disappearance of the cysts with reconstitution of liver parenchyma, decreased fluid component and solid pattern appearance, or decreased volume of the cyst. The reappearance of single or multiple pure liquid cysts with well-defined walls within a previously completely treated cysts was considered to be local recurrence, and the relapsed cyst was treated again with double percutaneous aspiration and ethanol injection.

Figure(1): Wet packs soaked with hypertonic saline.

Figure(2): Trocar-cannula inside the cyst.

Figure(3): Cavity is opened by ultrasonic shear.    Figure(4): The cyst wall inside the extraction bag.

Figure(5): Removal of remnant daughter vesicles.

Figure(6): Lavage with hypertonic saline.

Figure(7): Omentopexy with intraperitoneal drain.

(A)                                  (B)                                 (C)                                (D)

Figure(8): A) Cyst before aspiration. B) 3 months after aspiration. C) 6 months after aspiration. D) 12 months after aspiration.

(A)                                               (B)

Figure(9): A) Cyst before aspiration.         B) Residual liquid components after aspiration.

In both groups,   ELISA titers were determined monthly during the first 6 months and then twice a year. Chest radiography was scheduled every 6 months to exclude lung localization, and a pelvi-abdominal CT was scheduled to exclude peritoneal and extraparenchymal localizations if needed.

Statistical Analysis

Data   processing   and   analysis   were

performed with Statistical Package of Social

Sciences version 11, (SPSS INC Chicago,III).

Results:

The study was conducted over 30 patients (24 males and 6 females). Their ages ranged from 22 to 65 years with the average age being

48.6 years. The clinical presentations of the patients of the study are summarized in Table(1).

Table (1): Clinical presentation of the patients.

All our patients had a single cyst classified as CE1 or CE3 according to WHO classification of hydatid cysts.14 Right-sided cysts   were   overwhelmingly   common,

constituting 23 of our patients, with only 7 patients having a cyst in the left lobe of the liver. WHO classification of hydatid cysts is shown in Table(2).

Table (2): WHO classification of hydatid cysts.

The diameter of the cysts ranged from 5.4 cm to 35.6 cm, with a median of 16.2 cm on ultrasonography. Mean diameter of the cyst in Group I was 20.3±15.3; while that recorded in Group II was 19.8±14.1; which were statistically  nonsignificant  (P>0.05). In Group I :

One course of double percutaneous aspiration and ethanol injection was performed in 12 patients (80%), two courses were performed in two patients (13.3%), while three courses were performed in one case (6.7%), with one very large univesicular hydatid liver cyst 35.6 cm.

One patient (6.7%) of the 15 patients of this group showed intra-cystic bleeding during the first needle aspiration, and the procedure was immediately stopped and this patient was referred for surgery.

The viability of the cysts was confirmed in all cases by the presence of viable scolices in the aspirated fluid. The ethanol injected ranged between 12 and 250 mL per session. The mean time for double percutaneous aspiration and ethanol injection procedure was 39.3 minutes lasted (range 35 - 55 minutes). In symptomatic patients, the loss of cyst tension caused immediate disappearance of abdominal mass, and jaundice disappeared within 4-17 days. The mean hospital stay was 2.9 days (range 2-

7 days).

The cysts disappeared in 9 (64.3%) of the remaining 14 patients of group I with reconstitution of liver parenchyma; while 3

(21.4%) patients showed a solid pattern, i.e., inactive cyst with heterogeneous hypoechoic or hyperechoic degenerative contents without daughter cysts. In the remaining 2 (14.3%) patients, there was a residual small liquid component with 80% decreased volume compared with the pretreatment size Figure(9). These cysts were treated by per- cutaneous aspiration, and no viable scolices were found in the aspirated fluid.

Local recurrence was observed in 2 patients (14.3%) after one year. One patient presented with fever, jaundice, and dilatation of the biliary tree on ultrasonography while the other patient was discovered during the routine follow up. Both patients were treated with re-aspiration and ethanol injection. No viable scolices were found on parasitological examination, and, ultrasonography showed the reconstitution of the  liver  parenchyma  after  6  months.

There was a clear relationship between the baseline volume of the cysts and the time taken to obtain the stable post treatment sonographic pattern; the smaller the cysts, the shorter the healing time. The difference between the time of healing (i.e., disappearance, solidification, or small liquid component sonographic appearance) of the cysts • 5 cm (range, 20-70 days; mean, 43 ± 14  days) compared with cysts > 5 cm (range, 3-24 months; mean, 12 ±

8 months) was statistically significant (P<0.05; odds ratio = 2.33; 95% CI, 1.71-3.351) Table(3).

Table (3) : Relation between size of the cyst and healing time.

S: Significant

Pyogenic liver abscesses due to Escherichia coli infection developed in 2 patients (14.3%)

15 and 60 days after double percutaneous aspiration and ethanol injection. In both cases, the abscesses were drained percutaneously and reconstitution of liver parenchyma was observed on sonographically 2 month later. Some other minor complications were recorded in 3 patients (21.4%) in the form of abdominal pain in 2 patients (14.3%) and mild subcutaneous infection at site of aspiration in

1 patient (7.1%).

In Group II :

Four patients (26.6%) underwent cholecystectomy for incidental gall bladder stones. Omentopexy was carried out in all patients. The mean operative time was 80 minutes ranged from 40 minutes to 180 minutes. The patients started regular diet on the second post-operative day. There was no major postoperative morbidity. Two patients (13.3%) were converted into open surgery due to extensive pericystic adhesions. One patient (6.7%) developed postoperative mild dyspnoea with minimal right side pleural effusion

confirmed by CT scan assessment which was treated conservatively. Two patient (13.3%) had minimal postoperative bile leak which gradually decreased within 2 weeks. One patient (6.7%) developed unexplained fever that resolved spontaneousely within 2 days. There was no intraperitoneal rupture of the cyst or peritoneal spillage. The mean hospital stay was 6.05 days (ranges 4-17). There have been no recurrences in the follow up. The cysts disappeared in all patients of  the group with reconstitution of liver parenchyma during the postoperative ultrasonographic follow up.

In both groups of the study, there were no mortalities, no anaphylaxis, and no other complications recorded as sub-hepatic collection, intractable bile leak, peritoneal spillage   or   major   wound   infection.

The difference between both groups of the study regarding time of the procedure, complications as bile leak, development of cavity infection or abscess, intracystic bleeding, disappearance of the cyst, local recurrence and mean hospital stay time are summarized in Table(4).

Table (4): The difference between both groups.

S: Significant     NS: Non-Significant

Discussion:

Hydatid disease is still frequent in endemic areas. The true incidence of this disease is difficult to estimate, as it is usually asymptomatic in most patients.15

Approximately 50%-70% percent of the cysts are localized in the liver. The right lobe is affected in 85% of patients, and in one quarter to one third of cases the cysts are multiple.16

The detection of cysts had increased with the advent and routine use of ultrasonography which in addition to the diagnosis, ultrasonography provides information about the cyst wall, fluid content and surrounding liver tissue. CT is carried out to further delineate the anatomy and rule out proximity of vital structures.16,17

Our study showed that double percutaneous aspiration, ethanol injection and re-aspiration (PAIR) is highly effective with very few side effects and no mortality rate. Regarding the disappearance of the cysts with reconstitution of liver parenchyma on ultrasonography, we reported a high percentage (64.3%) of cysts disappeared. This correlates with the series of Ustünsz and coworkers, where 70% of patients treated with PAIR showed disappearance of the cysts.18 On the other side, in the experience of Etlik and his colleagues, none of the cysts treated with PAIR disappeared.19

In our study, the PAIR technique showed a recurrence rate of 14.3% ; compared to 10.8% in a large series of 510 hydatid liver cysts in the 355 patients.20

Moreover, 64.3% of  our patients showed disappearance of the cyst after PAIR technique with reconstruction of liver parenchyma, 21.4% showed a solid pattern (inactive cyst), and

14.3% of patients had no disappearance of the cyst but showed a reduction of 50-80% of cystic baseline volume. These results correlates with those of Dziri and his associates in their study where disappearance of the cyst occurred in 71% while solid pattern was seen in about

17% of their study.21

In our study, the double percutaneous aspiration and ethanol injection procedure lasted between 35 and 55 minutes and the mean hospital stay was 2.9 days (range 2-7 days). This correlates with other studies that showed

a mean hospital stay of 2.4 days in non- complicated cases.22

In our experience, no mortalities have been recorded. In other series with larger number of cases and longer follow-up periods, the mortality range was from 0.3% to 2%.Their mean operative time was 75 minutes; and mean hospital stays ranged from 5.6 days in laparoscopic series to 10 days in open radical surgery compared to our study with 80 minutes mean operative time and nearly 6.05 days mean hospital stay.23

The major advantages of laparoscopic surgery also include decreased pain, earlier mobilization, shorter convalescence and high acceptability by patients. Laparoscopy also offers the advantage of allowing inspection of the inner surface of the cyst wall for signs of malignancy and biopsies of suspicious lesions.23

Saglam proposed the laparoscopic technique as a method for treating hydatid liver cyst.24

In 1996, Bickel et al reported 10 cases of hydatid liver cyst treated laparoscopically without mortality or relapse.25 In 1995, Alper reported 16 cases of hydatid liver cyst solved by laparoscopy with 2 postoperative abscesses and no relapse. Among these, 4 cases were converted because of adhesions or difficult localization.26

In our study, no relapse after the laparoscopic cure of the hydatid liver cyst had been observed. Hydatid relapse has been reported only in one study of Yorganci and his colleagues and was treated again by laparoscopy. These procedures should be considered with care because of allergic and anaphylactic risk and because of the risk of hydatid spreading.27

Usually, postoperative care is easy, with an average hospitalization of 8-10 days in the published trials.26,27 In our study, the average postoperative hospitalization was 6.05 days (ranges 4-17).

According to literature, complications of laparoscopic management of hepatic cysts have ranged from 0 to 15% and include dyspnea, pleural effusion, ascites, hemorrhage, infection and subhepatic bile collection.28 However, we did not have any major morbidity in our patients apart from prolonged abdominal tube drainage

in two patients and minimal right sided pleural effusion in another one patient.

In our study we used Mebendazole pre and post-operatively. According to literature, the new scolicidal agents, if administrated before can prevent recurrences. Mebendazole or albendazole reduce as much as possible the risk of the spreading of the hydatid cyst.25,26

We consider that, if the hydatid cyst is fit for a minimally invasive surgical approach, drug treatment should be given before the surgical intervention.

In Alperís trial, the medical treatment was given 10 days before surgery and continued for 3 months after surgery with no relapse reported.26 In our trial, medical treament was administrated for 10 days preoperatively and continued for 8 weeks posoperatively and we had   no   long-term   hydatid   recurrence.

In conclusion, in spite of reservations and doubts, the results obtained until now show that hepatic hydatid disease may be treated by a minimally  invasive approach. Our results confirm that double percutaneous aspiration and ethanol injection is an effective and safe technique for previously untreated patients with viable univesicular hydatid liver cysts not only in the short term, but also in the middle term. Double percutaneous aspiration and ethanol injection has a low cost, the hospital stay is very short, and the few cases of local recurrence can be retreated. Therefore, although surgical excision is considered the treatment of choice for hydatid liver cysts, double percutaneous aspiration and ethanol injection procedure can be considered as first-line treatment in patients with viable univesicular hydatid liver cysts.

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