Current Concepts in Curative Surgery for Cystic Echinococcosis of Liver

Abstract

Cystic echinococcosis (CE) may cause unspecific symptoms like abdominal discomfort in the right upper quadrant of the abdomen due to capsule tension pain of the liver related to an increased expansion of the cyst. Further, a growing cyst may put pressure on intrahepatic bile ducts or can get direct access to the biliary system with complications like obstruction, cholangitis and fistulas. Large or rapid growing cysts may cause compression of blood vessels with thrombosis or Budd-Chiari syndrome. However, the vast majority of patients with CE of the liver is asymptomatic. CE of the liver can be cured surgically in many cases. In the past, cystectomy with resection of the pericyst components was performed as a standard. The today’s parenchymal sparing state-of-the-art surgery is endocystectomy combined with partial cystectomy. This procedure includes (i) evacuation of paracyte-derived cyst content, (ii) sterilization of the cyst wall (host) and (iii) deroofing of the cyst (partial cystectomy). Here the advantages, risks and outcomes of the surgical approaches are discussed, and the need for an interdisciplinary treatment of these patients is outlined.

1. Introduction

Echinococcosis in humans is mainly caused by Echinococcus granulosus (E. granulosus) or Echinococcus multilocularis (E. multilocularis), which cause cystic echinococcosis (CE) or alveolar echinococcosis (AE), respectively [1]. It is an important parasitic disease of humans, which represents a considerable endemic health problem in some areas of the world. CE affects the liver in up to 70%, less frequently the lung, the spleen, the kidney, the bones and the brain can be involved [2, 3, 4]. CE of the liver is asymptomatic in most cases; however, both biliary and vascular complications like cholestasis, cholangitis, biliary fistula and thrombosis or Budd-Chiari syndrome, respectively, are observed. In some cases, CE can become even a life-threatening disease. E. granulosus is endemic in South America, Eastern Europe, the Middle East and China with incidence rates of up to 50 per 100.000 persons per year [5, 6]. A prevalence of up to 95% was described in some slaughter houses in South America [7]. On the other hand, there are zones without hydatid cysts like Tanzania, Cyprus, Malta or New Zealand [8], which can be attributed to the health policy of these countries. Although the mortality rate of CE is low with 2.2%, morbidity is high [9].

An acute course of the infection has never been described in humans [10], and the development of a cavity and of the germinal and laminated layer of the cyst wall occurs 10–14 days after the infection at earliest [11]. The growth of the cysts is only partially understood, and the growth rate is variable [12]. The behaviour of cysts in different stages is often unpredictable and varies greatly [13, 14].

Diagnosis of CE is often coincidentally in patients presenting with unspecific abdominal symptoms, pain or poor appetite [15]. Imaging techniques like ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are essential for diagnosis and clinical management [16, 17, 18].

Treatment options have been discussed by the “Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans” and are published by the WHO-Informal Working Group on Echinococcosis [19]. In contrast to the watch and wait strategy, therapeutic options include conservative treatment with benzimidazoles, interventional sterilization techniques and surgical approaches. While surgery can provide curative treatment in selected patients, the overall treatment strategy depends on various disease dependent factors (size, number and location of cysts), individual contraindications for surgery, intolerance to benzimidazoles and on CE-derived complications.

2. The hydatid cyst structure and its progress

In order to understand the different surgical approaches, the structure and progress of a cyst in the liver should be known. The cyst in the liver consists of three layers. Outside there is the adventitia or pericyst. It consists of compressed liver parenchyma and fibrotic tissue and results from the expanding parasitic cyst. Further inside is a laminated membrane or ectocyst, which is easy to separate from the pericyst. The innermost layer is called germinal epithelium or endocyst. It is a single layer of cells, and it is the only living component. The cyst is filled with hydatid fluid, solices and sometimes brood cysts or daughter cysts [20].

The history of a hydatid cyst in the liver consists of two phases. First the cyst growths and could rupture due to a high pressure inside. This might lead to complications like acute allergic reaction, infection or jaundice. During the second phase of the hydatid cyst, it is full of solices and daughter cysts, which replace the hydatid fluid. In this phase, calcifications occur in the pericyst. The growth of the cysts may cause pressure on the surrounding tissue with symptoms like upper abdominal pain, discomfort or obstructive jaundice [21].

3. Complications of CE of the liver

In about 40% of hepatic CE complications occur. The most common complication is infection, which can be asymptomatic or clinically noticeable with pain and fever. Another common event is the intrabiliary rupture of the hydatid cyst, which can happen in two ways: the occult rupture is marked by the drainage of cystic fluid into the biliary tree. Its incidence is up to 37%. The frank rupture is characterized by an overt passage of intracystic material to the biliary tract. It occurs in 3–17% of the patients. The incidence of intrabiliary rupture into the right hepatic duct is indicated with 55–60%, into the left hepatic duct with 8–11% and into the gallbladder with 5–6%. The intrabiliary rupture causes further biliary complications like cholangitis or hydatid biliary lithiasis [22, 23, 24]. In a few cases, rupture into the thorax or into the peritoneum is possible. Intrathoracic rupture can cause lesions of the pleura, the lungs and bronchi, which can lead to coughs and dyspnea [25]. The rupture into the peritoneal cavity is rare and occurs spontaneously in most cases. It leads to abdominal pain, allergic reactions, vomiting and nausea [26]. Very rare complications of hepatic CE are fistulization to the skin, portal hypertension or vascular erosions [27].

4. Diagnosis

4.1 Clinical symptoms

After the infection, patients are mostly asymptomatic. Symptoms depend on the size and number of the arisen cysts and on the effect within the affected organ. Especially non-complicated cysts are often asymptomatically and diagnosed incidentally. Vague symptoms comprise abdominal pain in the right upper quadrant or epigastric pain due to an enlarged liver. Symptoms of complicated cysts range from anaphylaxis and infections to jaundice due to biliary complications [28].

The diagnosis of hepatic CE requires both imaging and serologic and immunologic investigations. Routine laboratory values might show eosinophilia in some cases. Serum alkaline phosphatase levels are elevated in about 30% of patients.

4.2 Serology and immunological tests

Serological tests are used to detect antibodies against the parasite. Immunglobuline (Ig) G antibodies are elevated after exposure to the parasite, and in cases of active infection, specific IgM and IgG antibodies are high. Circulating hydatid antigen can be detected in the serum with ELISA-tests and can be used for monitoring after therapy. The sensitivity of ELISA-tests is up to 90% and therefore preferred. In patients with hepatic CE, the indirect immunofluorescence assay (IFA) is the most sensitive test (95% sensitivity) [29].

4.3 Imaging techniques

The screening method of choice is ultrasonography (US). CT scan provides information concerning lesion size, location and relations to intrahepatic structures and therefore plays an important role in preoperative diagnostics to evaluate vascular, biliary or extrahepatic extension of the cyst.

4.3.1 Ultrasonography

It is the primary radiological technique with an accuracy of 90%. Solitary or multiple cysts, daughter cysts, separation of membranes, but also complications can be diagnosed. Doppler US provides information on the interference with vascular structures. US features are classified by Gharbi et al. [30] as follows: type I shows a pure fluid collection, in type II there is a split wall additionally. Type III presents septa and/or daughter cysts. Type IV cysts show a heterogeneous echo pattern, and type V cysts are calcified. Another classification was introduced by the World Health Organization (WHO) [31]: they range from CL (single cyst), CE 1 to CE 5. The type depends on the disease status and morphological type of the cyst.

4.3.2 CT scan

The highest sensitivity for detecting hydatid cysts with number, size and location is given by a multi-detector row CT scan. Additionally, intrabiliary ruptures or the presence of other complications can be diagnosed. CT scan is important for the planning of surgical intervention.

MRI adds little information and is therefore rarely indicated. In cases of intrabiliary rupture, endoscopic retrograde cholangiopancreatography (ERCP) is an important tool for diagnosis or intervention [32].

5. Surgical treatment

Surgery is the gold standard treatment for hepatic CE and aims to remove the CE. Cure can be achieved with various surgical approaches including pericystectomy, liver resection and parenchymal sparing endocystectomy with partial cystectomy. The choice depends on the number and size of cysts as well as on the condition of the patient. One important point and challenge is avoiding the spillage of cyst content and thus to decrease the risk of recurrence [33]. In the following the standard surgical procedures for CE of the liver are described, and advantages and disadvantages of such are summarized (Table 1).

Surgical technique	Advantages	Disadvantages	Potential complications	Outcome
Parenchymal sparing approach	Excellent view Good control of the parasite-derived material Less complications Less recurrence	Open approach	Biliary lesions	Low risk for complications Recurrence-free up to 48 months
Pericystectomy without liver resection	Less invasive than liver resection	Risk for sclerosing cholangitis	Biliary fistula Cavity infection	Complication rate up to 24% Recurrence rate up to 25%
Pericystectomy with liver resection	Radical removal of the cyst and all components Opening of the cyst can be avoided No risk for cavity infection and lower risk for biliary fistula	More complex and difficult procedure compared to the conservative approach	Bile leakage Postoperativ bleeding Liver failure Wound infection Incisional hernia	Complication rate 3–30% Recurrence rate up to 4%
Laparoscopic approach	Less hospital stay Less pain Less wound healing complications	Posterior and superior segments of the liver are difficult to reach Difficulties with aspiration of the cyst content Risk for spreading of the cyst content	Bile leakage Cavity infection Port-side infection and/or contamination with CE	Complication rate up to 15% Recurrence rate up to 11%

Table 1.

Advantages, disadvantages and outcome of different surgical procedures.

5.1 Endocystectomy with partial cystectomy

Endocystectomy with partial cystectomy is a novel parenchymal sparing surgical technique for CE of the liver [34]. After laparotomy, the liver is dissected free from its ligaments. Intraoperative ultrasound verifies the location of CE. Subsequently, a layer of cloths soaked with normal saline solution is placed in the abdomen to protect tissue surrounding the liver. These cloths are covered by a second layer of cloths that are soaked with 20% saline solution (Figure 1). This hyperosmolar saline prevents a spread of CE even in the case of contamination with hydatid fluid.

Figure 1.

Layer of cloths soaked with normal saline solution and a second layer of cloths soaked with 20% saline solution is placed in the abdomen to protect the tissue surrounding the liver.

A 12 mm safety trocar is inserted into the cyst (Figure 2), and the parasite-derived cyst content is sucked out completely (Figure 3). After removal of the trocar, a white test is performed [35] to exclude access from the cyst to the biliary system. Bile fistulas are closed with stitches, and the cyst is filled with hyperosmolar saline for 15 minutes to devitalize remnant protoscoleces (Figure 4). Finally, the cyst is deroofed (Figure 5) and filled with omentum (Figure 6a and b).

Figure 2.

Noncutting twelve-millimeter trocar is inserted into the cyst.

Figure 3.

Parasite-derived cyst content is sucked out completely via the trocar.

Figure 4.

Hyperosmolar saline fills the cyst for 15 minutes.

Figure 5.

Deroofed cyst.

Figure 6.

a. Omentum for omentoplasty. b. Cyst filled with omentum.

A great advantage of this procedure is the excellent view and control of the parasite-derived material during surgery. Complications, i.e. bleeding, postoperative bilioma or fluid collection, have not been reported. Most importantly, endocystectomy with partial cystectomy as described here prevents from recurrence of CE [34].

The following surgical procedures for treatment of CE are described considering their disadvantages:

5.2 Pericystectomy

Pericystectomy of the CE includes total cystectomy with removal of the parasite-derived cyst components together with the entire pericyst. It can be performed with the resection of the surrounding liver tissue or without liver resection to preserve healthy liver parenchyma. Pericystectomy combined with liver resection can be indicated for large or multiple or complicated cysts, if the future liver remnant is large enough for excellent hepatic function.

Disadvantages of pericystectomy without liver resection are the risk for sclerosing cholangitis, biliary fistula and cavity infection. There is a complication rate of up to 24% and a recurrence rate of up to 25% [36]. Pericystectomy with liver resection is a radical removal of the cyst, all components and surrounding liver tissue. The procedure is more complex and difficult compared to less invasive approaches. Disadvantages are the risk for bile leakages, postoperative bleeding, liver failure, wound infection or incisional hernia. There are higher complication rates with 3–30% depending on the extent of resection. The recurrence rate is reported in up to 4% of cases [37, 38].

5.3 Laparoscopic approach

The laparoscopic approach for surgical treatment of liver CE has been considered as treatment option [39]; however, it is a challenge to reach cysts located in the posterior and superior segments of the liver. Furthermore, there are some exclusion criteria for a laparoscopic approach like intrabiliary rupture, central localization of the cyst, size of the cyst of more than 15 cm, multiple cysts or calcified walls. Further, it is almost impossible to avoid spilling cyst content during the evacuation process. Thus, recurrence of CE is described in 11% of cases [40, 41]. Another disadvantage of the spillage is the higher risk for allergic reactions.

5.4 Interdisciplinary treatment

Interdisciplinary treatment of these patients is recommended. For the diagnosis the cooperation with experienced radiologists is important. Surgery should be performed in a specialized centre for hepatobiliary surgery. Perioperative Albendazole is recommended to prevent recurrence. A dose of 10 mg/kg/day shall be given for 6 months after surgery. Since regular blood tests are indicated, there should be an interdisciplinary treatment of these patients. Side effects of Albendazole therapy are mild abdominal pain, nausea, vomiting, pruritis or headaches. Leucopenia, eosinophilia, icterus or mild elevation in transaminase levels can occur.

6. Discussion

The high variability of hepatic CE requires individual treatment depending on factors like cyst characteristics, but also on available resources and the preference of the treating physician. Due to a lack of randomized clinical trials, there is a low level of evidence especially in comparing different therapy modalities with each other. However, surgery has been considered the best option, even after implementation of medical treatment or percutaneous procedures.

7. Conclusion

Hydatid disease is a public health problem in some areas of the world. The liver is affected mostly with up to 75% of patients. However, CE can be cured with surgery combined with medical treatment with Albendazole. There is no recurrence of CE reported after novel parenchymal sparing endocystectomy with partial cystectomy which is associated with very low postoperative morbidity [34]. However, there is still a controversial discussed on the best surgical treatment for hepatic CE.

Acknowledgments

No funding was obtained.

Conflict of interest

The authors declare no conflict of interest.