WHO-IWGE ultrasound classification.
Hepatic hydatid disease has been reported from ancient times. It is a zoonotic infection caused by nine recognized species of tapeworms of the genus Echinococcus. Some of them are known to cause human echinococcosis, and there is reasonable doubt regarding the others. Diagnosis is supported by epidemiological history, clinical presentation, radiological imaging, and serological tests. Various pathological forms may become life-threatening, and in those cases, the treatment is extremely complex. The main objective of the treatment is to completely cure the illness in order to avoid further complications and recurrences. Hepatic surgery, using different techniques, achieves best results with acceptable morbidity and mortality rates. In the South of Chile, the geographical location in which we work, this illness is endemic with high incidence and prevalence. The hepatobiliopancreatic units of the regional surgical centers of Temuco have plenty of experience treating liver hydatid disease. In this chapter we shall focus especially on epidemiology, etiopathogenesis, diagnosis, and surgical treatment of hepatic hydatidosis.
- hepatic hydatidosis
- surgical treatment
Human echinococcosis, also called hydatidosis, is a zoonosis which has been known from ancient times. There are mentions about hydatid disease both in humans and animals in documents as old as the Ebers Papyrus and the Babylonian Talmud [1, 2]. Around the mid-nineteenth century, a significant breakthrough happened when the etiology and the life cycles of different
Cystic echinococcosis, the most common form of hydatidosis, is an endemic zoonosis caused by the larval stage (metacestodes) of the tapeworm
The most common form of hydatidosis is cystic echinococcosis caused by
Hydatidosis is caused by the larval stages of taeniid cestodes of the genus
The anatomical structure of the cyst has an outer acellular laminated membrane that allows the entry of nutrients from the host. Then there is the inner nucleated germinal membrane, in which the daughter vesicles are produced. In an asexual form, the protoscoleces are formed inside the daughter vesicles. The immunological system of the intermediate host reacts to isolate the parasite, forming a fibrous layer called adventitia, which can calcify with the passage of time (Figure 1A, B). The life cycle closes when the animal’s definitive host is fed by contaminated viscera, and each protoscolece can develop an adult tapeworm in its small intestine  capsules and scolices.
Currently, the diagnosis must always consider the epidemiological background. The definitive diagnosis is reached through the use of imaging and in some cases with the additional contribution of serology. In the near future, earlier stages of the parasitosis will be diagnosed by means of advances in immunological tests [24, 25].
4.1 Clinical features
Humans remain asymptomatic for a prolonged period of time after being infected due to the slow growth of the hydatid cyst in the liver (1–5 mm per year). Small and medium cysts of central hepatic location are usually asymptomatic, or a slight pain in the epigastrium and right hypochondrium might be reported by the patient, together with a sensation of abdominal discomfort. Besides, the previous immune status of the patient and the anatomical location of the cyst could determine a late manifestation of the first symptoms . When the cysts grow and reach a significant size, the mass effect on the bile tree and hepatic vasculature determine other clinical manifestations derived from biliary obstruction, portal hypertension, and Budd-Chiari syndrome. The magnitude of this effect will determine different degrees of jaundice and portal hypertension, which may range from a slight increase of bilirubinemia and the appearance of venous collaterals of the abdominal wall to very severe jaundice, ascites, and upper digestive hemorrhage secondary to rupture of the gastroesophageal varices .
In 1981, Gharbi reported an ultrasonography classification of the hepatic hydatidosis, describing five categories in relation to the morphological findings of the cysts, according to their stage of evolution . In 2002, based on this classification, the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) formulated a new classification adding two more categories, with the aim of guiding in the selection of the best treatment and follow-up of the results obtained (Tables 1 and 2) [29, 30, 31]. Current imaging offers several tools to guide a better management of this disease. Usually, the imaging diagnostic begins with the use of ultrasonography (US), and then other imaging tests could also be used to achieve a better diagnosis of the most complex forms of parasitosis, such as contrast-enhanced ultrasound (CEUS), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiography (MRC), endoscopic retrograde cholangiography (ERC), and conventional X-rays.
|WHO-IWGE||Radiologic characteristics||Definition of cyst|
|CL||Unilocular cystic lesion with uniform anechoic content, cyst wall not visible||Cystic lesion|
|CE1||Unilocular cystic lesion with uniform anechoic content, cyst wall visible, snowflake sign||Active cyst|
|CE2||Multivesicular, multiseptated cysts, daughter cysts present, honeycomb sign||Active cyst|
|CE3A||Unilocular cyst containing liquid with a floating membrane inside, water-lily sign||Transitional cyst|
|CE3B||Cysts with daughter cysts in solid matrix|
|CE4||Cysts with heterogeneous hypoechoic or hyperechoic degenerative contents, no daughter cysts||Inactive cyst|
|CE5||Cysts characterized by a thick calcified wall, which is arch shaped, producing a cone-shaped shadow; degree of calcification varies from partial to complete||Inactive cyst|
|WHO||Surgery||PAIR||Drug therapy||Suggestion||Resource setting|
|CE1||✓||✓||<5 cm ABZ PAIR
>5 cm PAIR+ALB
|CE2||✓||✓||✓||Other PT + ALB
|CE3a||✓||✓||Other PT < 5 cm
ABZ PAIR >5cmPAIR+
|CE3b||✓||✓||✓||Non-PAIR PT + ABZ
|CE4||Watch and wait||Optimal|
|CE5||Watch and wait||Optimal|
The US is widely used due to its low cost and high-definition images, which allow to define the pathological characteristics of hepatic hydatid cysts and other locations in the peritoneal cavity (Figures 2–4). It is also useful for the differential diagnosis of hydatid cyst with other liver tumors. The use of mobile devices allows having a portable tool for the screening of populations in endemic areas with high risk of affectation [30, 32, 33]. Due to the difficult differentiation of certain forms of alveolar echinococcosis from other kinds of hepatic tumors, CEUS is being increasingly used in certain regions with endemic affectation of this pathology .
4.2.2 Computed tomography
Sometimes, the ultrasound does not help much in the diagnosis of liver hydatidosis for different reasons, such as obesity, presence of abundant intestinal gas, hydatid recurrence, or residual cavities secondary to previous surgery. When that is the case, CT is used, taking advantage of its higher sensitivity and specificity. Unenhanced CT allows to have a better radiological diagnosis of the different forms of cyst calcification . The contrast-enhanced CT aids in choosing the best surgical techniques according to the different forms of presentation or complications related to the disease, e.g., by allowing a more accurate appreciation of the involvement of the vasculature and biliary tree. CT also aids in diagnosing the cystic migration to the thorax and the biliary tree [35, 36]. Another advantage of the use of contrast-enhanced CT is to achieve a better differential diagnosis from other focal liver lesions  (Figures 5
4.2.3 Magnetic resonance imaging
MRI is useful for diagnosis of cases of cholangiohydatidosis. Compared to US and CT, the MRI T2-weighted sequence is better at defining the internal structure of the cyst. In general, it is indicated for patients that present difficulties when performing ultrasound, such as bowel gas excess, previous surgeries, disseminated hydatidosis, and obesity. In addition, MRI is recommended when CT is contraindicated due to comorbidities. MRC is used to determine the existence of cysto-biliary fistula and the presence of hydatid material in the biliary tree. It also visualizes the cysto-biliary fistula both toward the bronchi and to the biliary tree [38, 39] (Figures 11a, b–17).
4.2.4 Endoscopic retrograde cholangiography
The rupture of a hydatid cyst in the intrahepatic bile duct can initiate some complications, which might become serious mainly due to the development of cholangitis and septicemia. In these cases, the ERC provides the diagnosis and performs the removal of hydatid material, with the objective of improving the general conditions of the patient before carrying out the definitive surgical treatment .
Currently, diagnosis and follow-up of patients with cystic echinococcosis are achieved especially through imaging. Serology is used for the same purpose, using the detection of IgG-specific antigens. However, low sensitivity and specificity rates have been reported. In addition, false positives appear during follow-up due to the persistence of antibodies over time. There is a lot of research (recombined proteins, isotopic antibodies, subisotopic IgG, synthetic peptides), which seek to develop new antibodies by means of the molecular technique, allowing a better diagnosis of this parasitosis [41, 42].
Frequently, there are complications secondary to the hepatic location of the cyst or by involvement of adjacent organs, in which case symptoms and signs of greater intensity will appear. Among them, the following should be mentioned:
More intense pain might appear when the Glisson capsule is stressed by larger cysts. In these cases, an abdominal mass mobilizing together with the respiratory movements is visualized during the physical examination. These giant cysts are easily visualized with the ultrasound. CT allows to define in more detail the elevated right hemidiaphragm and the development of secondary pulmonary basal atelectasis.
Another complication of large cysts occurs when there is an intrahepatic breach or rupture of the cyst to the peritoneum either spontaneously or by trauma. The discharge of fertile hydatid fluid in the liver or peritoneal cavity causes anaphylaxis of a different magnitude and new hydatid implants . These complications are better visualized with the use of CT.
Cyst rupture and emptying of hydatid fluid or membranes into the biliary tree lead to obstructive jaundice, many times accompanied by severe acute cholangitis [44, 45]. The cysts can become infected as well and determine the formation of liver abscesses, which can sometimes lead to septicemia. In these cases, CT and MRC allow to achieve a better definition of the characteristics of the abscess and whether there is emptying of hydatid material into the biliary tree.
The chronic inflammatory process of hepatic cysts located in segments of the liver dome determines firm adhesions to the right hemidiaphragm and even transits toward the pleuropulmonary space. As a result of this transphrenic transit, patients may present pleural empyemas or bronchopneumonia . CT and MRC help to achieve a better definition and provide the most appropriate and safe management.
There are occasions in which large cysts may be more complicated due to the simultaneous rupture and emptying of hydatid material to the biliary tree and bronchi. A bilio-pleuro-bronchial fistula is established with the occurrence of the pathognomonic sign of bilioptysis, i.e., the expectoration of the bile. These patients present a fairly severe septic episode with hepatic and respiratory functional compromise . The thorax-abdominal CT and MRC are useful to diagnose this complication .
Rarely, cysts located adjacent to the retrohepatic vena cava can rupture and cause severe cardiorespiratory failure due to bilateral pulmonary arterial embolism with multiple pulmonar hydatid dissemination . In that case, a CT angiography (CTA) is used to better diagnose this serious complication.
6. Surgical treatment
The main objective of the treatment of hepatic hydatidosis is the eradication of the parasite and avoidance of recurrence. There is consensus, in considering surgery as the best option to achieve this purpose. It is currently possible to perform different surgical techniques with acceptable rates of morbidity and mortality, which are applied according to the pathological conditions of cysts. In cases of greater complexity, surgery can be complemented with other therapies such as minimally invasive procedures and chemotherapy. Surgical treatment has indications and contraindications depending on the patient’s condition and the forms of disease presentation .
At the dawn of the surgery to treat hepatic hydatidosis, only conservative techniques were used. Among them, marsupialization consisted in the opening and extraction of the parasite followed by externalizing the residual cavity toward the abdominal wall, waiting for the closure by secondary intention. Cysto-enteroanastomosis was also performed, anastomosing the hepatic residual cavity into the duodenum or a defunctionalized jejunal loop. Currently, these conservative techniques are not indicated due to the high risk of complications such as recurrences, liver abscesses, intestinal obstruction, biliary fistulas, biliomas, biliary peritonitis, cholangitis, and septicemia. However, there are surgical centers that report good results in cases with large cysts treated by laparoscopic cystojejunostomy .
There are various procedures of resective surgery performed in different surgical centers. When indicated, it is necessary to consider age, general condition of the patient, pathological state of the cysts and location in other organs, and the existence of important comorbidities difficult to control. Despite being a benign pathology, its evolution can sometimes be very complicated, requiring multiple surgeries and leading to a poor prognosis. The surgical resections are performed either through open or laparoscopic surgery. The following are the most used techniques from least to greatest complexity.
6.1 Subtotal cystectomy by open surgery
Right or bilateral subcostal laparotomy.
In order to obtain a good access to the cyst, the section of the round ligament and the dissection of adhesions to the diaphragm or adjacent organs might be required. The use of intraoperative ultrasound is useful in posterior and central cyst locations, to avoid injuring the retrohepatic cava vein or hepatic veins.
During puncture and removal of the fluid and hydatid membrane, it is necessary to isolate the surgical field with compresses embedded in scolicidal agents (20% hypertonic saline solution or diluted povidone iodine).
Wide resection of the adventitia and further revision to eliminate daughter vesicles in cavities located in the remaining adventitia.
Identification and suture of biliary communications.
Closure of the residual cavity by means of capitonnage or omentoplasty. In giant cysts, capitonnage is not recommended to avoid distortion of the biliary tree and intrahepatic vasculature with subsequent functional sequelae.
In some cases, to prevent postoperative biliary fistulae, a drain is placed in the residual cavity, or a choledocostomy with a Kehr tube is performed.
When the cyst is close to the main bile duct or to the subhepatic and cava vein, the adjacent adventitia should be left in situ to prevent biliary fistulae or bleedings.
6.2 Laparoscopic subtotal cystectomy
Laparoscopic subtotal hepatic cystectomy has all the advantages of minimally invasive procedures (Figures 22–24). It offers magnified vision with better appreciation of the cyst, residual cavity, and biliary communications. In addition, it presents less postoperative pain and earlier discharge. Comparative studies are reported between the two techniques, and the future trend seems to prefer laparoscopic technique . However, technical difficulties currently persist to avoid the spillage of fertile hydatid material into the peritoneal cavity with anaphylactic reactions and secondary hydatid implants. For this reason, and to prevent this complication and a possible uncontrollable bleeding, the laparoscopic approach is contraindicated in the following situations:
Cyst diameter more than 10 cm
More than three cysts and/or presence of peritoneal cysts or in other organs
Very thin or calcified adventitia
Cysts located in the dome and central locations of the liver
Complicated cysts with rupture and emptying on the biliary tree or peritoneum
Imaging signs of accentuated pericystic inflammation
Cysts with fibrous adhesions to the diaphragm on the way to a thoracic migration
Following the rules of laparoscopic liver surgery, the location of the entrance ports depends on the anatomical location of the cysts. To prevent the spillage of hydatid material into the peritoneal cavity, it is necessary to have a good puncture and aspiration system, similar to Perforator-Grinder .
Open or laparoscopic pericystectomy is based on the concept of complete parasite removal. This technique consists of resecting the cyst by a plane through the hepatic parenchyma adjacent to the adventitia, thus achieving avoidance of recurrence due to the presence of daughter vesicles in the adventitia or in the surrounding hepatic parenchyma . In cases of complicated cysts, pericystectomy is not recommended due to the risk of further bleeding or bile duct injuries. Previous radiological studies are crucial to determine the relationship of these structures with the cysts. Currently, laparoscopic pericystectomy helps to prevent the aforementioned risks thanks to its magnified vision, more efficient hepatic transection instruments, and widespread access (Figure 25). Well-trained surgeons in laparoscopic hepatic surgery have a better chance of successfully performing this technique .
6.4 Hepatic resection
Sometimes it is necessary to carry out liver resections, e.g., when there are hydatid recurrences in the same lobe previously operated or in residual cavities, which have the risk of subsequent infection with development of liver abscesses and cholangitis. When the infection is controlled by antibiotic therapy or percutaneous drainages, it is recommended to resect the compromised lobe, which is usually more atrophic. This surgery will be consequently more laborious. Nevertheless, the compensatory hypertrophy of the unaffected lobe determines a lower risk of postoperative hepatic failure. With the aim of completely eradicating the parasite and preventing recurrence, several surgical centers perform hepatic resection more frequently by both open and laparoscopic surgeries with acceptable morbidity and very low mortality. Liver resection is more indicated in alveolar echinococcosis by higher frequency of recurrence and infiltrative behavior similar to malignant neoplasms. There are recent reports of liver transplantation and also ex vivo resection surgery with autotransplantation for this type of echinococcosis . Summarizing, hepatic resection, not very used in the past, now appears as a viable alternative for selected cases carried out in specialized reference centers.
The morbidity of resective surgery depends on the complexity of the hydatidosis and the magnitude of the surgery performed. Among the most difficult to treat are biliary fistulas, bleeding, and infections. For example, for patients with fistulization of the cyst toward the bile duct and thorax, it is advisable to work in stages, e.g., treating cholangitis first, and then, when the patient is stabilized, a pleural empyema is drained. Once general conditions have been recovered, the resective surgery is indicated. In relation to morbidity and mortality rates, what has been reported so far shows a great disparity of figures. A surgeon from our university conducted a study of the risk factors that determine the postoperative morbidity in a significant number of international publications. The results indicate a fairly low level of evidence . The challenge is to perform a prospective series, to achieve consensus on the indications of surgery to treat this complex disease.
7. Percutaneous treatment
This therapy is carried out by means of puncture, aspiration, injection of scolicidal agents, and reaspiration of fluid and hydatid membranes (PAIR). The procedure is performed under ultrasonographic guidance in selected cases. This procedure was developed by a Tunisian team in 1986. The WHO recommends this procedure because it is less invasive when compared to surgery, allows a good evacuation of the parasite, reduces the time of hospitalization, and is less expensive. The following guidelines contain indications and contraindications for this procedure (Tables 3 and 4) . It is necessary to have anesthesiological support to treat an eventual anaphylaxis crisis due to hydatid fluid spillage while PAIR is performed .
|1. Non-echoic lesion 5 cm in diameter|
|2. Cysts with daughter cysts and/or membrane detachment|
|3. Multiple cysts if accessible to puncture|
|4. Infected cysts|
|5. Patients who fail to respond to chemotherapy alone|
|6. Patients in whom surgery is contraindicated|
|7. Patient who refuse surgery|
|8. Patients who relapse after surgery|
|9. Children >3 years old|
|10. Pregnant women|
|1. Noncooperative patient|
|2. Inaccessible or risky location of the liver cyst|
|3. Cyst in the spine, brain, and/or heart|
|4. Inactive or calcified lesion|
|5. Cyst communicating with the biliary tree|
The use of treatments with drugs capable of penetrating and collapsing hepatic hydatid cysts is reported in numerous publications. These drugs are prescribed alone or together with surgery and less-invasive therapies such as PAIR. Currently, albendazole has shown effectiveness in reducing the size or even causing the death of the parasite. For this reason, it is employed to prevent recurrence after surgery. It is also used as the only therapy in patients who refuse surgery or who are inoperable due to disseminated hydatidosis or because of other comorbidities . In Chile, it is indicated preoperatively in doses of 10 mg/kg of weight for one cycle of 14 or 21 days and postoperatively from one to three cycles according to eventual appearance of hepatic dysfunction.
Hepatic hydatidosis is still a disease that spreads without epidemiological control in many parts of the world. Also, a continuous biological adaptation of the parasite to subsist in the intermediate host has been demonstrated, which would explain the great difficulties in eradicating this zoonosis. The permanent and even increasing incidence of this disease determines very high health costs necessary to treat patients, sometimes with complex pathological presentations. Efforts are being made to find new alternatives to diagnose early stages of the parasitosis. The creation of new vaccines with the intention of immunizing the intermediate host would determine a better control of human hydatidosis. Surgical advances are allowing for more and more radical surgical procedures with acceptable rates of morbidity and mortality. However, the implementation of minimally invasive surgeries presents significantly higher costs. Logic would dictate that the best path is to minimize the number of new patients affected through successful epidemiological control.
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