Hydatid disease of the urinary tract: an update

Introduction
Echinococcosis constitutes a parasitic infection caused by several species of the cestode Echinococcus. Human hydatid disease is generally caused by Echinococcus granulosus larvae. Echinococcus granulosus has a worldwide distribution and endemic regions exist in every continent. In Europe, the parasite is prevalent in the animal population (mainly sheep and cattle) of Greece and Mediterranean countries. Humans are immediate hosts that become infected following ingestion of food contaminated by the feces of dogs which are the definite hosts (1, 2). A primary hydatid cyst occurs when an organ traps the larvae following intestinal absorption. Arrest occurs in the capillary beds of the liver or lung in nearly 90 per cent of the cases (2-4). Hydatid cysts in organs other than the liver or the lungs are usually part of generalized echinococcosis, and only rarely are they primary cysts (5-9).
Echinococcosis of the urinary tract is a rare condition, and the kidney is the most frequently affected organ (10, 11). Renal involvement develops in approximately 2% to 4% of cases (12, 13). Echinococcus larvae may reach the kidneys through the blood stream, lymphatic system, or direct inoculation (14). Involvement of the prostate, the seminal vesicles, the adrenal, the retroperitoneum, and the retrovesical space has also been reported in sporadic cases. Hydatid embryos may reach to the pelvis either via arterial route after having passed the filter of liver and lung; or through lymphatic drainage of the gastrointestinal tract (15).

Location and clinical presentation
Renal hydatid disease usually occurs during primary infection by means of hematogenous spread, while infestation of other parts of the genitourinary tract results from direct extension of hydatid disease in an adjacent organ (16). The disease usually affects patients between the third and fifth decades of life who live in endemic areas. There are no specific symptoms and signs, and hydatid disease may remain silent for years. Symptoms develop when the cyst exerts pressure on tissue or present complications. Echinococcal cysts of the kidney are usually single and located in the cortex. They may reach 10 cm in size before causing symptoms (17, 18). Symptoms vary according to the stage of the disease and are seldom sufficiently characteristic to facilitate diagnosis. If renal hydatid disease is closed, in other words not communicating with the pelvis, there may be no symptoms until a mass is discovered. Patients may report flank pain, haematuria, hypertension or a smooth, palpable and often tender, subcostal or inguinal mass (11, 19-22). If the cyst is secondarily infected, fever, rigors, pain and malaise may also be found (23). Digestive symptoms, consisting of pains in the right subcostal area, abdominal distension, and vomiting, sometimes cause delay in the diagnosis, with a multitude of unnecessary radiologic examinations of the digestive tract. Occasionally, the cyst ruptures and the patient may suffer renal colic and pass typical 'grape-like' material in the urine. This is the so called hydaturia, which constitutes the only pathognomonic evidence of hydatid cyst and its rupture into the urinary tract (19, 24-28).
Confirmed isolated pelvic hydatid cysts are extremely rare (29). In most patients coexistent cysts are found elsewhere, especially in the liver. A retrovesical hydatid cyst causes symptoms by exerting pressure on the adjacent organs, including the bladder, seminal vesicles, vasa deferentia, and rectum. The main presenting features are difficulty in urination (30), hemospermia (31), and obstructive azoospermia (32). Therefore, a young man with urinary problems whose job is raising sheep or cattle, should be examined among others for possible hydatid cyst in the retrovesical region.
Retroperitoneal cysts are characterized the cysts located in the retroperitoneal space and have no communication with the adjacent organs. These cysts are rare even in endemic areas. An isolated retroperitoneal hydatid cyst could occur due to hematogenous dissemination after bypassing lung and liver or through a lymphatic route from intestinal vessels to the thoracic duct (33). Retroperitoneal cysts could present as a palpable mass or cause pain, while a large retroperitoneal cyst may produce renal obstruction (12).
Hydatid cysts involving the adrenals are usually secondary and part of generalized echinococcosis. The adrenal gland is involved in about 0,05% of all patients with echinococcosis (34, 35). Rarely, the echinococcal infection is limited to the adrenal gland. Only nine such primary hydatid cysts have so far been reported in the literature (36-39). Hydatid cysts make up only 6%-7% of all adrenal cysts (40). Adrenal cysts are generally silent lesions. They are usually found during autopsies or incidentally during surgery done for various abdominal pathologies. These cysts are mostly seen between 50-60 year old patients, are usually (92%) unilateral and show no special predilection for either side. There is no characteristic symptom complex associated with adrenal hydatid cysts. Symptoms depend on the compressing effect of the cyst and can be described as vague. They include flank discomfort, dull pain in the renal area, gastrointestinal disorders (belching, bloating, fullness, nausea, vomiting, flatulence, constipation and anorexia). Occasionally, a palpable mass may be present. The mass is usually round, firm but not tender. Sometimes adrenal echinococcal cyst may cause arterial hypertension which can be improved after ablation of the cyst (39). Acute abdominal pain or a tender mass may accompany intracystic hemorrhage, rupture, or infection. Anaphylactic shock may occur due to rupture of a hydatid cyst (5). Adrenal cysts may even be lethal if they are bleeding and not immediately diagnosed. It is thought that hemorrhage occurs secondary to trauma or some toxic or infectious process (41).
It has been suggested that approximately 80% of all pelvic hydatid disease involve the reproductive organs, the ovary being the most frequent location. In these cases, symptoms and signs are usually referable to local compression of the genital organs, urinary tracts, vascular and bony structures. Seminal vesicle involvement is extremely uncommon and only a few cases have been reported (31, 42-49). In most cases coexistent echinococcal cysts were found in other regions, especially in the liver. Such cysts produce symptoms when a space occupying effect on adjacent organs occurs. The presenting symptoms include voiding dysfunction (30), urinary retention (50), hemospermia (31), and azoospermia (32). Accidental detection is not infrequent.
In prostatic infection, the usual presentations are lower urinary tract symptoms and urine retention (15, 51). Hydaturia is a pathognomonic sign. The passage of grape like material in the urine derives from a connection between the cyst and urinary system.

Diagnosis and differential diagnosis
Laboratory control
As mentioned above, the clinical presentation of renal hydatid disease is heterogeneous. Diagnosis is only confirmed when scolices (grape skins) are present in the urine. Therefore, the establishment of diagnosis is based on the combination of clinical findings, imaging modalities, laboratory data and cytological information. Chemical tests include Casoni's which is accurate in 90% of cases and Ghedini-Weinberg which is 80% accurate (3). However, infection is not always detected and neither test is specific for this genus of parasites. Recently, many serological methods have replaced Casoni skin test to diagnose human hydatidosis. These methods include latex agglutination, indirect hemagglutination, counterimmunoelectrophoresis, enzyme-linked immunosorbent assay with whole hydatid fluid and with antigen 5, and a thermolabile lipoprotein that elicits the arc-5 precipitin line in immunoelectrophoresis (2). Indirect hemagglutination and enzyme-linked immunosorbent assay (ELISA) are the most sensitive tests but they also may provide false negative data. Eosinophilia is detected in 20-50% of patients (3, 20, 21).
Imaging control
A positive diagnosis is essentially based on radiologic examinations or screening methods. Findings in imaging studies are frequently suggestive of hydatid disease but usually inconclusive, and differentiation from a tumor or a complicated cyst may not be provided without surgery. Imaging findings in hydatid disease depend on the stage of cyst growth (ie, whether the cyst is unilocular, contains daughter cysts, or is partially or completely calcified [dead] ) (52, 53). A difference in attenuation and signal intensity between the fluid in the central portion of the cyst and that in the peripheral cyst constitutes a typical finding in echinococcosis due to a difference in content. A plain film may demonstrate a soft tissue mass in the kidney area with or without calcification (4, 21, 54). Peripheral curvilinear, 'eggshell' calcification usually indicates a benign lesion (50). Excretory urogram, nephrotomography, and retrograde pyelography reveal more, especially when there is communication between the cyst and the renal pelvis. Surraco (55) reported the 'bunch of grapes', 'crescent moon', and 'claw' signs as significant features although none is sufficient for a correct diagnosis. The 'bunch of grapes' sign is considered the most suggestive radiologic aspect, and shows the presence of daughter cysts (53).
Detection of daughter vesicles on ultrasound or CT is also characteristic of a hydatid cyst. Ultrasound is the initial diagnostic tool, since it is widely available, inexpensive and can detect typical unilocular or multilocular cysts in most of the cases (2, 56). Hydatid cysts are classified according to the ultrasonographic appearances described by Gharbi et al. (57). The multivesicular cyst, type III, is the most frequent and is highly characteristic of hydatid disease. The univesicular cyst with a detached or floating membrane (type II) is pathognomonic of the hydatid cyst.
CT appears to provide more information, and may be necessary for complicated cysts and in the differential diagnosis of renal cell carcinoma. Moreover, it provides a good description of residual parenchyma, shows a possible communication with the urinary tract and the presence of extrarenal disease as well. The useful diagnostic indicator as far as CT is concerned, is the CT density of daughter cysts which is lower than that of the mother cyst. In addition, percutaneous needle aspiration or needle biopsy along with contrast studies can be done. Percutaneous aspiration of cyst fluid, however, has been routinely discouraged due to the risk of anaphylactic shock reactions and dissemination of daughter cysts (2,53). Fine needle aspiration can be risk-free if performed with systemic albendazole therapy (58).
Ultrasonography and CT scan are the most valuable screening methods in the diagnosis of a retrovesical or retro-peritoneal hydatid cyst as well. As in renal echinococcosis, findings at imaging studies are usually inconclusive and a differential diagnosis may not be made without surgery (29). The differential diagnosis of a cystic retroperitoneal mass includes cystic lymphangioma, abscess, chronic haematoma, necrotic malignant soft tissue tumour and hydronephrosis. Malignant soft tissue tumours, retroperitoneal psoas abscesses or haematomas constitute lesions that arise from the loose retroperitoneal fat and can be described as partially cystic. Malignant fibrous histiocytoma is the most usual malignant soft tissue tumour in adults and its walls tend to appear thick and irregular. In case of psoas abscesses and organising haematomas, diagnosis is often suggested by the clinical history (59).
Adrenal hydatid cysts should be differentiated from other types of adrenal cysts. Among the real cysts the most common are endothelial cyst (45%) (haemangiomas and lymphangiomas); epithelial cysts are less common (9%) (glandular retention cyst, embryonal cyst). Another common type is pseudocysts (39%), which lack an epithelial lining and whose wall is well formed and fibrous. Pseudocysts can be caused by haemorrhage due to trauma or therapeutic anticoagulation, steroid therapy, traumatic delivery and pregnancy, and haemorrhage in a neoplastic adrenal lesion (40). US, CT and MRI can be useful in order to detect a hydatid cyst in the adrenal gland (39). The diagnostic sensitivity of US in abdominal echinococcosis ranges from 93% to 98%, while the sensitivity of CT is 97%. However, US is recommended to be the first choice because it is easy to perform and inexpensive. On CT scans, concentric areas of septation and calcification indicate that a cyst is of parasitic origin (60). At sonography the reflection produced by the retroperitoneal fat is displaced posteriorly by hepatic and subhepatic masses, and anteriorly by renal and adrenal masses. Wedging of this reflecting surface by a mass situated near the upper pole of the kidney indicates an adrenal origin (5). Laboratoty tests such as eosinophilia, Casoni test, and IHA are not diagnostic in adrenal hydatid cysts. There are many new sensitive and specific serological tests available, such as complement fixation, enzyme-linked immunosorbent assay, ARC 5 precipitation and specific hydatid IgE tests. Finally, the presence of calcification on plain abdominal films is strongly suggestive of a hydatid cyst or a pseudocyst. (5,61).
The first role in the diagnosis of echinococcal cysts involving the prostate and seminal vesicles plays CT in which the prominent feature of partial or total calcification of the cyst wall (49), US either abdominal or transrectal, is characteristically seen and MRI are of significant diagnostic value, as well. The differential diagnosis of pelvic echinococcosis includes congenital or acquired cyst of the seminal vesicles (parasitic, infectious or obstructive), cystic adenoma of the seminal vesicles, Mullerian duct cyst, cyst or diverticule of the vas deferens/ejaculatory duct, prostatic retention cyst, as well as primary retroperitoneal sarcoma, teratoma and leiomyoma.

Treatment
The optimum therapy and time to treat cystic hydatid disease should be individualized for every patient. Less than 10% of the cases are fatal but considerable morbidity can be expected if the disease is untreated (62, 63). The treatment of hydatid disease is surgical. Open surgery remains the first choice of treating renal hydatid cysts. Cyst removal without contaminating the patient is the aim of the therapy. Whether conservative or radical, cystectomy is performed first (64). Renal-conservation surgery is possible even for large lesions and should be intended when preoperative diagnosis of hydatidosis has been considered.
Cystectomy plus partial pericystectomy is the technique most often used. After discovery of the cyst, easily recognizable by its acrid yellow colour, the region is protected with sponges soaked in 2% formalin solution or hydrogen peroxide. The cyst is then punctured and aspirated before being filled with hydrogen peroxide or formalin solution for 5 minutes. This method reduces the internal pressure of the cyst, sterilizes the cystic content, and allows the second step, which is controlled opening of the cyst and its controlled evacuation with a spoon. Cystectomy is then performed. Removal of this cystic mass, transforms the operative field and renders the subsequent actions (pericystectomy or nephrec-tomy) more comfortable. After cystectomy, the cavity is covered with sponges soaked with 2% formalin solution or hydrogen peroxide (2,3). In its simplest mode, partial pericystectomy is carried out by removing the externalized part of the pericyst; this is the classic resection of the prominent dome. After resection of the dome, there is a clearage plane in the middle layer of the pericyst, through which a blunt dissection is feasible. Once the pericystectomy, partial or total, is achieved, the open calyx is sought so it can be closed.
Partial pericystectomy is indicated when the pericyst is supple or if bleeding occurs while the dissection is carried out. Total pericystectomy is indicated when the pericyst is dense or calcified.
Nephrectomy (25% of cases) must be reserved for destroyed kidneys that are the outcome of aged, open, and infected cysts (65). The initial practise of emptying and removing the cyst is helpful and serves to verify that the renal parenchyma is truly destroyed before performing nephrectomy. In fact, usually the diagnosis of hydatid disease of the kidney is made late, when the cyst is large and nephrectomy is the only possible surgical treatment. Small peripheral lesions are candidates for partial nephrectomy, particularly when diagnostic doubt persists or communication with the urinary tract is suspected. A nephrostomy tube may be essential in such cases. Total or radical nephrectomy is frequent when the preoperative diagnosis is not conclusive. Total nephrectomy is also electively performed for large lesions when the cyst results in tissue damage by pressure atrophy, and in cases with evident communication with the urinary tract. It is unknown whether the risk of implantation within the urinary tract and bladder justifies nephrouterectomy (66). Moreover, complications such as renal rupture, cyst hemorrhage and cyst infection are indications for total nephrectomy as well. Hydatid renal abscess also requires nephrectomy, as there is no accumulated experience to support others methods of management. When disease is exclusively renal, an incision above the 11th or 12th rib can be used to reach the upper pole. However, a bilateral and multiple organ disease requires a transperitoneal or thoracoabdominal approach. An unidentified renal mass is usually faced with radical nephrectomy, through a transperitoneal approach as well.
Percutaneous renal cyst puncture and aspiration has been performed previously but because of the associated risks the procedure is not an vogue (67). Authors underline that marsupialization of the renal hydatid cyst is not recommended unless the patient has only one kidney. In case of percutaneous therapy or marsupialisation of the renal hydatid cyst a medical treatment with albendazole should be given peri- and postoperatively to limit implantation at surgical spill (68). Moreover, pre-treatment with albendazole and praziquentel is very important as the cyst material becomes non-antigenic, decreasing the chance of anaphylaxis (3, 53). In addition, ethanol has been shown to be an effective scolicidal agent. Muellar et al were the first to report safe percutaneous drainage of hepatic hydatid cysts (69). Percutaneous drainage has many advantages over surgery, particularly in patients with a high surgical risk, recurrent disease or in patients with massive loss of renal parenchyma as a result of hydatid disease. This procedure decreases morbidity, hospital stay and renal loss. Experience with more patients is essential to standardize the method, while the need of pre-treatment requires further evaluation.
Finally, ex vivo renal surgery also has been carried out in some cases of hydatid cyst with central pole location. It is believed that a central hydatid cyst should not be manipula-ted in situ and that could be treated by en ex vivo operation, which achieves salvage of the kidney with the lowest risk for the patient. If an ex vivo operation is performed for other reasons the kidney is usually transplanted heterotopically into the groin rather than replanted orthotopically into the renal fossa (70).
Asymptomatic elderly patients may be left untreated, particularly when inactive disease is suspected based on changes in cyst volume and density, small size of the lesion that does not increase during follow up, complete peripheral calcification and a decrease in the title of specific immunoglobulin E. Of course, patient monitoring is totally required since there are no firm criteria form for parasite inactivation.
Although there is no effective medical therapy for hydatid disease, systemic treatment with antihelmintic agents, such as mebendazole or albendazole, have been widely used in the past. However, these agents do not always give satisfactory results and have deleterious side effects (18, 19). It has been proposed that these agents contribute to clinical improvement of the disease by diminishing the size of the cysts and preventing distal metastasis (53). The factors for success seem to be the ability of the drug to penetrate the cyst wall and the persistence of adequate levels of the active metabolites. Cysts in the brain or bone and multiple cysts can be treated with albendazole, especially when they are actively growing (71). Albendazole is a benzimidazole anthelmintic that is believed to be superior to mebendazole in treating hydatid disease due to better penetration and absorption. The usual dose is 10 to 15 mg/kg body weight daily or 400 mg twice daily for adults, given in cyclical fashion for 28 days with a 2-week drug-free interval between cycles. For most patients 3 cycles are sufficient. Overall cure rate is approximately 25%. The usual indications are inoperability, failure of medical therapy with mebendazole or recurrence. The drug can also be given perioperatively, perhaps with praziquantel, to limit implantation at surgical spill. Hepatotoxicity constitutes a severe side effect of albendazole and the medicine should be discontinued if liver function tests are elevated. In conclusion, however it must be stressed that medical management of the disease is far from being a realistic option to surgery and should be considered as adjuvant therapy or an alternative for poor surgical candidates.
For retrovesical hydatid cysts preoperative albendazole treatment decreases the viability of the cysts, but the duration of the treatment is controversial (29). On pelvic computed tomography, obliteration of the fatty tissue plane between the bladder and cyst may be accepted as a high index of suspicion for incomplete surgical excision. The surgical plan should take into consideration the patient's desire to preserve fertility. Cryopreservation of sperm should be offered to the patient before the operation when a complete excision of the retrovesical hydatid cyst is planned.
The treatment of retroperitoneal hydatid cyst is complete removal of the cyst without contamination of the field. If the cyst is closely adherent to the posterior abdominal wall muscles wide excision may be necessary to avoid rupture. The extraperitoneal approach is preferable in order to avoid intraperitoneal seeding. Injection of hypertonic saline into the cyst and irrigation of the solution into the retroperitoneum after the excision are also recommended. Other alternatives are the laparoscopic management and the aspiration.
Indications for surgery of adrenal cysts include large, complicated, parasitic and functioning cysts and neoplasms with cystic degeneration. Most authors recommend adrenalectomy for the treatment of hydatid disease (5, 37, 39, 72, 73). Access to the adrenal gland may be obtained by an anterior transabdominal or, for small lesions, by a posterior retroperitoneal traditional open approach. Recently, transabdominal laparoscopic and endoscopic retroperitoneal adrenalectomy have been performed with less morbidity and good results (74). Endoscopic removal of an adrenal hydatid cyst has not yet been reported. The operation of choice is removal of the cyst intact with preservation of the ipsilateral kidney and, if possible, the remaining adrenal gland, provided adequate haemostasis can be secured (39). If the cyst is large, meticulous aspiration and evacuation of its content may be necessary. With a laparoscopic approach, the risk of spillage of infectious material is higher.
The retrovesical approach through a midline subumbilical incision provides better exposure of pelvic cysts and minimizes the risk of puncture, comparably to the perineal and transvesical approaches. Additionally, preoperative administration of anthelminthic agents may further contribute in decreasing the parasite's viability. All patients should be followed postoperatively at regular intervals to detect local recurrence of the disease or subsequent involvement of other organs (75).
Recently, the first report of laparoscopic excision of a prostatic hydatid cyst has been presented.
Hydatid disease should be included in the differential diagnosis of space occupying lesions of the urinary tract at any age, especially in an endemic area. Accurate preoperative diagnosis sometimes renders feasible a renal preserving strategy. Prevention and control of the disease could be achieved if several health education measures are implemen-ted in the endemic zones. Such measures are mass chemotherapy of dogs with praziquantel, correct domestic dog-to-human contact and strictly supervised alimentary habits of domestic dogs.
Finally at as a real fact that a close follow up for these patients is absolutely necessary.

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