Hydatid Liver Disease in a Patient with Chronic Right Upper-Quadrant Abdominal Pain

Echinococcus granulosus

Hydatid disease of the liver is endemic in some areas of the world but is rarely encountered in the United States. The disease is usually caused by the parasite . Physicians who work within multicultural communities must be aware of this disease and its treatment. We present the case of a 35-year-old Mexican woman who complained of chronic right upper-quadrant pain. Computed tomography scanning revealed a ring-enhancing lesion within the right lobe of the liver, suggesting the diagnosis of a hydatid cyst. Following a course of antiparasitic therapy, the cyst was surgically removed. Six months later, the patient was pain free.

Guest Editor: H. Ralph Schumacher, Jr, MD,

Professor of Medicine, University of Pennsylvania School of Medicine, Philadelphia; Marie Crandall, MD, MPH, Assistant Professor of Surgery, Northwestern University; James A. Madura, II, MD, Assistant Professor of Surgery, Rush Medical College, Attending Surgeon, Cook County Hospital, Chicago, Ill

Case Presentation

A 35-year-old Mexican woman complained of chronic right upper-quadrant abdominal pain for the past 5 years. The pain was constant and dull, with radiation to the right leg and shoulder. She denied fever, chills, nausea, vomiting, night sweats, or change in bowel habits. Her medical history and review of systems were unremarkable.

The patient appeared well and was afebrile, with stable vital signs. Physical examination was unremarkable except for vague tenderness to palpation in the right upper-quadrant of her abdomen, but without a Murphy's sign or frank peritonitis. She had no jaundice or scleral icterus.

Laboratory test results were: leukocyte count, 6.9 x 10⁹/L, with a normal differential count; hemoglobin, 13.1 g/dL; platelet count, 241 x 10⁹/L; and normal serum electrolytes, liver enzymes, amylase, lipase, and coagulation profile. Urinalysis results were normal. An ultrasound of the right upper- quadrant of the abdomen was unremarkable. Computed tomography (CT) scans of the abdomen and pelvis demonstrated a ring-enhancing lesion within the right lobe of the liver in Couinaud's segment 6 (Figure 1). This led to a presumptive diagnosis of hydatid cyst. Her echinococcal antibody titer was within normal limits (0.399).

Albendazole (Albenza) therapy was initiated for 6 weeks, which resulted in some diminution of her discomfort.

After completing the course of the antiparasitic agent, the patient underwent surgical excision of the persistent cyst. Her abdomen was entered through a right subcostal incision. The cyst was readily palpable on the surface of segment 6, posterior and inferior. After mobilization of the right lobe of the liver, the area was packed with one-half strength sodium hypochlorite-soaked laparotomy pads. Using fine dissection and electrocautery, the cyst was enucleated from the liver (Figure 2). Intraoperative blood loss was 150 cc. The incision was closed with a single closed-suction drain in the cyst bed. Pathologic examination of the specimen revealed necrotic tissue within a calcified fibrinous capsule; no evidence of scolices or active disease remained.

The postoperative course was unremarkable. She was still pain free 6 months after surgery.

Discussion

Echinococcus

granulosus

E

multilocularis

Hydatid disease is most often caused by the parasite . By contrast, causes a rare form of the disease that is much more virulent and destructive, with hundreds of cysts invading the host. Humans are an incidental intermediate host in the organism's life cycle. The disease is endemic in certain areas of the world, particularly in Greece, North Africa, the Middle East, and South America. In these regions, echinococcosis is easily recognized, and physicians are readily able to deal with its complications. However, in the United States, lack of familiarity with the disease makes it a diagnostic and therapeutic challenge.

The life cycle of the echinococcus begins when the hermaphroditic adult worms embed in canine intestinal mucosa. The worm then replicates and sheds ova. The hardy eggs are shed with defecation and linger on the grass. Grazing animals, such as sheep or cattle, may then eat the infested grass, thus becoming the intermediate host. The parasite eggs lose their protective outer coat in the intermediate host's intestine, penetrate the mucosa, and enter the portal system. The majority are filtered by the liver sinusoids, but some enter the systemic circulation. Parasites can reach the lungs and peripheral organs. Wherever the eggs lodge, they transform into the larval form, also called the protoscolex, or scolex, creating a protective cyst where the organisms mature and replicate. The life cycle is completed when the host animal dies and carnivores eat the cyst-containing flesh. The scolices mature once again into adult worms in the gastrointestinal tract of the new host.

Humans are incidental intermediate hosts of the echinococcus. Once the egg has implanted and the larval stage begins, an interaction between host defenses and organism colony growth takes place, forming a cyst. Cysts grow over the course of months to years and are discovered when complications arise from soft tissue compression. A cyst is comprised of 2 distinct layers. The outer layer, or pericyst, is compressed, fibrosed tissue derived from normal surrounding parenchyma and a chronic inflammatory reaction. This zone is richly vascularized to provide nutrients to the cyst. The inner layer, called the laminated membrane, is a chitinous shell derived from the larvae. The cyst contains clear hydatid fluid and the germinative membrane where scolices reproduce. A scolex is not visible to the naked eye. It is about 150 ?m in length and has a mobile head; if set free from the cyst, it can implant on any nonepithelialized tissue in the body and create new cysts.

Patients with hydatid disease are often asymptomatic. Presenting complaints may be vague and difficult to interpret. Approximately 75% of hydatid cysts are found in the liver. Symptoms vary from a feeling of "fullness," to right upper-quadrant pain, to jaundice if compression of liver parenchyma compromises bile outflow. Physical examination findings are usually unremarkable. Infrequently, patients may present with peritonitis from intraabdominal rupture of the cyst. The cystic fluid occasionally causes an anaphylactic reaction. Cysts may develop in virtually any part of the body. Intracardiac,¹ intraaortic,² orbital,³ and many other locations have been reported. Brain cysts, which are rare, may cause headaches or seizures. Cysts in the lungs lead to chronic cough or dyspnea.

The diagnosis of hydatid disease requires a high index of suspicion. Laboratory studies are occasionally helpful. Eosinophilia is present about 30% of the time but is a nonspecific finding. Serologic studies are confirmatory in 60% to 90% of cases, depending on the assay used.^4,5 Plain radiographs are usually unrevealing for hepatic disease, but a chest x-ray is highly sensitive for pulmonary cysts and should be obtained in all patients. Occasionally, calcified lesions in the area of the liver will alert the physician to the possibility of hydatid disease. Ultrasound is sensitive for detecting mass lesions in the liver but is suboptimal for differentiating hydatid disease from other cystic lesions. Hydatid cysts have a pathognomonic appearance on a CT scan?a round, ring-enhancing, occasionally calcified lesion of homogenous density. Although CT-guided fine-needle aspiration to aid the diagnosis has been performed safely, it is not universally accepted, as the risk of spillage with peritoneal seeding or anaphylactic reaction cannot be totally avoided.^4,5 Hepatic cysts may obstruct or communicate with the biliary tract, causing jaundice or cholangitis. About 5% to 25% of patients develop symptoms mimicking biliary stone disease. Endoscopic retrograde cholangiopancreatoraphy may be helpful in diagnosing and treating these complications.⁶

The treatment of hepatic echinococcosis is primarily surgical. Several studies have indicated that a preoperative course of an antihelminthic agent, such as albendazole or mebendazole (Vermox), can decrease larval viability by the time of the surgery.^7,8 This may confer an advantage if there is inadvertent spillage during the operation, as well as improve the feasibility of laparoscopic cystectomy by decreasing the risk of spillage-related complications.

Not all cysts need to be excised. Small lesions deep in the hepatic parenchyma that would necessitate devitalization of large amounts of normal liver during removal and cysts located in hazardous positions should be left alone, unless they are causing significant symptoms or complications. Cysts with heavily calcified walls likely have undergone involution with scoliceal death and generally do not require excision unless the patient is symptomatic.^5,9 All other cysts should be removed to prevent rupture and spread. Patients who do not undergo surgical excision should be treated with scolicidal agents and followed with imaging studies to determine the stability of the cysts.

The standard operative approach to hepatic hydatid cysts is conventional open surgery. If the cyst is primarily above a sagittal plane at the level of the xiphoid, a thoracic approach with reflection of the diaphragm may be preferable. If the cyst lies below this plane, an abdominal or flank incision is usually adequate for exposure.^4,5 Once the abdomen is open and the cyst has been localized, either by palpation or ultrasound, the abdominal viscera are packed off with laparotomy pads soaked in a scolicidal agent to protect against the risk of dissemination should spillage occur. Agents used include 0.16% sodium hypochlorite, hypertonic saline (solution >15%), and 0.05% silver nitrate.^5,10 The cyst is then evacuated and debrided from surrounding tissue. If the cyst is superficial and readily accessible, a pericystectomy, or enucleation, may be performed by dissecting around the cyst.¹¹ This must be done with caution, as this area may contain large vascular structures. The remaining liver should be examined intraoperatively by palpation or ultrasound to ensure that there are no other adjacent cysts.^4,5

Several methods can be used to manage the hepatic defect. The opening can be sutured closed or marsupialized to the peritoneal cavity, a viable flap of omentum can be secured within the pericystic defect, or the cavity can be closed over drains. These approaches appear to have equivalent outcomes.^4,5

Several large series have been published from endemic areas that describe a minimally invasive approach to hydatid cystectomy.^12,13 Laparoscopic treatment appears to be both feasible and safe in properly selected patients. The technique utilizes cystotomy with partial cystectomy and drainage in most cases.

E multilocularis

Major hepatic resection has been used for the removal of cysts but should be reserved for patients with multiple cysts confined to a particular lobe or segment and for those with infection.¹⁴

Complications of cystectomy include biliary fistulae (5%-25%), cholangitis (5%-30%), infection of the residual cavity (10%-50%), and complications common to any celiotomy procedure with general anesthesia. Surgical treatment of hepatic hydatid cysts carries an overall mortality rate is less than 1%. The recurrence rate is approximately 7%.^4,5

Patients who are unacceptable surgical risks or who have complex cysts not amenable to surgical excision are treated with longterm antihelminthic therapy, with success rates ranging from 30% to 70% for symptom regression.⁵ Such patients may be candidates for percutaneous drainage.

Public health agencies are trying to educate people in endemic areas about the parasite and its transmission. Preventive measures, such as not feeding slaughtered livestock to dogs or empiric treatment of dogs with praziquantel (Biltricide), have decreased the incidence of echinococcosis.¹⁵ There has been some success in decreasing the spread of the parasite by administering anti-echinococcal vaccines to sheep.¹⁶

Conclusion

Hydatid disease of the liver is endemic in some areas of the world and is rarely encountered in the United States, but as our communities become more international, its prevalence may increase. Physicians who work within multicultural and international communities must be aware of this disease entity and its attendant morbidities.

Ann Thorac Surg

1. Birincioglu CL, Bardakci H, Kucuker SA, et al. A clinical dilemma: cardiac and pericardiac echinococcosis. . 1999;68:1290-1294.

Radiology

2. Men S, Yucesoy C, Edguer TR, et al. Intraaortic growth of hydatid cysts causing occlusion of the aorta and of both iliac arteries: case report. . 1999;213:192-194.

Ann Plast

Surg

3. Zaidi M. An unusual case of orbital hydatid cyst: a surgical emergency. . 1999;42:327-329.

J Hepatobiliary Pancreat

Surg

4.Erdem E, Nessar M, Sungertekin U, et al. The management of hepatic hydatid cysts: review of 94 cases. . 1998;5:179-183.

Arch Surg

5. Balik AA, Basoglu M, Celebi F, et al. Surgical treatment of hydatid disease of the liver: review of 304 cases. . 1999;134:166-169.

J Clin Gastroenterol

6. Ozaslan E, Bayraktar Y. Endoscopic therapy in the management of hepatobiliary hydatid disease. . 2002;35:160-174.

Eur J Surg

7. Turkcapar AG, Ersoz S, Gungor C, et al. Surgical treatment of hepatic hydatidosis combined with perioperative treatment with albendazole. . 1997;163:923-928.

Eur J Gastroenterol

Hepatol

8. Aktan AO, Yalin R. Preoperative albendazole treatment for liver hydatid disease decreases the viability of the cyst. . 1996;8:877-879.

HPB Surg

9. Prousalidis J, Tzardinoglou E, Kosmidis C, et al. Surgical management of calcified hydatid cysts of the liver. . 1999;11:253-259.

HPB Surg

10. Besim H, Karayalcin K, Hamamci O, et al. Scolicidal agents in hydatid cyst surgery. . 1998;10:347-351.

G

Chir.

11. Amicucci G, Sozio ML, Sozio A, et al. Hydatid cysts of the right lobe of the liver treated with total pericystectomy using a transparenchymal approach [in Italian]. 1998;19:49-50.

J Laparoendosc

Adv Surg Tech A

12. Chowbey PK, Shah S, Khullar R, et al. Minimal access surgery for hydatid cyst disease: laparoscopic, thoracoscopic, and retroperitoneoscopic approach. . 2003;13:159-165.

Dig Surg

13. Ertem M, Uras C, Karahasanoglu T, et al. Laparoscopic approach to hepatic hydatid disease. . 1998;15:333-336.

Hepatogastroenterology

14. Alfieri S, Doglietto GB, Pacelli F, et al. Radical surgery for liver hydatid disease: a study of 89 consecutive patients. . 1997;44:496-500.

Echinococcus granulosis,

Taenia ovis,

T hydatigena. Parasitology

15. Lawson JR, Roberts MG, Gemmell MA, et al. Population dynamics in echinococcosis and cysticercosis: economic assessment of control strategies for and . 1988;97:177-191.

Int J Parasitol

16. Lightowlers MW, Jensen O, Fernandez E, et al. Vaccination trials in Australia and Argentina confirm the effectiveness of the EG95 hydatid vaccine in sheep. . 1999;29:531-534.

Commentary

Marcia Mitre, MD, Attending Physician, Gastrointestinal Division, Department of Medicine, Allegheny General Hospital, Pittsburgh, Pa; Kyong-Mi Chang, MD, Assistant Professor, Gastrointestinal Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pa

E granulosus

E multilocularis

Crandall and Madura present an interesting case of a Mexican woman with a hepatic cyst caused by a parasite that is not often seen in the United States. Human echinococcosis is caused by accidental ingestion of the tapeworm or eggs that hatch and migrate to visceral organs, most frequently to the liver. Echinococcal disease is seen worldwide but is uncommon in the United States, where it is identified mostly in immigrants from endemic countries. Diagnosis requires a high index of suspicion based on epidemiologic information and clinical findings and is confirmed by radiographic detection and serology. Clinical presentation is often nonspecific, depending on the location and size of the cyst, but can include right upper-quadrant discomfort with hepatomegaly as well as cholestatic jaundice, cholangitis, portal hypertension, and even Budd-Chiari syndrome. Rarely, patients present with peritonitis or an anaphylactic reaction caused by the ruptured cyst.

E granulosus

E

multilocularis

Cysts larger than 10 cm in diameter are more symptomatic than smaller ones. causes less symptomatic disease than . Characteristic radiographic findings include cysts in the right lobe of the liver, with internal septation as a result of daughter cysts; floating "hydatid sand" seen on ultrasound (90%-95% sensitivity); as well as calcified ring-enhancing cysts revealed on a CT scan (95%-100% sensitivity). Magnetic resonance imaging is generally not necessary, except in complicated cases.

granulosus

E multilocularis.

Serologic tests (most often indirect hemagglutination and ELISA) provide further confirmation. However, as in the case presented here, normal echinococcal antibody titer does not exclude the diagnosis, perhaps because of a weak immune response that results in false-negative results. Positive serology may be found in up to 80% to 94% of patients with conventional tests. An indirect immunofluorescence assay shows good sensitivity, with a positive response in 95% of patients with hepatic hydatid cysts.¹ Serologic testing may differentiate between antigenic components of E and Microscopy of the cyst contents may demonstrate the presence of the parasite, but it did not in this report. More specific molecular methods (ie, polymerase chain reaction, Southern blot) can further enhance diagnosis.

E granulosus

E multilocularis

E granulosus

E multilocularis

Direct surgical removal is the treatment of choice in most patients. Adjunctive mebendazole or albendazole chemotherapy is recommended to reduce the risk of secondary hydatidosis caused by spillage of cystic contents (before and after surgery for and after surgery for ). Duration of chemotherapy varies from 1 month with albendazole and 3 months with mebendazole for to a minimum of 2 years of albendazole therapy for . Another approach gaining popularity is the PAIR procedure (Percutaneous Aspiration, Injection of scolicidal agent, and Reaspiration). Scolicidal agents (eg, hypertonic saline or ethanol) are injected with ultrasound guidance, and albendazole or mebendazole is administered before and after the procedure.^2-4 Patients not suitable for surgical or percutaneous therapy may be managed with chemotherapy alone (albendazole or mebendazole). Treated patients may be monitored by radiographic studies (eg, ultrasound) and serology, as well as other relevant clinical parameters (eg, liver function tests). As the authors note, it is important for physicians to be familiar with diagnostic findings and treatment options for hepatic hydatid cyst.

World J

Surg.

1. Biava MF, Dao A, Fortier B. Laboratory diagnosis of cystic hydatid disease. 2001;25:10-14.

Radiology

2. Acunas B, Rozanes I, Celik L, et al. Purely cystic hydatid disease of the liver: treatment with percutaneous aspiration and injection of hypertonic saline. . 1992;182:541-543.

AJR Am J

Roentgenol

3. Men S, Hekimoglu B, Yucesoy C, et al. Percutaneous treatment of hepatic hydatid cysts: an alternative to surgery. . 1999;172:83-89.

AJR Am J

Roentgenol

4. Ustunsoz B, Akhan O, Kamiloglu MA, et al. Percutaneous treatment of hydatid cysts of the liver: long-term results. . 1999;172:91-96.