Echinococcosis in a non-endemic country – 20-years’ surgical experience from a Norwegian tertiary referral Centre

Abstract

Background

In Scandinavia, the incidence of cystic echinococcosis (CE) and alveolar echinococcosis (AE) is low and almost exclusively an imported disease following the trends of immigration. The aim of the study was to review available data on clinical management and outcome for patients treated at Oslo University Hospital, a referral centre for echinococcosis in Norway, with special emphasis on surgical treatment.

Methods

All patients admitted with echinococcosis between January 2000 and December 2020 were identified. Medical records were reviewed retrospectively concerning patient demographics, treatment strategy, surgical procedures, complications and outcomes.

Results

A total of 92 patients with median age 37 years (range 4-85) were identified. Sixty-eight patients (74%) were symptomatic. All patients, except for two, were immigrants to Norway and born in endemic areas. Ninety patients were diagnosed with CE and two with AE. Location of the cysts was most commonly in the liver (86%) followed by peritoneum, lungs, and spleen. All patients with active cysts were treated with albendazole. Surgical treatment was performed in 51 (56%) patients. The most common reason for abstaining from surgical treatment was that the diagnostic work-up revealed inactive cysts or interventional radiology was performed. Of the 51 patients who underwent surgery, a radical procedure was performed in 32 (64%) cases, a conservative procedure in 12 (24%), and a combination in six (12%). Clavien Dindo grade ≥3 complications occurred in 30%, and 90-day mortality was 2%. Bile leakage occurred in seven patients and was treated successfully with endoscopic retrograde cholangiopancreatography with biliary stent placement in all patients.

Conclusion

In a low-endemic area like Norway, management of echinococcus includes medical therapy, surgery, and/or interventional radiology. Surgical intervention seems to be effective, and is associated with acceptable morbidity rates.

Keywords:

• Echinococcosis; non-endemic; surgical treatment; treatment outcome

Introduction

Echinococcosis in humans occurs as a result of infection by the larval stages of taeniid cestodes of the genus Echinococcus. Echinococcus granulosus sensu lato causes cystic echinococcosis (CE), a chronic cyst-forming disease [1,2]. E. multilocularis causes alveolar echinococcosis (AE), in which the larval mass resembles a malignancy in appearance and behaviour, and proliferates indefinitely by exogenous budding and invades the surrounding tissues. CE occurs worldwide in sheep-raising areas including Africa, the Mediterranean region of Europe, the Middle East, Asia, South America, Australia, and New Zealand [1]. Conversely, AE is primarily endemic in northern latitudes where wild foxes and coyotes act as principal hosts. The incidence of echinococcosis is very low in the Scandinavian countries and is almost exclusively seen as imported cases [3,4].

In principle, all tissues can be affected in echinococcosis. The liver is the most commonly affected organ in 70% of cases, followed by the lungs in about 20% and remaining organs in about 10% (kidney, brain, bone, muscles and others) [5]. Treatment modalities in CE can be surgery (radical or conservative), medical (benzimiadazoles), percutaneous techniques (as Puncture, Aspiration Injection, and Re-aspiration (PAIR)) for hepatic cystic echinococcosis, or a watch-and-wait strategy [5,6]. Diagnostic or therapeutic percutaneous intervention or surgery should be performed together with periinterventional chemoprophylaxis. The choice of treatment strategy is based on the WHO-IWGE cyst classification where cysts are classified as active, transitional and inactive with subsequent classification into subgroups requiring different treatment strategies [7]. In AE, the therapeutic options are fewer, and surgical resection of the entire larval mass, usually by excision of the entire affected lobe of the liver, is desired in combination with long-lasting medical therapy. In some cases radical surgery is not possible and prolonged suppressive anti-parasitic therapy remains the only option.

There are two principal surgical approaches for hepatic echinococcosis; radical (resection of the cyst) and conservative (evacuation of the cyst content and partial removal of the cyst capsule). Radical procedures include total pericystectomy, or liver resection in case of liver cysts or lung resection in case of lung cysts. Conservative procedures refer to techniques such as endocystectomy, external drainage, deroofing of the cyst wall and extraction of the parasite, deroofing of the cystic cavity and closure by capitonnage without drainage, omentoplasty and drainage of the cystic cavity, partial pericystectomy (leaving a large piece of cyst wall deeply sited within the liver), cyst marsupialization with external drainage and cystojejunostomy, or subtotal pericystectomy [8]. To take care of the residual cavity, if possible, an omentoplasty is performed by inserting a plug of the greater omentum fixed at the margin of the cyst wall.

Oslo University Hospital (OUH) is a referral center for echinococcosis in Norway (population 5.3 million). The aim of the study was to review available data on treatment modality and outcome for patients treated for echinococcosis at OUH during a 21-year period, with special emphasis on surgical treatment of hepatic disease.

Methods

This is a retrospective review of all patients admitted to OUH with echinococcosis between January 2000 and December 2020. The hospital database was screened to identify all cases with International Classification of Diseases 10 (ICD‐10) codes B67.0-B67.9. All medical records were reviewed concerning the following parameters: age, gender, country of origin, clinical presentation, location and type of cysts diagnosed by radiologic imaging, treatment, postoperative morbidity, hospital stay, and outcomes. The diagnosis of echinococcosis was in most cases confirmed by positive serology (Swedish Institute for Infectious Disease Control, Stockholm, Sweden), by microscopy and/or PCR of cyst fluid, or by histological examination of the surgical specimen. Radiologic workup included ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI). Surgery, medical treatment, and PAIR were all available treatment options for CE in this time-period. All patients were initially evaluated by infectious disease specialists followed by an interdisciplinary discussion with interventional radiologists and hepatobiliary surgeons. The Hospital Review Board approved the study (20/09690) according to the general guidelines provided by the Regional Ethics Committee.

Surgical treatment was the preferred treatment approach if not the cyst was classified as inactive, deemed technically inoperable, was suitable for PAIR using ethanol or hypertonic saline, or the patient had contraindications for surgery due to high age or comorbidity. The procedures performed depended on the size, location and type of the cyst(s) and the general condition of the patient. For liver cysts located peripherally, if feasible, radical management by simultaneous removal of the pericyst was performed. The cyst was removed en-bloc with the pericyst, thus avoiding intraoperative spillage by accidental rupture. For large cysts located deeper in the liver parenchyma partial or total cystectomy was performed. In all patients, the pericystic area and operating field were covered with sponges soaked with 20% hypertonic saline. If the cyst was opened, the cyst was punctured and as much fluid as possible was aspirated to prevent dilution of the scolicidal agent. Then, 20% hypertonic saline was instilled into the cyst cavity in a volume equal to the amount aspirated. After 10 min, the cyst fluid was aspirated again. In partial pericystectomy the anterior wall of the cystic lesion was removed as widely as possible. All the components of the cyst were removed from the interior. Any biliary communications with the cyst were sutured individually. In partial cystectomy, omentoplasty was performed at the surgeon’s discretion and the prepared omental pedicle was fixed into the cystic cavity with an absorbable suture. One drain was placed in the operated area at the surgeon’s discretion. All patients received medical treatment with antihelmintic (primarily albendazole) for 3-6 months postoperatively.

Results

A total of 92 patients were admitted with echinococcosis during the study period. Median age was 37 years (range 4-85), and 50 patients (54%) were female. Sixty-eight patients (74%) presented with symptoms. All but two patients were immigrants to Norway and born in endemic areas. Location of the cysts was most commonly in the liver followed by peritoneum, lungs and spleen (Table 1). With the exception of two cases with AE, all patients had CE.

Table 1. Characteristics of patients with cystic echinococcosis (n = 90) and alveolar echinococcosis (n = 2), Oslo University Hospital, 2000–2020.

	Overall	Surgical treatment (n = 51)	Non-surgical treatment (n = 41)
Age, years (range)	37 (4–85)	34 (4–74)	39 (7–85)
Gender
Male	42	21	21
Female	50	30	20
Region of origin
Norway	2	1	1
Central and Eastern Europe	23^a	13	10
Northern Africa	7	2	5
Eastern Africa	7	6	1
Central Asia	4	2	2
Western Asia	34	17	17
Southern Asia	15	10	5
Symptoms and signs
Abdominal pain/discomfort	56	39	17
Chest pain	2	1	1
Dyspnoea	4	2	2
Other	6	5	1
Asymptomatic	24	4	20
Localization of cysts
Liver	67^a	35	32
Lung	6	2	4
Liver + lung	5	2	3
Liver + peritoneum	7	6	1
Peritoneum	3	3	0
Spleen	2	2	0
Small bowel	1	1	0
Urinary bladder	1	0	1
WHO classification of CE cysts of the liver
CE1	10	5	5
CE1 + CE2	1	1	0
CE1 + CE2 + CE3	1	0	1
CE1 + CE3A	1	0	1
CE2	16	12	4
CE3A	8	8	0
CE3B	18	16	2
CE4	13	7	6
CE4 + CE5	2	0	2
CE5	22	2	20

^aIncluding 2 patients resected for E. multilocularis.

Forty-one (45%) patients, all with CE, received non-surgical treatment only. The reasons for choosing a watch-and-wait strategy, medical treatment or PAIR are given in Table 2. Twelve of these patients had previously undergone surgical treatment for CE (liver; n = 6, lung; n = 3, liver and lung; n = 3) before year 2000 in their country of origin (n = 11) and Norway (n = 1). Thirteen patients underwent PAIR.

Table 2. Reasons for abstaining from surgical treatment (PAIR, chemotherapy or watch and wait) (n = 41).

Reason	Number
Inactive cyst(s)	27
Technically inoperable	4
PAIR	6
Other	4
Age/comorbidity	1
Lost for follow-up (asylum seeker)	1
Patient preference	2

PAIR = puncture, aspiration, injection, and re-aspiration.

Surgical treatment was performed in 51 patients (56%), of whom 49 had CE and two had AE. One patient underwent surgery at another Norwegian hospital and was excluded from analysis of surgical outcomes. A radical procedure was performed in 32 (64%) patients (including both patients with AE), a conservative procedure in 12 cases (24%), and a combination was performed in six patients (12%) (Table 3). Twelve of these patients had earlier undergone surgical treatment for CE (liver; n = 9) in Norway (n = 4) or in their country of origin (n = 8). Two of these patients had undergone laparoscopic deroofing of a splenic cyst and a liver cyst, respectively, incorrectly diagnosed as simple cysts. Seven patients were previously treated with PAIR at OUH. Details on surgical procedure and additional organs resected are shown in Table 3. In 15 patients undergoing total or partial pericystectomy, omentoplasty was performed.

Table 3. Surgical procedures and complications in 50 patients undergoing surgical treatment for cystic echinococcosis at Oslo University Hospital.^a

Type of procedure	Number	Complications (Clavien Dindo)	Postoperative bile leak	Comments
Radical procedures n = 32
Liver
Total pericystectomy (cholecystectomy in two cases, omentoplasty in four cases)	10	–	–	–
Segment resection (resection of peritoneal cyst in two cases, cholecystectomy in one case)	8	2 (CD 3)	2	Bile leak in both patients
Wedge resection	2	1 (CD 3)	–	Liver abscess/pleural effusion/ pneumothorax
Right hemihepatectomy (resection of peritoneal cyst in one case, right adrenal gland/caval vein resection in one case)	3	2 (CD 3)	1	-Bile leak/intraabdominal abscess/pleural effusion -Pleural effusion
Other organs
Resection of peritoneal cyst (hemicolectomy in one case)	3	–	–	–
Splenectomy	2	–	–	–
Pulmonary resection	3	1 (CD 3)	–	–Bronchopleural fistula
Small bowel resection	1	–	–	–
Conservative procedures n = 12
Partial pericystectomy (liver) (cholecystectomy in four cases, omentoplasty in nine cases, resection of peritoneal cyst in one case)	12	4 (CD 3)	4	Bile leak in all four patients
Combined procedures n = 6
Segmentectomy (liver) + Partial pericystectomy (omentoplasty in one case)	3	3 (CD3 in two cases, CD 5 in one case)	–	-Bile duct injury -Liver abscess, pulmonary embolism -Myocardial infarction/death
Segmentectomy (liver) + Resection of multiple peritoneal cysts	1	1 (CD 4)	–	-Severe hypernatremia
Right hemihepatectomy + Partial pericystectomy + omentoplasty	1	1 (CD 4)	–	-Acute renal and respiratory failure, haemolytic uremic syndrome
Resection of peritoneal cyst + PAIR liver (performed during the same procedure)	1	–	–	–

^aOne additional patient underwent surgery at another Norwegian hospital and was excluded from analysis of surgical outcomes.

PAIR = puncture, aspiration, injection, and re-aspiration, CD = Clavien Dindo.

For the 51 patients who underwent surgical treatment, the median hospital stay was eight days (range, 3-75). Clavien Dindo grade ≥3 complications occurred in 30% (Table 3). There was one postoperative death (2%) within 90-days due to a myocardial infarction. Bile leakage occurred in seven patients and was treated successfully in all patients with endoscopic retrograde cholangiopancreatography (ERCP) and biliary stent placement. A minor bile duct injury detected intraoperatively occurred in one patient and was treated with primary suture, and postoperatively ERCP with biliary stent. One patient developed severe acute hypernatremia, detected immediately postoperatively, caused by intraoperative peritoneal lavage with 20% hypertonic saline due to cystic fluid spillage. Clavien-Dindo grade ≥3 complication occurred in 18.8%, 33.3%, and 83.3% in patients treated with radical surgery, conservative surgery, and combined surgery, respectively (Table 3). Follow-up was for most patients performed at their primary hospitals elsewhere in Norway. To the best of our knowledge, no cases were readmitted with relapse after surgical treatment.

Discussion

This singe-centre study assessed the management and surgical outcome of patients with echinococcosis during a 21-year period in a non-endemic country. Surgery was the treatment of choice in 56% of the patients. A radical surgical procedure was performed in 64% of the operated patients, a conservative surgical procedure in 24%, and a combination of a radical and conservative procedure in 12%. Surgical treatment had a morbidity rate of 30% and a 90-day mortality rate of 2%. The most common cause for abstaining from surgical treatment was that the diagnostic work-up revealed an inactive cyst (WHO CE4 or CE5).

Surgery and peri-interventional chemoprophylaxis remain the only definitive treatment for large, active, symptomatic or complicated CE in the liver, i.e. cysts with daughter cysts (stage CE2) and cysts with daughter cysts in solid matrix (stage CE3B) [7]. Both radical and conservative surgery for hepatic cystic echinococcosis may be performed [8,9]. Radical procedures are considered safe and effective, especially at high-volume HPB surgical centres, because they are associated with low morbidity and mortality rates. Moreover, the recurrence rate is reduced almost to zero. However, conservative surgery avoids the undue sacrifice of healthy liver parenchyma and is preferred to hepatic resection if possible [10]. In our series, postoperative complications occurred in 30% of the patients, and postoperative mortality was 2%, with the lowest complication rate (18%) in the group receiving radical surgery. In a meta-analysis, postoperative morbidity and mortality of conservative versus radical procedures were 19.0% vs 17.7% and 0% vs 0.8%, respectively [8]. As shown in other reports bile leak was the most common postoperative complication and occurred in seven cases [8–10]. In patients with biliary fistula output that is high or does not decrease within the first postoperative week early ERCP is recommended [11]. In this series, ERCP was performed early in all cases and the success rate was 100%.

In Scandinavia the incidence of echinococcosis is low and considered to be almost exclusively an imported disease. All besides two patients in the current study were immigrants to Norway and were infected in their country of origin. The two patients of Norwegian ethnicity: one elderly patient who developed cystic echinococcosis in the lungs during a longer stay in Eastern Asia several decades ago, and one younger patient with unknown route of transmission who was diagnosed with hepatic CE. Of note, the latter patient had earlier undergone a laparoscopic deroofing of a liver cyst incorrectly diagnosed as a ‘simple’ liver cyst. Two years later the patient was re-admitted with multiple liver and peritoneal cysts, and Echinococcus serology was positive. Thus, echinococcosis must be considered in the differential diagnosis of liver or lung cyst also in ethnical Scandinavian patients.

It is reported that rupture of hydatid cyst (spontaneous or iatrogenic) can lead to anaphylaxis [12,13]. Although this is a rare complication, there should always be awareness about this during surgery of hydatid disease [14]. No treatment-related anaphylactic reactions were identified in our cohort, but one case of severe hypernatremia was diagnosed immediately postoperatively. The hypernatremia was caused by peritoneal lavage with hypertonic 20% saline in a patient with multiple peritoneal and liver cysts [15]. Numerous solutions, such as hypertonic saline solution (15-30%), formalin (2%), silver nitrate (0.5%), povidone-iodine (10%), chlorhexidine (0.05%), and a combination of cetrimide (0.5%) and chlorhexidine (0.4%) have been used as scolicidal agents for the purpose of inactivation [16,17]. However, there is no consensus on which is the best and safest agent. Scolicidal agents used in PAIR are mainly hypertonic 20% saline or 95% ethanol [7]. However, injection of scolicidal solutions should be avoided into cysts that communicate with the biliary or bronchial tree [5]. Some authors consider that hypertonic saline is not appropriate for peritoneal lavage because it may damage the peritoneal surfaces and may cause hypernatremia [18,19]. The severe and potentially lethal hypernatremia that developed in one patient in this series, demonstrates that irrigation with hypertonic 20% saline should be used with great caution [19].

In conclusion, human echinococcus is rare in Norway. Management is based on radiological staging of the cysts and can include medical therapy, surgery, or interventional radiology. Surgical intervention is effective, and associated with acceptable morbidity rates.

Acknowledgements

Thanks to Dr Tore Lier, Public Health Agency of Sweden and National reference laboratory for parasite serology at University Hospital of North Norway for performing Echinococcus serology. We appreciate the pioneer work by professor emeritus Bjørn Myrvang and Dr Arild Maeland in establishing treatment options for patients with cystic echinococcus at Oslo University Hospital.

Disclosure statement

No potential conflict of interest was reported by the author(s).