Hydatid disease of liver

Presentation for seminar MBBS

1. Hydatid disease of liver Roll no 0954

2. History Hydatid disease is one of the oldest diseases known to man. It was first described in the Talmud as a " Bladder full of water " . Hippocrates described the human hydatid disease more than two thousand years ago with a very interesting expression ( liver filled with water ) .

3. Al- Rahzes wrote detailed script on hydatid cyst of the liver about one thousand years ago . 17th century - Francisco Redi illustrated that the hydatid cysts of echinococcosis were of “animal” origin Early to mid 1900s , the more distinct features of E. granulosus and E. multilocularis 1928 - The exact life cycle of the parasite was recognized by Dew et al.

4. Hydatid : Greek for ‘drop of water’ Echinococcus : ‘hedgehog berry’ coined by Rudolphi in the first decade of the 19 th century

5. Echinococcosis / hydatid disease is a parasitic disease that affects both humans and other mammals, such as sheep, dogs, rodents and horses. Echinococcus granulosus - cystic echinococcosis / unilocular echinococcosis , dog tapeworm Echinococcus multilocularis - alveolar echinococcosis /alveolar colloid of the liver/ alveolar hydatid disease/ alveolococcosis / multilocular echinococcosis , “small fox tapeworm” Echinococcus vogeli - polycystic echinococcosis / human polycystic hydatid disease/ neotropical echinococcosis Echinococcus oligarthus - polycystic disease rarely.

6. Epidemiology E. granulosus is present virtually worldwide, more common in sheep and cattle raising countries. South America, North Africa, Eastern Australia, Asia and sporadically in the Middle East, Mongolia, Eastern Europe and the UK. India - AP, Gujarat, Tamil Nadu, West Bengal, Orissa, Bihar, Punjab, Haryana, HP, UP, Kashmir, Delhi and Pondicherry. E. multilocularis -Northern hemisphere, including central Europe and the northern parts of Europe, Asia, and North America. E. vogeli and E. oligarthus -Central and South America.

7. (< 1 case per 1 million inhabitants) in the continental United States. CE in endemic areas ranges from 1-220 cases per 100,000 inhabitants, Sex No sexual predilection. Age The cysts grow slowly ( 1-3 cm / year ), and rarely diagnosed during childhood or adolescence unless the brain is affected. CE is a disease of younger adults, with an average age at diagnosis of 30-40 years. AE is a disease of older adults, with an average age at diagnosis of older than 50 years.

8. Morphology Adult worm : 3-6 mm Scolex - pyriform 300 µm, 4 suckers and a protrusible rostellum with two circular rows of hooklets Neck - short, thick Strobila - 3 segments usually (immature, mature and gravid)

9. 32-36 µm length, 25-32 µm breadth Hexacanth embryo/ oncosphere with 3 pairs of hooklets . Passed through the faeces of the definitive host and it is the ingestion leads to infection in the intermediate host. Egg:

10. Larva: within hydatid cyst

11. Hosts Definitive hosts E. granulosus : dogs and other canidae E. multilocularis : foxes, dogs, other canidae and cats E. vogeli : bush dogs and dogs E. oligarthus : wild felids Intermediate Hosts E. granulosus : sheep, goats, swine and other wild herbivores E. multilocularis : small rodents E. vogeli : rodents E. oligarthus : small rodents Humans - dead end

12. Life cycle

13. Incubation period Months to years or even decades. Largely depends on the location of the cyst in the body and how fast the cyst is growing.

14. Pathogenicity Hydatid cyst represents larval form Generally acquired during childhood. Gradual displacement of vital host tissue, vessels or parts of organs → damage and dysfunction The cyst wall is formed by: Pericyst - fibrous tissue laid down by host fibroblasts and new blood vessels. merges with surrounding normal tissue. Nutrition derived through this layer. In old cysts, it may become sclerosed or calcified and parasite may die within it. Absent in lung, bone, muscle, sometimes brain

15. Ectocyst : Secreted by embryo Tough, acellular , laminated ,elastic hyaline membrane, 1 mm Resembles white of a hard boiled egg When excise or ruptured, it curls on itself exposing the inner layer Non- infective Endocyst : Germinal layer, 22-25 µm thick Consists of number of nuclei embedded in a protoplasmic mass. Gives rise to ectocyst , brood capsules and scolices Secretes hydatid fluid.

16. Echinococcus multilocularis - Multilocular cysts Cyst spreads from the outset by actual invasion rather than expansion. May be mistaken for malignant tumour . Destruction of parenchyma may cause hepatic failure. Spread by extension, lymphatic or hematogenous Among the most lethal of helminthic infections If untreated, 70% progress to death

17. Hydatid fluid Clear, colourless or pale yellow. Specific gravity= 1.005-1.010 Slightly acidic , pH 6.7 Contains sodium chloride, sodium phosphate and sodium and calcium salts of succinic acid. Antigenic, used for Casoni’s test Anaphylactic shock on absorption Centrifuged deposit shows hydatid sand – brood capsules, free scolices and hooklets .

18. Organs affected The parasite can colonise virtually every organ in the body Liver- 52-77% (¾ right liver) Lung- 8.5-44% Abdominal cavity- 8% Kidney- 7% Central nervous system- 0.2-2.4% Bone- 1-2.5% Less common- spleen, bladder, thyroid, prostate , heart, eye, adrenal gland, cervix, fallopian tube, ovaries, breast, pancreas, subcutaneous tissues .

19. Clinical features History : of living in or visiting an endemic area must be established. Exposure to the parasite through the ingestion of foods or water contaminated by the feces of a definitive host must be determined. Contact with infected dogs

20. disease may be asymptomatic (75%) and discovered coincidentally at post mortem or when an ultrasound or CT scan is done for some other condition. Most symptomatic cysts ≥ 5 cm Depends on site, size, parasite load Symptomatic disease presents with a swelling causing pressure effects.

21. Dull pain from stretching of the liver capsule. Palpable or visible abdominal mass . Chronic abdominal discomfort Dyspepsia Low grade fever Obstructive jaundice : Daughter cysts pass through cytobiliary communication Biliary rupture- jaundice, urticaria , biliary colic Nausea Vomiting Cough Hydatid emesia Hydatid enterica

22. Lungs: chronic cough dyspnea pleuritic chest pain hemoptysis . Cerebral involvement: headache dizziness decreased level of consciousness neurologic deficits

23. Presentations in emergency severe abdominal pain following minor trauma (CT scan may be diagnostic). Allergic reactions skin rash anaphylactic shock if cyst ruptures spontaneously, from trauma or surgery.

24. Examination Skin Jaundice urticaria and erythema spider angio mas -portal hypertension secondary to either biliary cirrhosis or obstruction of the inferior vena cava. Vital signs Fever -secondary infection or allergic reaction. Hypotension -with anaphylaxis secondary to a cyst leak Abdomen Abdominal tenderness. Hepatomegaly or mass Ascites is rare. Splenomegaly - splenic echinococcosis or portal hypertension.

25. Hydatid thrill Camellotte sign Lungs: Decreased breath sounds over the affected area -airway obstruction with consolidation Extremities Bone -tenderness, palpable mass. Muscle - palpable mass.

26. Differential diagnosis simple (bile duct) cyst benign adenoma focal nodular hyperplasia metastatic lesion biliary cystadenoma or cystadenocarcinoma primary hepatoma pyogenic or amoebic abscess

27. Investigations There should be a high index of suspicion. 1.Routine hematology – Elevated total leucocyte count eosinophilia . 2. Casoni’s intradermal test – Low sensitivity(75%) and specificity risk of anaphylactic reaction considered obsolete now.

28. Indirect haemagglutination test (IHA) L atex agglutination test (LT ) Immunoelectrophoresis (IEP ) Double diffusion test (DD) Enzyme linked immunosorbent assay ( ELISA) Radioallergosorbent test (RAST ) Complement fixation test (CFT) Bentonite flocculation test (BFT) Indirect fluorescent antibody test(IFAT) Counterimmune electrophoresis (CIE) Basophil degranulation test (BDT) 3. Immunological serology- primary tests

29. Initial screening -highly sensitive test like IHA or LT Confirmation - highly specific test like IEP, DD test, ELISA or RAST. Positive IEP test is highly specific for active infection (cross-reaction with Taenia solium cysticercosis only). ELISA and RAST are simple to perform and useful for population surveys. The only serological test that has a role in monitoring progress after surgical treatment of hydatids is CFT because it reverts to negative within 12 months of cure.

30. 4. Secondary laboratory tests Immunoblotting Polymerase chain reaction Detection of precipitation line- arc 5 More specific Useful in extra hepatic hydatid disease Calcified non-fertile liver hydatid

31. Imaging studies 5. Plain X-ray abdomen, chest: an elevated right hemdiaphragm . Calcification

32. 6. Ultrasonography (USG) easy availability, affordability and diagnostic sensitivity Reveals rosettes of daughter cysts Double contoured membrane of cyst due to detachment of cyst membranes calcification of cyst wall Role: Screening in endemic areas and in family members. First line diagnostics. Interventional non-operative procedures. Monitoring treatment and during follow-up. IOUS (Intra-operative ultrasound): useful for localization and management of small, nonpalpable or deep-seated cysts.

33. CLASSIFICATION OF HYDATID CYSTS based on ultrasonographic findings. Gharbi Classification of Hydatid Cysts Type I - pure fluid collection - univesicular cyst Type II - fluid collection with a split wall - detached laminated membrane - ‘water lily’ sign Type III - fluid collection with septa - daughter cysts Type IV - heterogenous appearance - presence of matrix - mimics a solid mass Type V - reflecting thick walls - calcifications Gharbi Classification of Hydatid Cysts Type I Pure fluid collection Type II Fluid collection with a split wall Type III Fluid collection with septa Type IV Heterogenous appearance Type V Reflecting thick walls

34. Classification In 2003, the WHO Informal Working Group on Echinococcosis (WHO-IWGE) proposed a standardized ultrasound classification based on the status of activity of the cyst. Universally accepted Helps to decide on the appropriate management. Group 1: Active group – cysts larger than 2 cm and often fertile . Group 2: Transition group – cysts starting to degenerate and entering a transitional stage because of host resistance or treatment, but may contain viable protoscolices . Group 3: Inactive group – degenerated, partially or totally calcified cysts; unlikely to contain viable protoscolices .

35. WHO classification Active unilocular no cyst wall early stage not fertile CL

36. CE1 Active Unilocular , simple cyst with uniform anechoic content. May exhibit fine echoes due to shifting of brood capsules i.e. hydatid sand (“ snow flake sign ”). fertile

37. CE2 Active Multivesicular , multiseptated cysts Cyst septations produce “wheel-like” structures Daughter cysts indicated by rosette-like or honeycomb-like structures. Daughter cysts may partly or completely fill the unilocular mother cyst.

38. CE3 Transitional Unilocular cyst which may contain daughter cysts. Anechoic content with detachment of laminated membrane from the cyst wall floating membrane or “water-lily sign” -wavy membranes floating on top of remaining cyst fluid.

39. CE4 Inactive Heterogenous hypoechoic or hyperechoic degenerative contents . No daughter cysts. Ball of wool sign - degenerating membranes.

40. CE5 Inactive Thick calcified wall that is arch shaped, producing a cone shaped shadow. Not fertile

41. 7. Computerised tomography (CT): best imaging modality maximum information of the position and extent of intra-abdominal hydatid disease volume of cyst can be estimated More accurate to identify cyst characteristics -cart wheel like- multivesicular rosette like. Diagnostic feature is a space-occupying lesion with a smooth outline with septa.

42. Computerised tomographic (CT) scan showing a hydatid cyst with septa in the left lobe of the liver.

43. Typical unilocular hydatid cyst. Unenhanced CT scan shows a large hydatid cyst with a noncalcified , high-attenuation wall in the right hepatic lobe (arrows).

44. Computerised tomographic (CT) scan of the upper abdomen showing a hypodense lesion of the left lobe of the liver; the periphery of the lesion shows a double edge. This is the lamellar membrane of the hydatid cyst that separated after trivial injury

45. 8. Magnetic resonance imaging (MRI) / MRCP: When there is jaundice to visualise biliary tree and its relation to hydatid cyst Cystobiliary communication Biliary hydatids in bile duct and hepatic ducts Much costlier . For non-invasive visualization of the pancreato-biliary complex.

46. Magnetic resonance cholangiopancreatography (MRCP) showing a large hepatic hydatid cyst with daughter cysts communicating with the common bile duct causing obstruction and dilatation of the entire biliary tree

47. 9. Endoscopic retrograde cholangiography (ERCP) Diagnostic and therapeutic role- with sphincterotomy in cases of biliary rupture of hydatid cyst. To find biliary communications. Can be used to drain biliary tree before surgery 10. Liver function tests : ALT , AST, GGT, ALP may be raised 11.Angiography lack of specificity invasive differential diagnosis of suspected malignancy or vascular malformation. 12. Radionuclide scan : most accurate demonstration of bronchobiliary fistula.   13. Immunoscintigraphy : radiolabelled antibodies to parasite.  

48. Complications Rupture Internal- into the cyst External- cyst bursts into surrounding structures Minor leaks : increased pain , mild allergic reaction characterized by flushing and urticaria . Major rupture : full-blown anaphylactic reaction, peritonitis Into the biliary tree : cholangitis , obstructive jaundice, or pancreatitis. Into the bronchi :expectoration of cyst fluid, scolices .

49. Infection liver abscesses Mild fever to full blown sepsis Allergic reactions Urticaria Brochospasm Anaphylaxis Eosinophilia Pressure Effects Obstructive Jaundice Budd- Chiari Syndrome Organ dysfunction Cholangitis Biliary Cirrhosis Spread, recurrence (8.5-25%) Spontaneous Rupture of Cyst Iatrogenic Puncture, Surgical Inoculation

50. Treatment No need of treatment in asymptomatic and inactive cysts– monitor size by ultrasound. Whether treated medically or in combination with surgery depends on → Number of cysts, size , anatomical position . co-morbid conditions Medical treatment Indications : Single uncomplicated cyst, < 4 cm Surgically unfit patients Recurrent cysts Widely disseminated hydatid disease. Localized disease with poor surgical risk. Ruptured cysts. Significant intraoperative spillage

51. Mebendazole : 40-50 mg /kg/day , plasma ≥74 ng /ml. Albendazole : 10-15 mg/kg/day (400 mg BD for 4 weeks, cycle repeated 3 times separated by 2 weeks intervals) Site : colchicine -sensitive site of tubulin → inhibits polymerization → impaired uptake of glucose Both active against germinal membrane Praziquantel : 40 mg/kg/day in 2 divided doses. Once a week as adjunct to albendazole More active against protoscoleces . .

52. Disease reassessed and decision taken either for surgery or continue chemotherapy( 1-year course ). Post-operatively : 2 weeks praziquantel + albendazole for material possibly spilled

53. Surgery Cystotomy , deroofing and omentoplasty Partial cystectomy Partial resection Marsupialisation and tube drainage or omentoplasty Radical surgical resection(total cystopericystectomy ) Partial hepatectomy , hepatic segmentectomy Minimal invasive Open surgery PAIR Laparoscopic cystotomy , deroofing and omentoplasty Children- deroofing + tube drainage, capitonnage , omentoplasty and pericystectomy

54. Principles of hydatid surgery 1) Total removal of all infective components of the cysts 2) avoidance of spillage of cyst contents at time of surgery 3) management of communication between cyst and adjacent structures 4) management of the residual cavity 5) minimize risks of operation

55. Scolicidal agents used during surgery Silver nitrate 0.5% Hypertonic saline (15–20%) Ethanol (75–95%) Povidone iodine 10% Chlorhexidine 0.5% Hydrogen peroxide 3% Formaldehyde not used They may cause sclerosing cholangitis if biliary radicles are in communication with the cyst wall.

56. PAIR: percutaneous therapy by puncture, aspiration, injection and reaspiration Relatively recent and minimally invasive therapeutic option, that complements or replaces surgery For uncomplicated liver cysts Done after adequate drug treatment with albendazole ( praziquantel )- pre-operative: 3 months

57. Indications for PAIR Patients with: • Non-echoic lesion ≥ 5 cm in diameter • Cysts with daughter cysts (CE2), and/or with detachment of membranes (CE3) • Multiple cysts if accessible to puncture • Infected cysts • Pregnant women • Children >3 years old • Patients who fail to respond to chemotherapy alone • Patients in whom surgery is contraindicated • Patient who refuse surgery • Patients who relapse after surgery

58. Contraindications to PAIR Non-cooperative patients and inaccessible or risky location of the cyst in the liver Cyst in spine, brain and/or heart Inactive or calcified lesion Cysts communicating with the biliary tree Cysts open into the abdominal cavity, bronchi and urinary tract

59. Done under US/CT guidance Under local anaesthesia cyst is punctured using a cholangiography 22 gauge needle through thickest part of wall Parasitological examination (if possible) or fast test for antigen detection in cyst fluid is carried out. 10-15 cc of cystic fluid is aspirated . Cyst fluid is tested for bilirubin . If bilirubin is present: stop the procedure. If no bilirubin is present: aspirate all cystic fluid. 95% ethanol solution or hypertonic saline 15-20% (1/3 of the amount of aspirated fluid) is injected . Reaspiration of protoscolicide solution after 5 minutes. Technique

60. Benefits of PAIR Minimal invasiveness Reduced risk compared with surgery Confirmation of diagnosis Removal of large numbers of protoscolices with the aspirated cyst fluid Improved efficacy of chemotherapy given before and after puncture Reduced hospitalization time Cost of the puncture and chemotherapy usually less than that of surgery or chemotherapy alone

61. Complications of PAIR Urticaria Anaphylaxis Subcapsular haematoma Fever Biliary fistula Secondary infection of cyst cavity Hypotension/ hypotensive shock

62. Surgery Preoperative steroids may be used. Incisions- midline or right subcostal Abdomen is completely explored, liver mobilised and cyst exposed Peritoneal cavity is packed with coloured mops (To identify pearly white scolices , prevent spillage) Cyst is aspirated through a closed-suction system Scolicidal agents are injected into cyst cavity Hypertonic saline should be left within cavity for 15-20 minutes to have effect, others- 5 min Cyst is unroofed

63. After entering in the abdominal cavity with middle incision, the large right lobe hydatid cyst is identified .

64. The hydatid cyst is unroofed and evacuated by aspiration. Remaining daughter cysts are removed after repetitive infusions of hypertonic saline solutions and chlorexidine

65. Conservative technique Evacuation of the cyst contents and leaving the pericyst . The residual pericyst is managed by: marsupialization , which consists of suturing the edges of opened pericyst with the skin capitonnage - spiral suturing of the bottom of cavity upward from base of cavity to edge of cyst wall partial pericystectomy omentoplasty ( omentum is thought of fill residual cavity, to assist healing of raw surfaces and to promoted resorption of serosal fluid and macrophagic migration of septic focus) suture closure of the pericyst cavity after filling it with saline. 

66. Placement of the sutures in the lateral anterior edge of the cystic wall remnant. Then the interior edge is sutured and anchored in the posterior wall.

67. The capitonnage is completed when the edges of the anterior cystic wall remnants are sutured in the posterior wall. The capitonage prevents the postoperative "dead" space, which facilitates the fluid collection.

68. In the previous cavity of the cyst, under the capitonage , drainage is placed. The penrose drainage will be removed the 2 nd postoperative day.

69. Open cyst evacuation-aspiration, removal of daughter cysts, resection of active cyst lining, packing with omentum ,

70. Indications for external drainage Infected cyst Biliary communication not found Hemorrhagic cyst Primary closure not possible Omentoplasty not possible

71. Radical surgical procedures Cystectomy Pericystectomy Hepatic resections: Segmental hemihepatectomy Complications Biliary leakage Risk factors: purulent and/or bilious contents, Male, preoperative  alkaline phosphatase and gamma- glutamyl transferase Biliary fistula Infection of residual cavity Cholangitis

72. AARONS HYDATID CONE To reduce spillage and consequent secondary implantation Cryogenic cone (1971)- adhered by freezing damaged tissues and structures, and an unreliable seal . In 1983 Barrie Aarons , surgeon at Hamilton (Vic.) Australia, perfected a cone which adhered to the surface of the liver by suction . Set of 2 cones: first having conical part vertically above suction base, other with conical part tilted to 20◦ to vertical

73. Area of cyst wall >cone base is exposed, Cone of best fit is placed in position → suction applied to obtain seal. Hydatid fluid wells into the cone →removed by a separate wide-bore sucker. Cyst cavity is then aspirated, hydatid membrane is removed Cavity is sterilized and closed.