Hydatid Disease of the Lungs Study of 386 Cases1.2
MOHAMED JERRAY, MOHAMED BENZARTI, ABDELHAMID GARROUCHE, NEJI KLABI, and ABDELAZIZ HAYOUNI
Introduction
Hydatid disease is a parasitic infection caused by several species of the cestode Echinococcus. The most common form is E. granulosus, which gives rise to cysts primarily in the liver and the lungs. The adult worm E. granulosus lives in the intestine of dogs and other canine species (definitive hosts) attached to the mucosa by hooklets (1); its terminal segment contains hundreds of eggsthat are passed in the stool. Eggs ingested by cows,sheep, or humans (intermediate hosts) liberate an embryo in the duodenum, which rapidly passes through the intestinal wall to enter the portal bloodstream (1,2). Embryos are carried to the liver, where most are arrested in hepatic capillaries. Some pass through the liver to the capillary sieve of the lung and to other organs. More than 85070 are filtered by the liver and lungs, where they lodge and develop into hydatid cysts. The life cycle is completed when an infectedintermediate host dies and its viscera, which contain the larval form, are consumed by a definitive host (2). The hydatid cyst has three layers (1). The outer pericyst is dense and fibrous because of host reaction; the middle laminated membrane is acellular and permits the passage of nutrients; the inner, germinal or germinative layer produces the scolices that represent the larval stage. The cyst fluid is crystal clear. It is a transudate of serum, contains proteins, and is antigenic. If released into the host's bloodstream, it can cause eosinophilia and anaphylaxis (1). Hydatid disease is endemic to many parts of the world, including South America, Australia, and the Middle East and Mediterranean areas. The liver and lungs are the organs most frequently involved (75% liver, 15% lungs, and 10% the rest of the body) (1). The present report describes our experience with 386 patients with lung cysts studied at one hospital during a 1O-yr period.
SUMMARY During a 10-yr period, 386 patients with hydatid disease of the lung were treated at our hospital. There were 165 male and 221 female patients with a mean age of 30.15 + 16.9 yr. There were 286 solitary, 20 multiple, and 21 bilateral cysts. In 59 patients, the cysts Included the lung and other organs; in 54, the lung and the liver; In four, the lung and the kidney; in one, the lung and the peritoneum. Diagnosis was made using clinical criteria, serologic findings, and ImagIng techniques; 373 patients were treated surgically. Surgical procedures consisted of cystectomy in 93 patients, pericystectomy In 166 patients, and lung resection in 114patients. Mebendazole and flubendazole were used In three patients. Postoperative complications occurred in 44 patients (15.8%). There were two operative deaths (mortality rate, 0.53%). Patients have been followed yearly, with a median follow-up of 6 yr. Active hydatid disease has been found In two patients. AM REV RESPIR DIS 1992; 146:185-189
Methods Between 1980and 1990, 386 patients with pulmonary cysts caused by E. granulosus were admitted to the Pulmonary Center of the Sousse University Hospital. Hydatid disease was confirmed by pathologic examination of removed tissue in resected patients, and in the remaining patients it was diagnosed by clinical, serologic, and radiologic findings. Data compiled for each patient included demographic information (sex, age, occupation). Laboratory tests included cell blood count with eosinophil count and serology. Eosinophilia is defined as more than 500 eosinophils per cubic millimeter. Echinococcal indirect hemagglutination titers greater than 1:320 were considered to be significant. The presence of the arc 5 in immunoelectrophoresis was considered diagnostic. Plain chest and abdominal radiographs were performed in all cases. Computerized tomographic (CT) scanning, available only recently, was used in only five patients. Preoperative investigations included a full pulmonary function test, a complete blood count with white blood cell differential and platelet counts, tests for serum electrolyte calcium, liver function tests including serum glutamic-oxaloacetic transaminase, alkaline phosphatase, and bilirubin, and renal function tests including blood urea nitrogen and creatinine. Bronchoscopy was performed prior to surgery in 106 patients. To exclude liver cysts, ultrasound was performed in all cases. Preoperative diagnosis of hydatid cyst of the lung was corroborated or established by serologic tests in 270 patients, by the pathognomonic "double arch" and "water-lily" sign
of a ruptured hydatid cyst on chest radiographic examination in 55 patients, by fiberoptic bronchoscopy showing typical endobronchial white and gelatinous membranes in 21 patients, and by presumptive diagnosis in 42 patients. A presumptive diagnosis of pulmonary hydatid cyst was based on the following criteria: (1) patient from an endemic area, (2) history of sudden cough and expectoration of cyst fluid and membranes, (3) chest radiograph consistent with hydatid cyst (welldefined and round cyst, thick-walled cavity with an air fluid level), (4) no other causes of lung disease found. There were 373 patients who were treated surgically (five refused surgery, and five more were medically unfit for surgery). Three patients with severe pulmonary and hepatic hydatid disease were treated medically with mebendazole and flubendazole. After treatment patients were discharged from the pulmonary center and seen for evaluation according to the following schedule: 3, 6, and 12 months and then at yearly intervals at which clinical history, physical examination, and routine radiography ofthe chest and abdomen were performed. Follow-up ranged from 1 to 10 yr.
(Received in original form June 25, 1991 and in revised form March 12, 1992) 1 From the Pulmonary Disease Department, University Hospital, Sousse, Tunisia. 2 Correspondence and requests for reprints should be addressed to Dr. M. J erray, Department of Pulmonary Disease, University Hospital, 4000 Sousse, Thnisia.
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TABLE 1
TABLE 3
AGE AND SEX DISTRIBUTION OF THE PATIENTS
RADIOLOGIC FINDINGS Characteristics
(n)
(%)
Well-defined round cyst Appearances of lung abcess Water-lily sign Crescent sign Pleural effusion Translucent cyst (bulla) Calcification Hydropneumothorax
201 78 55 43 13 6 3 1
52.2 20.3 14.2 11.2 3.4 1.3 0.7 0.2
Patients Male
Female
Total
(%)
9 62 40 20 12 11 10 1
6 55 58 29 34 16 21 2
15 117 98 49 46 27 31 3
3.9 30.3 25.4 12.7 12.0 7.0 8.0 0.7
165
221
386
Age. yr
5-10 11-20 21-30 31-40 41-50 51-60 61-70 > 70 Total
100
TABLE 2 PROMINENT SYMPTOMS IN 386 PATIENTS Presenting Sign or Symptom
(n)
(%)
Cough Hemoptysis Chest pain Expectoration of cyst fluid and membranes Fever and purulent sputum Dyspnea Rash. prurltis, or urticaria Asymptomatic
172 226 231 43 78 53 10 11 8
52.2 68.7 69.8 11.2 19.8 13.8 2.8 3.0 2.3
Results
Of the 386 patients, 165were male (mean age, 27.6 + 16.32 yr) and 221 were female (mean age, 32.7 + 17.8 yr). The mean age of all patients was 30.15 + 16.93 yr (mean + SD). More than half (55.7070) were between 10 and 30 yr of age (table 1). Of the 20070 of patients for whom occupational data were available, 34070 were agricultural workers and 0.5070 were shepherds; the remaining pursued a variety of indoor occupations; 42070 were from rural areas, and 53.2070 owned dogs. Fifteen household members of patients with hydatidosis had previously been operated on for hydatid cyst (nine pulmonary cysts, six liver cysts). Of our patients, 25 had had previous surgery for hydatid disease before being referred to our center (14 pulmonary cysts, 10 liver cysts, and one brain cyst). Clinical presentation is shown in table 2. Cough, hemoptysis, and chest pain were the most common symptoms. In 19.8070 of the patients there was sudden cough and expectoration of cyst fluid, membranes, and scolices, and fever and purulent sputum in 119 patients (31070). Twelve patients (3070) had symptoms or history of allergic episodes. Three patients (0.7070) were admitted with pleural effusion and one with hydropneumothorax; 2.3070 of the patients denied having
TABLE 4 SITES OF HYDATID CYSTS IN 386 PATIENTS Sites
(n)
(%)
Pulmonary Solitary Right upper Left upper Left lower Right lower Right middle Multiple in one lung Bilateral
327 286 37 34 67 71 26 20 21
84.7 74.0 9.5 8.8 17.3 18.4 6.7 5.1 6.7
54 4 1
13.9 1.0 0.2
Pulmonary + hepatic Pulmonary + renal Pulmonary + peritoneal
any symptoms and presented after routine chest radiography. Eosinophilia was noted in 24.8070 of the patients. In the serologic tests, 75070 of the immunoelectrophoresis was positive; in the latex hemagglutination test, 54.1% was positive.
Radiologic Findings All patients had abnormal chest radiographs (table 3). The most common abnormal findings on plain radiography were well-defined, round cysts (52.2070). In 20.3070 the appearances were those of lung abscess, with a thick-walled cavity and an air-fluid level surrounding pneumonia. Perivesicular pneumocysts or crescent signs were seen in 11.2070; the iceberg or water-lily sign in 14.2070; a translucent cyst resembling a bulla in 1.3070; pleural effusion in 3.4070; hydropneumothorax in 0.2070; calcification of the cyst wall in 0.7070 (two patients). Liver ultrasound revealed hepatic cysts in 54 patients (15%).
There was a predilection for the right lung (56.8070) and for the lower lobes (59070). In 21 patients bronchoscopy revealed the presence of white, gelatinous, and transparent material composed of laminated membranes. In these latter cases the presence of echinococcus was confirmed by identification of the hydatid elements.
Treatment There were 373 patients who were treated surgically. The approach was thoracic in 350 and combined (abdominal and thoracic) in 23 for simultaneous pulmonary and hepatic echinococcosis. Meticulous care was taken in removing fluid and cysts contents; hypertonic saline (3070) was instilled within cysts before the evacuation of their contents; pleural space was protected by packing and irrigation with hypertonic saline. The surgical procedure (table 5) included cyst evacuation (enucleation) for 93 patients (24.6070), complete cyst resection in 69 patients (18.3070), partial cyst resection in 97 patients (25.7070), segmentectomy in 64 patients (16.9070), lobectomy in 48 patients (12.6070), and bilobectomy and pneumonectomy in one patient each (0.26070). Postoperative Complications These occurred in 44 patients (11.8070) and included prolonged air leaks in nine patients, atelectasis necessitating bronchoscopy in two patients, aspiration pneumonia in 11 patients, and empyema in four patients (table 5). There were two operative deaths (mortality rate, 0.53070); cause of death was cardiac arrest in one and respiratory failure in the other. During the follow-up period, active hydatid lung disease was found in only two patients (0.53070). They underwent a second pulmonary resection. One had lobectomy and one had segmentectomy; there were no postoperative complications and no operative deaths. The free interval between the first pulmonary resection and the discovery of the sec-
TABLE 5 POSTOPERATIVE COMPLICATIONS
Sites of Involvement There were 327 patients who had disease localized to the lung (table 4). Of these, 59 (15070) had extrapulmonary cysts of which 54 were hepatic, four renal, and one intraperitoneal. Lung cysts were unique in 286 cases (74.4%), multiple in 20 (5.1070), and bilateral in 21 (5.8070).
Complications
(n)
(%)
Wound infection Pneumonia Prolonged air leak Empyema Atelectasis Hydropneumothorax Total
17 11 9
38.6 25 20.4 9 4.5 2.2 100
4 2 1
44
187
HYDATID DISEASE OF THE WNGS
ond lung cyst was 27 and 39 months, respectively; the cyst was single, and the location was in the ipsilateral lobe in both cases. At the time of this report 420/0 of patients were living free of disease and had been followed for 12to 120months after discharge; 12% were lost to follow-up within 12months, 17% within 24 months, and 27% within 36 months. Nine (2%) patients died of other causes. Discussion
Hydatid disease is a widespread problem throughout the world, and the only effective treatment is surgical excision. It is prevalent in Tunisia, especially in central Tunisia. In this region echinococcosis caused by E. granulosus represents a zoonosis of major public health importance. The liver and lungs are most frequently involved (75% liver, 15% lung, and 10% the rest of the body) (1). In our area, lungs were involved in 35% (3). There may be geographic differences in organ distribution related to some biologic factors in parasite or host. Most cysts are acquired in childhood and are not diagnosed until the third or fourth decade (1,4,5). Cysts grow faster in compressible organs such as the lung, and this may account for the relatively high incidence of the disease in this organ in childhood (5). In children some series indicate that pulmonary involvement is more frequent than hepatic involvement (6). In our study more than one-third of patients werebetween 5 and 20 yr of age, and 58% were between 5 and 30 yr of age. Hydatidosis was more frequent in female than in male patients. The male-to-female ratio in our serieswas 0.74;higher incidence rates were observed in female patients in all age groups except for the 5- to 20-yr range. This predominance of hydatidosis in women is found in most reports from northern Africa (7, 8); this might to be due to sex-related behavioral differences with respect to direct and indirect exposure to dogs and dog feces. The cycle of E. granulosus is considered to be essentially rural, involving predominantly the sheep as the intermediate host and the dog as the definitive host (9). In our series only 42% of the patients were from rural areas; these results suggest strongly that in addition to the rural cyclethere is an urban cycle (10). The diagnosis of hydatid lung disease can frequently be suspected on clinical findings that are compatible with the disease in those who have had contact with an appropriate host.
Imaging techniques such as radiography, ultrasound, and nuclear scanning have enabled accurate localization and definition of lung lesion. Furthermore, serologic tests based on the host immune response to the Echinococcus organism have provided additional diagnostic tools. In our experience the most common clinical presentations were cough, hemoptysis, and chest pain. Allergic reactions are not as common as was once thought, although fatal anaphylaxis does occur (11). Twelvepatients (3%) had histories of allergic episodes after cyst rupture, but none had fatal anaphylaxis. The most serious usual complication of rupture is bacterial infection; 119 patients (31%) had symptoms of bacterial infection. Both rupture and infection can change the appearance of hydatid cyst. Although many of the presenting features are similar, the point of differentiation is the incidence of fever; patients with hydatid cyst are rarely febrile (12). Radiographs ofthe chest allow recognition of pulmonary cysts (13). Intact cysts are usually well demarcated (figure 1), although cysts have several different appearances. As the cyst enlarges, it erodes bronchioles, and air is introduced betweenthe pericyst and laminated membrane and appears as a thin, lucent crescent in the upper part of the cyst, producing the crescent or meniscus sign (figure
Fig. 1. Radiograph of the chest showing two well-defined cysts in the left lung.
2). In older and infected cysts, a thick cyst wall caused by adjacent atelectasis and reactive change can be seen on the radiograph, with the classic double-arch, or water-lily(figure 3) sign within hydatid cysts (14). Other imaging techniques, therefore, are needed to detect and evaluate possible extrathoracic hydatid cysts. Ultrasound is very sensitive in revealing cysts and in identifying certain characteristic features of hydatid disease (15). Currently, the most effective imaging technique available to us is the CT scan; it is highly sensitive, and it can discover additional small intrathoracic lesions. In addition, it plays a major role in the preoperative assessment of the disease (16, 17). Curvilinear or ringlike calcification, which can develop on the rim of the cyst, is more common in older cysts and in hepatic cysts. Of 58 patients who had hepatic cysts, calcification was visible on plain films in about 45%. These calcified cysts of the liver with negative clinical laboratory tests need no specific treatment. Calcification develops in thoracic cysts much less commonly (13, 17), 0.7% in our series. Blood eosinophilia is usually minimal or absent, but it may increase with episodes of cyst leakage. It occurs in about 40% of patients (18). Serologic testing is the method of choice to corroborate the diagnosis (19).
188
JERRAY, BENZARTI, GARROUCHE, KLABI, AND HAYOUNI
Fig. 2. Chest radiograph showing the typical meniscus sign. Air outlines the pericyst (arrows).
There are now many sensitive and specific serologic tests available such as indirect hemagglutination, indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and latex fixation. Although these assays are sensitive, false-positive reactions can occur, most commonly in patients with other helminthic infections. Negative serologic tests do not exclude the diagnosis of echinococcosis (20). Of the serologic tests, immunoelectrophoresis has been found to be the most sensitive (75070 posi-
tivity compared with 54.1% for indirect hemagglutination). False-negative results occur mostly with unruptured cysts, especially in children (2). Surgery is the treatment of choice. A variety of approaches have been described. Cystectomy consists of removal of the endocyst only and leaves behind the pericyst; the parasite is enucleated intact by gentle dissection (21).Partial and total pericystectomy eradicates the parasite without damaging healthy parenchyma, and it leaves a clear-cut section be-
Fig. 3. Large ruptured cyst in left lung (arrow); the parasite lies collapsed (arrowhead) within it showing the pathognomonic "water-lily" sign of ruptured hydatid cyst.
hind; the residual pericyst may be left open or obliterated by capitonnage, which consists of stitching the remaining lung cavity (22). Segmentectomy, lobectomy and pneumonectomy may also be carried out when lung tissue is diffusely involved. In the group of patients with ruptured and infected cysts, 87% were treated by lung resection, and postoperative complications were more common (39 of 44 complications occurred in the latter group). In the group of patients with intact cysts, only five complications were seen. The difference in complication rates between these two groups is statistically significant. Mean hospital stays for these groups were, respectively, 27 and 11 days (p < 0.0001). Medical therapy of hydatid disease is difficult to evaluate, although high-dose mebendazole has been reported to be effective in some patients (23-25). In our experience three women unfit for surgery were treated medically, one with mebendazole and two with flubendazole. They were placed on several courses of drugs, 6 g/day. One 54-yr-old patient was treated with mebendazole for 4 yr. In this patient the response to therapy was slow, with mild clinical improvement. She was last seen in September 1990. She continues to have expectoration of cyst fluid, membranes, and scolices; a chest radiograph showed multiple-ruptured cysts in both lungs. The two latter patients (26 and 34 yr of age, respectively) received flubendazole 6 g/day; they were lost to follow-up after only 3 months of observation. The present study indicates that the hydatid recurrence rate is 0.5%. Unfortunately, there is remarkably little data in the literature on recurrence rates for lung hydatids. Chevret and coworkers (26) have reported a recurrence rate of 2.9% in 1,397 patients. On the basis of our experience, the following conclusions can be made. (1) Lung hydatidosis is predominantly a disease of the young and of the middle-aged adult. (2) This disease should be suspected in patients from endemic areas. (3) The diagnosis of a hydatid cyst of the lung is an indication for the examination of the liver because multiple echinococcal cysts are common and ultrasound has a high accuracy in the diagnosis of the lesion. (4) Immunoelectrophoresis is the most sensitive diagnostic test. (5) To date no effective medical treatment is available, and surgery remains the best hope for cure. (6) A health education program adapted to the specific sociocultural tra-
189
HYDATID DISEASE OF THE WNGS
ditions is needed to promote preventive measures. References 1. Saidi E Surgery of hydatid disease. Philadelphia: W. B. Saunders, 1976. 2. Radford AJ. Hydatid disease. In: Weatherall DJ, Ledingham JGG, Warrel DA, eds. Oxford textbook of medicine. Oxford: Oxford University Press, 1982; 5442-4. 3. Kehila M, Ammar N, Hattab Ch, et al. Etude statistique de localisations hydatiques. Tunis Med 1988; 66:587-91. 4. Carcassone M, Aubrespy P, Dor V, Choux M. Hydatid cysts in childhood. Prog Pediatr Surg 1973; 5:1-35. 5. Bloomfield JA. Hydatid disease in children and adolescents. Australas Radiol 1980; 24:277-83. 6. Matsaniotis N, Karpathios T, Koutoyzis J, et al. Hydatid in Greek children. Am J Trop Med Hyg 1983; 32:1075-8. 7. Benhailes N, Ouchfoun A, Chkarine V. Evaluation d'une annee de mise sous surveillance epidemiologique de I'hydatidose. Bull Epidemiol INSP (Alger) 1981; 1-22. 8. Laouar M. Aspects epidemiologiques actuels de l'hydatidose humaine dans l'est algerien. These pour Ie doctorat en sciences medicales, Alger 1987.
9. Euzeby J. Les echinococcoses animales et leurs relations avec les echinococcoses de I'homme. Paris; Vigot, 1971. 10. Bchir A, Jaiem A, Jemmali M, Rousset 11, Gaudebout C, Larouze B. Possible existence of an urban cycle of Echinococcusgranulosisin central Tunisia. Trans R Soc Trop Med Hyg 1987; 81:650. 11. Beggs I. The radiologic appearances of hydatid disease of the liver. Clin Radiol 1983; 34:555-63. 12. Altemeier WA, Schowengerds CG, Whiteley DH. Abscesses of the liver: surgical considerations. Arch Surg 1970; 101:258-66. 13. Beggs I. The radiology of hydatid disease. AJR 1985; 145:639-48. 14. Ramos L, Hernandez-Mora M, IIIana M, Liorente MT, Marcos J. Radiological characteristics of perforated pulmonary hydatid cysts. Radiology 1975; 116:539-42. 15. David B, Lewall MD, Scott J, McCorkell MD. Hepatic echinococcal cysts: sonographic appearance and classification. Radiology 1985; 155:773-7. 16. Diego Choliz J, Lecumberri Olaverrif J, Franquet Casas Ostiz Zubeita S. Computed tumography in hepatic echinococcosis. AJR 1982; 139: 699-702. 17. Saksouk FA, Fahl MH, Rizk GK. Computed tomography of pulmonary hydatid disease. J Comput Assist Tomogr 1986; 10:226-32. 18. Balikian JP, Mudarris FE Hydatid disease of
the lungs: a roentgenologic study of 50 cases. AJR 1974; 122:692-707. 19. Schantz PM, Kagan IG. Echinococcosis (hydatidosis). In: Houba V, ed. Immunologic investigation of tropical parasitic disease. New York: Churchill Livingstone, 1980; 104-29. 20. Scully RE, Mark EJ, McNeely WF, McNeely BU. Case records of the Massachusetts General Hospital. N Engl J Med 1987; 317:209-18. 21. Slim MS, Khayat G, Nasr MT, Judejian YD. Hydatid disease in childhood. J Pediatr Surg 1971; 6:440-8. 22. Sarsam A. Surgery of pulmonary hydatid cysts. J Thorac Cardiovasc Surg 1971; 62:663-8. 23. Bekhti A, Schaaps JP, Capron M, et al. Treatment of hepatic hydatid disease with mebendazole: preliminary results in four cases. Br Med J 1977; 2:1047-50. 24. Beard CT, Rickard MD, Goodman HT. Medical treatment for hydatids. Med J Aust 1978; 1:633-5. 25. Bryceson ADM, Cowie AGA, Mcleod C, et al. Experience with the treatment of inoperable hydatid disease in England. Trans R Soc Trop Med Hyg 1982; 76:510-8. 26. Chevret R, J ouharia A, Rahali R. Kysteshydatiques du poumon. Le problerne des recidives. Chirurgie 1980; 106:673-82.
MOHAMED JERRAY, MOHAMED BENZARTI, ABDELHAMID GARROUCHE, NEJI KLABI, and ABDELAZIZ HAYOUNI
Introduction
Hydatid disease is a parasitic infection caused by several species of the cestode Echinococcus. The most common form is E. granulosus, which gives rise to cysts primarily in the liver and the lungs. The adult worm E. granulosus lives in the intestine of dogs and other canine species (definitive hosts) attached to the mucosa by hooklets (1); its terminal segment contains hundreds of eggsthat are passed in the stool. Eggs ingested by cows,sheep, or humans (intermediate hosts) liberate an embryo in the duodenum, which rapidly passes through the intestinal wall to enter the portal bloodstream (1,2). Embryos are carried to the liver, where most are arrested in hepatic capillaries. Some pass through the liver to the capillary sieve of the lung and to other organs. More than 85070 are filtered by the liver and lungs, where they lodge and develop into hydatid cysts. The life cycle is completed when an infectedintermediate host dies and its viscera, which contain the larval form, are consumed by a definitive host (2). The hydatid cyst has three layers (1). The outer pericyst is dense and fibrous because of host reaction; the middle laminated membrane is acellular and permits the passage of nutrients; the inner, germinal or germinative layer produces the scolices that represent the larval stage. The cyst fluid is crystal clear. It is a transudate of serum, contains proteins, and is antigenic. If released into the host's bloodstream, it can cause eosinophilia and anaphylaxis (1). Hydatid disease is endemic to many parts of the world, including South America, Australia, and the Middle East and Mediterranean areas. The liver and lungs are the organs most frequently involved (75% liver, 15% lungs, and 10% the rest of the body) (1). The present report describes our experience with 386 patients with lung cysts studied at one hospital during a 1O-yr period.
SUMMARY During a 10-yr period, 386 patients with hydatid disease of the lung were treated at our hospital. There were 165 male and 221 female patients with a mean age of 30.15 + 16.9 yr. There were 286 solitary, 20 multiple, and 21 bilateral cysts. In 59 patients, the cysts Included the lung and other organs; in 54, the lung and the liver; In four, the lung and the kidney; in one, the lung and the peritoneum. Diagnosis was made using clinical criteria, serologic findings, and ImagIng techniques; 373 patients were treated surgically. Surgical procedures consisted of cystectomy in 93 patients, pericystectomy In 166 patients, and lung resection in 114patients. Mebendazole and flubendazole were used In three patients. Postoperative complications occurred in 44 patients (15.8%). There were two operative deaths (mortality rate, 0.53%). Patients have been followed yearly, with a median follow-up of 6 yr. Active hydatid disease has been found In two patients. AM REV RESPIR DIS 1992; 146:185-189
Methods Between 1980and 1990, 386 patients with pulmonary cysts caused by E. granulosus were admitted to the Pulmonary Center of the Sousse University Hospital. Hydatid disease was confirmed by pathologic examination of removed tissue in resected patients, and in the remaining patients it was diagnosed by clinical, serologic, and radiologic findings. Data compiled for each patient included demographic information (sex, age, occupation). Laboratory tests included cell blood count with eosinophil count and serology. Eosinophilia is defined as more than 500 eosinophils per cubic millimeter. Echinococcal indirect hemagglutination titers greater than 1:320 were considered to be significant. The presence of the arc 5 in immunoelectrophoresis was considered diagnostic. Plain chest and abdominal radiographs were performed in all cases. Computerized tomographic (CT) scanning, available only recently, was used in only five patients. Preoperative investigations included a full pulmonary function test, a complete blood count with white blood cell differential and platelet counts, tests for serum electrolyte calcium, liver function tests including serum glutamic-oxaloacetic transaminase, alkaline phosphatase, and bilirubin, and renal function tests including blood urea nitrogen and creatinine. Bronchoscopy was performed prior to surgery in 106 patients. To exclude liver cysts, ultrasound was performed in all cases. Preoperative diagnosis of hydatid cyst of the lung was corroborated or established by serologic tests in 270 patients, by the pathognomonic "double arch" and "water-lily" sign
of a ruptured hydatid cyst on chest radiographic examination in 55 patients, by fiberoptic bronchoscopy showing typical endobronchial white and gelatinous membranes in 21 patients, and by presumptive diagnosis in 42 patients. A presumptive diagnosis of pulmonary hydatid cyst was based on the following criteria: (1) patient from an endemic area, (2) history of sudden cough and expectoration of cyst fluid and membranes, (3) chest radiograph consistent with hydatid cyst (welldefined and round cyst, thick-walled cavity with an air fluid level), (4) no other causes of lung disease found. There were 373 patients who were treated surgically (five refused surgery, and five more were medically unfit for surgery). Three patients with severe pulmonary and hepatic hydatid disease were treated medically with mebendazole and flubendazole. After treatment patients were discharged from the pulmonary center and seen for evaluation according to the following schedule: 3, 6, and 12 months and then at yearly intervals at which clinical history, physical examination, and routine radiography ofthe chest and abdomen were performed. Follow-up ranged from 1 to 10 yr.
(Received in original form June 25, 1991 and in revised form March 12, 1992) 1 From the Pulmonary Disease Department, University Hospital, Sousse, Tunisia. 2 Correspondence and requests for reprints should be addressed to Dr. M. J erray, Department of Pulmonary Disease, University Hospital, 4000 Sousse, Thnisia.
185
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JERRAY, BENZARTI, GARROUCHE, KLABI, AND HAYOUNI
TABLE 1
TABLE 3
AGE AND SEX DISTRIBUTION OF THE PATIENTS
RADIOLOGIC FINDINGS Characteristics
(n)
(%)
Well-defined round cyst Appearances of lung abcess Water-lily sign Crescent sign Pleural effusion Translucent cyst (bulla) Calcification Hydropneumothorax
201 78 55 43 13 6 3 1
52.2 20.3 14.2 11.2 3.4 1.3 0.7 0.2
Patients Male
Female
Total
(%)
9 62 40 20 12 11 10 1
6 55 58 29 34 16 21 2
15 117 98 49 46 27 31 3
3.9 30.3 25.4 12.7 12.0 7.0 8.0 0.7
165
221
386
Age. yr
5-10 11-20 21-30 31-40 41-50 51-60 61-70 > 70 Total
100
TABLE 2 PROMINENT SYMPTOMS IN 386 PATIENTS Presenting Sign or Symptom
(n)
(%)
Cough Hemoptysis Chest pain Expectoration of cyst fluid and membranes Fever and purulent sputum Dyspnea Rash. prurltis, or urticaria Asymptomatic
172 226 231 43 78 53 10 11 8
52.2 68.7 69.8 11.2 19.8 13.8 2.8 3.0 2.3
Results
Of the 386 patients, 165were male (mean age, 27.6 + 16.32 yr) and 221 were female (mean age, 32.7 + 17.8 yr). The mean age of all patients was 30.15 + 16.93 yr (mean + SD). More than half (55.7070) were between 10 and 30 yr of age (table 1). Of the 20070 of patients for whom occupational data were available, 34070 were agricultural workers and 0.5070 were shepherds; the remaining pursued a variety of indoor occupations; 42070 were from rural areas, and 53.2070 owned dogs. Fifteen household members of patients with hydatidosis had previously been operated on for hydatid cyst (nine pulmonary cysts, six liver cysts). Of our patients, 25 had had previous surgery for hydatid disease before being referred to our center (14 pulmonary cysts, 10 liver cysts, and one brain cyst). Clinical presentation is shown in table 2. Cough, hemoptysis, and chest pain were the most common symptoms. In 19.8070 of the patients there was sudden cough and expectoration of cyst fluid, membranes, and scolices, and fever and purulent sputum in 119 patients (31070). Twelve patients (3070) had symptoms or history of allergic episodes. Three patients (0.7070) were admitted with pleural effusion and one with hydropneumothorax; 2.3070 of the patients denied having
TABLE 4 SITES OF HYDATID CYSTS IN 386 PATIENTS Sites
(n)
(%)
Pulmonary Solitary Right upper Left upper Left lower Right lower Right middle Multiple in one lung Bilateral
327 286 37 34 67 71 26 20 21
84.7 74.0 9.5 8.8 17.3 18.4 6.7 5.1 6.7
54 4 1
13.9 1.0 0.2
Pulmonary + hepatic Pulmonary + renal Pulmonary + peritoneal
any symptoms and presented after routine chest radiography. Eosinophilia was noted in 24.8070 of the patients. In the serologic tests, 75070 of the immunoelectrophoresis was positive; in the latex hemagglutination test, 54.1% was positive.
Radiologic Findings All patients had abnormal chest radiographs (table 3). The most common abnormal findings on plain radiography were well-defined, round cysts (52.2070). In 20.3070 the appearances were those of lung abscess, with a thick-walled cavity and an air-fluid level surrounding pneumonia. Perivesicular pneumocysts or crescent signs were seen in 11.2070; the iceberg or water-lily sign in 14.2070; a translucent cyst resembling a bulla in 1.3070; pleural effusion in 3.4070; hydropneumothorax in 0.2070; calcification of the cyst wall in 0.7070 (two patients). Liver ultrasound revealed hepatic cysts in 54 patients (15%).
There was a predilection for the right lung (56.8070) and for the lower lobes (59070). In 21 patients bronchoscopy revealed the presence of white, gelatinous, and transparent material composed of laminated membranes. In these latter cases the presence of echinococcus was confirmed by identification of the hydatid elements.
Treatment There were 373 patients who were treated surgically. The approach was thoracic in 350 and combined (abdominal and thoracic) in 23 for simultaneous pulmonary and hepatic echinococcosis. Meticulous care was taken in removing fluid and cysts contents; hypertonic saline (3070) was instilled within cysts before the evacuation of their contents; pleural space was protected by packing and irrigation with hypertonic saline. The surgical procedure (table 5) included cyst evacuation (enucleation) for 93 patients (24.6070), complete cyst resection in 69 patients (18.3070), partial cyst resection in 97 patients (25.7070), segmentectomy in 64 patients (16.9070), lobectomy in 48 patients (12.6070), and bilobectomy and pneumonectomy in one patient each (0.26070). Postoperative Complications These occurred in 44 patients (11.8070) and included prolonged air leaks in nine patients, atelectasis necessitating bronchoscopy in two patients, aspiration pneumonia in 11 patients, and empyema in four patients (table 5). There were two operative deaths (mortality rate, 0.53070); cause of death was cardiac arrest in one and respiratory failure in the other. During the follow-up period, active hydatid lung disease was found in only two patients (0.53070). They underwent a second pulmonary resection. One had lobectomy and one had segmentectomy; there were no postoperative complications and no operative deaths. The free interval between the first pulmonary resection and the discovery of the sec-
TABLE 5 POSTOPERATIVE COMPLICATIONS
Sites of Involvement There were 327 patients who had disease localized to the lung (table 4). Of these, 59 (15070) had extrapulmonary cysts of which 54 were hepatic, four renal, and one intraperitoneal. Lung cysts were unique in 286 cases (74.4%), multiple in 20 (5.1070), and bilateral in 21 (5.8070).
Complications
(n)
(%)
Wound infection Pneumonia Prolonged air leak Empyema Atelectasis Hydropneumothorax Total
17 11 9
38.6 25 20.4 9 4.5 2.2 100
4 2 1
44
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ond lung cyst was 27 and 39 months, respectively; the cyst was single, and the location was in the ipsilateral lobe in both cases. At the time of this report 420/0 of patients were living free of disease and had been followed for 12to 120months after discharge; 12% were lost to follow-up within 12months, 17% within 24 months, and 27% within 36 months. Nine (2%) patients died of other causes. Discussion
Hydatid disease is a widespread problem throughout the world, and the only effective treatment is surgical excision. It is prevalent in Tunisia, especially in central Tunisia. In this region echinococcosis caused by E. granulosus represents a zoonosis of major public health importance. The liver and lungs are most frequently involved (75% liver, 15% lung, and 10% the rest of the body) (1). In our area, lungs were involved in 35% (3). There may be geographic differences in organ distribution related to some biologic factors in parasite or host. Most cysts are acquired in childhood and are not diagnosed until the third or fourth decade (1,4,5). Cysts grow faster in compressible organs such as the lung, and this may account for the relatively high incidence of the disease in this organ in childhood (5). In children some series indicate that pulmonary involvement is more frequent than hepatic involvement (6). In our study more than one-third of patients werebetween 5 and 20 yr of age, and 58% were between 5 and 30 yr of age. Hydatidosis was more frequent in female than in male patients. The male-to-female ratio in our serieswas 0.74;higher incidence rates were observed in female patients in all age groups except for the 5- to 20-yr range. This predominance of hydatidosis in women is found in most reports from northern Africa (7, 8); this might to be due to sex-related behavioral differences with respect to direct and indirect exposure to dogs and dog feces. The cycle of E. granulosus is considered to be essentially rural, involving predominantly the sheep as the intermediate host and the dog as the definitive host (9). In our series only 42% of the patients were from rural areas; these results suggest strongly that in addition to the rural cyclethere is an urban cycle (10). The diagnosis of hydatid lung disease can frequently be suspected on clinical findings that are compatible with the disease in those who have had contact with an appropriate host.
Imaging techniques such as radiography, ultrasound, and nuclear scanning have enabled accurate localization and definition of lung lesion. Furthermore, serologic tests based on the host immune response to the Echinococcus organism have provided additional diagnostic tools. In our experience the most common clinical presentations were cough, hemoptysis, and chest pain. Allergic reactions are not as common as was once thought, although fatal anaphylaxis does occur (11). Twelvepatients (3%) had histories of allergic episodes after cyst rupture, but none had fatal anaphylaxis. The most serious usual complication of rupture is bacterial infection; 119 patients (31%) had symptoms of bacterial infection. Both rupture and infection can change the appearance of hydatid cyst. Although many of the presenting features are similar, the point of differentiation is the incidence of fever; patients with hydatid cyst are rarely febrile (12). Radiographs ofthe chest allow recognition of pulmonary cysts (13). Intact cysts are usually well demarcated (figure 1), although cysts have several different appearances. As the cyst enlarges, it erodes bronchioles, and air is introduced betweenthe pericyst and laminated membrane and appears as a thin, lucent crescent in the upper part of the cyst, producing the crescent or meniscus sign (figure
Fig. 1. Radiograph of the chest showing two well-defined cysts in the left lung.
2). In older and infected cysts, a thick cyst wall caused by adjacent atelectasis and reactive change can be seen on the radiograph, with the classic double-arch, or water-lily(figure 3) sign within hydatid cysts (14). Other imaging techniques, therefore, are needed to detect and evaluate possible extrathoracic hydatid cysts. Ultrasound is very sensitive in revealing cysts and in identifying certain characteristic features of hydatid disease (15). Currently, the most effective imaging technique available to us is the CT scan; it is highly sensitive, and it can discover additional small intrathoracic lesions. In addition, it plays a major role in the preoperative assessment of the disease (16, 17). Curvilinear or ringlike calcification, which can develop on the rim of the cyst, is more common in older cysts and in hepatic cysts. Of 58 patients who had hepatic cysts, calcification was visible on plain films in about 45%. These calcified cysts of the liver with negative clinical laboratory tests need no specific treatment. Calcification develops in thoracic cysts much less commonly (13, 17), 0.7% in our series. Blood eosinophilia is usually minimal or absent, but it may increase with episodes of cyst leakage. It occurs in about 40% of patients (18). Serologic testing is the method of choice to corroborate the diagnosis (19).
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JERRAY, BENZARTI, GARROUCHE, KLABI, AND HAYOUNI
Fig. 2. Chest radiograph showing the typical meniscus sign. Air outlines the pericyst (arrows).
There are now many sensitive and specific serologic tests available such as indirect hemagglutination, indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and latex fixation. Although these assays are sensitive, false-positive reactions can occur, most commonly in patients with other helminthic infections. Negative serologic tests do not exclude the diagnosis of echinococcosis (20). Of the serologic tests, immunoelectrophoresis has been found to be the most sensitive (75070 posi-
tivity compared with 54.1% for indirect hemagglutination). False-negative results occur mostly with unruptured cysts, especially in children (2). Surgery is the treatment of choice. A variety of approaches have been described. Cystectomy consists of removal of the endocyst only and leaves behind the pericyst; the parasite is enucleated intact by gentle dissection (21).Partial and total pericystectomy eradicates the parasite without damaging healthy parenchyma, and it leaves a clear-cut section be-
Fig. 3. Large ruptured cyst in left lung (arrow); the parasite lies collapsed (arrowhead) within it showing the pathognomonic "water-lily" sign of ruptured hydatid cyst.
hind; the residual pericyst may be left open or obliterated by capitonnage, which consists of stitching the remaining lung cavity (22). Segmentectomy, lobectomy and pneumonectomy may also be carried out when lung tissue is diffusely involved. In the group of patients with ruptured and infected cysts, 87% were treated by lung resection, and postoperative complications were more common (39 of 44 complications occurred in the latter group). In the group of patients with intact cysts, only five complications were seen. The difference in complication rates between these two groups is statistically significant. Mean hospital stays for these groups were, respectively, 27 and 11 days (p < 0.0001). Medical therapy of hydatid disease is difficult to evaluate, although high-dose mebendazole has been reported to be effective in some patients (23-25). In our experience three women unfit for surgery were treated medically, one with mebendazole and two with flubendazole. They were placed on several courses of drugs, 6 g/day. One 54-yr-old patient was treated with mebendazole for 4 yr. In this patient the response to therapy was slow, with mild clinical improvement. She was last seen in September 1990. She continues to have expectoration of cyst fluid, membranes, and scolices; a chest radiograph showed multiple-ruptured cysts in both lungs. The two latter patients (26 and 34 yr of age, respectively) received flubendazole 6 g/day; they were lost to follow-up after only 3 months of observation. The present study indicates that the hydatid recurrence rate is 0.5%. Unfortunately, there is remarkably little data in the literature on recurrence rates for lung hydatids. Chevret and coworkers (26) have reported a recurrence rate of 2.9% in 1,397 patients. On the basis of our experience, the following conclusions can be made. (1) Lung hydatidosis is predominantly a disease of the young and of the middle-aged adult. (2) This disease should be suspected in patients from endemic areas. (3) The diagnosis of a hydatid cyst of the lung is an indication for the examination of the liver because multiple echinococcal cysts are common and ultrasound has a high accuracy in the diagnosis of the lesion. (4) Immunoelectrophoresis is the most sensitive diagnostic test. (5) To date no effective medical treatment is available, and surgery remains the best hope for cure. (6) A health education program adapted to the specific sociocultural tra-
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ditions is needed to promote preventive measures. References 1. Saidi E Surgery of hydatid disease. Philadelphia: W. B. Saunders, 1976. 2. Radford AJ. Hydatid disease. In: Weatherall DJ, Ledingham JGG, Warrel DA, eds. Oxford textbook of medicine. Oxford: Oxford University Press, 1982; 5442-4. 3. Kehila M, Ammar N, Hattab Ch, et al. Etude statistique de localisations hydatiques. Tunis Med 1988; 66:587-91. 4. Carcassone M, Aubrespy P, Dor V, Choux M. Hydatid cysts in childhood. Prog Pediatr Surg 1973; 5:1-35. 5. Bloomfield JA. Hydatid disease in children and adolescents. Australas Radiol 1980; 24:277-83. 6. Matsaniotis N, Karpathios T, Koutoyzis J, et al. Hydatid in Greek children. Am J Trop Med Hyg 1983; 32:1075-8. 7. Benhailes N, Ouchfoun A, Chkarine V. Evaluation d'une annee de mise sous surveillance epidemiologique de I'hydatidose. Bull Epidemiol INSP (Alger) 1981; 1-22. 8. Laouar M. Aspects epidemiologiques actuels de l'hydatidose humaine dans l'est algerien. These pour Ie doctorat en sciences medicales, Alger 1987.
9. Euzeby J. Les echinococcoses animales et leurs relations avec les echinococcoses de I'homme. Paris; Vigot, 1971. 10. Bchir A, Jaiem A, Jemmali M, Rousset 11, Gaudebout C, Larouze B. Possible existence of an urban cycle of Echinococcusgranulosisin central Tunisia. Trans R Soc Trop Med Hyg 1987; 81:650. 11. Beggs I. The radiologic appearances of hydatid disease of the liver. Clin Radiol 1983; 34:555-63. 12. Altemeier WA, Schowengerds CG, Whiteley DH. Abscesses of the liver: surgical considerations. Arch Surg 1970; 101:258-66. 13. Beggs I. The radiology of hydatid disease. AJR 1985; 145:639-48. 14. Ramos L, Hernandez-Mora M, IIIana M, Liorente MT, Marcos J. Radiological characteristics of perforated pulmonary hydatid cysts. Radiology 1975; 116:539-42. 15. David B, Lewall MD, Scott J, McCorkell MD. Hepatic echinococcal cysts: sonographic appearance and classification. Radiology 1985; 155:773-7. 16. Diego Choliz J, Lecumberri Olaverrif J, Franquet Casas Ostiz Zubeita S. Computed tumography in hepatic echinococcosis. AJR 1982; 139: 699-702. 17. Saksouk FA, Fahl MH, Rizk GK. Computed tomography of pulmonary hydatid disease. J Comput Assist Tomogr 1986; 10:226-32. 18. Balikian JP, Mudarris FE Hydatid disease of
the lungs: a roentgenologic study of 50 cases. AJR 1974; 122:692-707. 19. Schantz PM, Kagan IG. Echinococcosis (hydatidosis). In: Houba V, ed. Immunologic investigation of tropical parasitic disease. New York: Churchill Livingstone, 1980; 104-29. 20. Scully RE, Mark EJ, McNeely WF, McNeely BU. Case records of the Massachusetts General Hospital. N Engl J Med 1987; 317:209-18. 21. Slim MS, Khayat G, Nasr MT, Judejian YD. Hydatid disease in childhood. J Pediatr Surg 1971; 6:440-8. 22. Sarsam A. Surgery of pulmonary hydatid cysts. J Thorac Cardiovasc Surg 1971; 62:663-8. 23. Bekhti A, Schaaps JP, Capron M, et al. Treatment of hepatic hydatid disease with mebendazole: preliminary results in four cases. Br Med J 1977; 2:1047-50. 24. Beard CT, Rickard MD, Goodman HT. Medical treatment for hydatids. Med J Aust 1978; 1:633-5. 25. Bryceson ADM, Cowie AGA, Mcleod C, et al. Experience with the treatment of inoperable hydatid disease in England. Trans R Soc Trop Med Hyg 1982; 76:510-8. 26. Chevret R, J ouharia A, Rahali R. Kysteshydatiques du poumon. Le problerne des recidives. Chirurgie 1980; 106:673-82.
