Surgical aspects of pulmonary aspergillosis

Surgical aspects of pulmonary aspergillosis Twenty-one cases of pulmonary aspergillosis managed surgically over a 13 year period in the Missouri State Chest Hospital were reviewed. Postoperative complications occurred in 11 patients (52 per cent) but were mostly manageable by conservative measures. There was one postoperative hospital death due to respiratory failure. With the lack of an effective and safe antifungal drug, resection is the treatment of choice for suitable candidates. In conclusion, some guidelines were drawn for the management of patients with this disease.

Salim B. Saab, M.D.,* and Carl Almond, M.D.,** Columbia and Mt. Vernon, Mo.

AspergillUS is the generic name coined by Micheli in 1729 for the fungus molds he observed. Virchow- (1856) was the first pathologist to describe the role of aspergilli in human pulmonary disease, but human aspergillosis was discussed in the earlier studies of Sluyter ( 1847) and Bennett (1842) .1-:1 Among the various species identified to date, Aspergillus [umigatus is of particularly growing importance in pathogenicity involving the respiratory system. It is ubiquitous in distribution and saprophytic in nature. The purpose of this paper is to report 21 cases of pulmonary aspergillosis managed surgically at the Missouri State Chest Hospital during a 13 year period. We shall review the clinical features and hence try to define the present status of surgery in the management of this disease. Materials and methods

Between July, 1960, and June, 1973, 21 patients with pulmonary aspergillosis had primary thoracic operations to control the Received for publication May 13, 1974. * Assistant Professor of Surgery, University of Missouri Medical Center, Columbia, Mo. 65201, and Associate Chief of Surgery, Missouri State Chest Hospital, Mt. Vernon, Mo. 65712. ** Professor of Surgery; Chief, Section of Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo. 65201.

infection. The criteria for diagnosis were ( 1) repeated isolation of the organism in sputum cultures and (2) identification and growth of the organism from surgical specimens. There were 14 men and 7 women, a ratio of 2: 1. Ages ranged between 23 years and 68 years, with persons between 50 and 59 years having the highest incidence of the disease (48 per cent) (Table I). Hemoptysis, the leading symptom, occurred in 62 per cent of the cases. Other symptoms included cough, weight loss, fatigue, chest pain, fever, and dyspnea, in decreasing order (Table II). Table III summarizes the diagnostic tests performed. The tuberculin skin test was positive in 52 per cent and the histoplasmin skin test in 58 per cent. Both tests were positive in 29 per cent and both were negative in 20 per cent. The complement fixation test for aspergillosis was done in 13 cases. It was positive in 4 and negative in 9. The fungus was repeatedly grown by sputum culture in 8 of 20 cases (40 per cent); culture was not attempted in 1 patient. The diagnosis was confirmed by histopathology of the tissue removed during the operation in 20 patients (95 per cent). There was no tissue specimen in 1 patient who was treated by thoracoplasty. Bronchoscopy yielded positive information in 1 455

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Table I. Age Decade

No.

Per cent

20-29 30-39 40-49 50-59 60-69 Totals

3 3 3 10 2 21

14 14 14 48 10 100

Symptoms

No.

Per cent

Hemoptysis Cough Weight loss Fatigue Chest pain Fever Dyspnea

13 12 9 6 5 5 4

62 57 43 29 24 24 19

Table II. Symptoms

out of 10 patients on whom the procedure was performed. It showed obliteration of the orifice of the right upper lobe bronchus. Bronchography showed a destroyed right lung with bronchopleural fistula in 1 patient. Pulmonary function tests showed moderate respiratory impairment in 5 patients (19 per cent). The majority of patients presented radiographically with cavitary disease (90 per cent, or 19 cases), whereas 2 patients had a pneumonic infiltrate. Four patients had involvement of more than one lobe, and I patient had bilateral disease. Fungus balls were present in 11 patients with cavitary disease. One patient had 2 aspergillomata. The lesions were demonstrated by plain chest roentgenography in most cases, or else by tomography. They were all located in the upper lobes, except in 1 case in which the superior segment of the left lower lobe was involved (Table IV). Fourteen patients had one or more diseases associated with aspergillosis. Tuberculosis and bronchiectasis were the most frequent (Table V). The primary major thoracic surgical procedures included six segmental resections, eight lobectomies, four bilobectomies, two pneumonectomies, and one thoracoplasty.

The latter was done on a patient with poor respiratory reserve, and one of the pneumonectomies was done because of associated squamous cell carcinoma (Table VI). Table VII summarizes the indications for surgery in the whole group. The main indication found in 11 patients (52 per cent), was recurrent or severe hemoptysis. Cavitary disease of unknown etiology was the next most frequent indication in 6 patients, 2 of whom had fungus balls. Cavitary histoplasmosis, unresolved pulmonary infiltration, atypical tuberculosis, and bronchopleural fistula with empyema constituted the indication for surgery in 1 patient each. Results

Eleven patients (52 per cent) developed a total of thirteen complications in the postoperative period. The most common complication was a residual pleural space (in 5 patients), and the most serious was a bronchopleural fistula (in 3 patients) (Table VIII). A bronchial fistula was corrected by thoracoplasty in 1 patient. The second patient refused further surgery and died 2 112 years later of contralateral disease with aspergilloma and massive bleeding; he had failed to respond to amphotericin B therapy on two occasions. The third patient died 3 weeks postoperatively of pneumonia and respiratory insufficiency. All other complications responded to conservative measures. There were 5 patients with residual spaces. The space disappeared during follow-up in 1, decreased markedly in size in 2, and persisted in 2 patients, but with no related symptoms. The follow-up period ranged between 2 months and 9 years. Two patients were lost to follow-up but were in improved condition at the time of discharge. Of the remaining 19, 12 patients (63 per cent) were doing well and free of symptoms. Two others were in improved condition but had some residual symptoms related to the underlying disease. There was a total of five deaths during the follow-up period. Two of them were discussed above. One of these deaths was

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Table III. Diagnostic tests Test

Per cent

Purified protein derivative Histoplasmin skin test Complement fixation Sputum cultures Histopathology Bronchoscopy Bronchogram Pulmonary function tests

II

12 4 8 20 1 I 4

52 57

10

19

9

38

12

48 38 43 57

95 5 5 19

0 9

43

8

2 14

0 9

67

0 I

8 1

0

5 38 5

I

5

11 18 3

52 86 14

Table IV. Localization and type of lesion Right lung lobes Type oj lesion

Upper

Middle

Lower

Cavitary disease With fungus ball Without fungus ball Infiltration

5 3

0 3

I

Totals

9

1 4

0 2 0

definitely due to progression of the disease to the other side, and we believe the outcome could have been prevented had the patient accepted further surgery. The second may be labeled a hospital death; however, the patient had borderline pulmonary function, and a bilobectomy was performed because of a strong suspicion of carcinoma. Otherwise he would not have been a suitable surgical candidate. The third patient had atypical tuberculosis (Mycobacterium kansasii) with cavitary disease and an aspergilloma. An uncomplicated lobectomy was performed, and his sputum cultures were negative after the operation. He died 21 months later with gram-negative septicemia and shock. The fourth death occurred 9 months postoperatively as a result of acute pulmonary embolism. This patient was the only one to be treated with thoracoplasty because of mixed impairment of pulmonary reserve secondary to emphysema, chronic alcoholism, and bilateral upper lobectomies performed previously for tuberculosis. The cause of death was not known in the fifth patient, who died 4 years after segmental resection of the left upper lobe. However, re-evaluation 9 months post-

2

Total No. oj lobes

5 5 0 10

I 0 0

1

11 13 2 26

operatively revealed improvement on chest x-ray study and sputum cultures negative for Aspergillus. The last 3 deaths, therefore, were not related to the operation or aspergillosis. Discussion

Four clinical forms of aspergillosis have been described": (1) bronchial, with or without allergic manifestations; (2) disseminating; (3) bronchopneumonic; and (4) intracavitary. The last two forms are of particular interest to the thoracic surgeon. Although some authors believe that aspergillosis may be a primary disease in a few cases," " in most instances it is a saprophytic infection superimposed on other chronic debilitating diseases or predisposed to by drugs that depress the body defenses." The fungus can also colonize pre-existing pulmonary cavities or areas of infarction or necrosis, and it has been reported in association with a wide spectrum of chest diseases, including tuberculosis, bronchiectasis, histoplasmosis, sarcoidosis, bronchogenic carcinoma, bronchogenic cysts, pulmonary infarcts, lung abscess, bronchopneumonia, emphysema, and ankylosing spondylitis.': '-H

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Table VII. Indication for surgery

Table V. Associated diseases Type oj disease

No.

Tuberculosis Bronchiectasis Histoplasmosis Bronchogenic carcinoma Emphysema Interstitial pneumonitis Hiatus hernia Hypothyroidism Myocardial infarction Chronic alcoholism Carcinoma in situ of cervix

5 3 I I I I I I I I 2

18

Total

Table VI. Primary pulmonary operations Type oj operation

No.

Segmental resection Lobectomy Bilobectomy Pneumonectomy Thoracoplasty

6

Totals

Per cent

s

29 38

I

10 4

21

100

4 2

Indication Hemoptysis With cavity and ball With cavitation only With bronchogenic carcinoma Totals

No.

I Per cent

7

3 I 11

Cavitary disease Undiagnosed With fungus ball

4 2

Totals

6

52

28

Cavitary histoplasmosis with ball

5

Unresolved infiltrate

5

Atypical tuberculosis with ball

5

Bronchopleural fistula and empyema

5

19

Toxic substances and proteolytic enzymes have been isolated from the organism and are believed to contribute to the pathogenicity in infected tissues. Ill. 11 Since the description of the radiographic appearance of an intracavitary aspergilloma by Dcve'" in 1938, experience with this mycetoma has been described with increasing frequency. It is actually the most extensively reported type of aspergillosis. ~ Characteristically, the lesion appears as an intracavitary mass separated from the surrounding lung by a crescent of air. It may move depending on the patient's position. The mass is formed by a conglomeration of septate hyphae and is usually located in the upper lobes of the lungs.": x. n, J;'. 11 Tomograms of the chest will usually show the solid mass when the appearance on the plain chest film is not typical. For the diagnosis to be made, it is essential for the physician to consider aspergillosis in the differential diagnosis of other entities. Symptoms are not distinctive. However, the incidence of hemoptysis is very high (50 to 85 per cent), and the compli-

cation is recurrent and sometimes of massive proportions.':" 1:<. H Repeated isolation of the fungus from the sputum of a patient with cavitary pulmonary disease is highly suggestive of pulmonary aspergillosis, particularly if a fungus ball is seen radiographically. However, sputum cultures may be negative if the corresponding bronchus is blocked or if the colonized cyst is noncommunicating. l. t r, ", Precipitin and complement fixation tests are likely to be positive during the course of infection and shortly thereafter.': "'.'S If a patient with aspergilloma has skin hypersensitivity (aspergillin skin test), the physician must suspect coexistent allergic hypersensitivity. I . A definite diagnosis is established by demonstrating the organism and culturing it from resected specimens. In patients with calcified aspergilloma the fungus is dead and therefore cannot be cultured, but it can be identified after decalcification. ", Although a few cases of pulmonary aspergilloma may resolve spontaneously," " the frequency and unpredictable severity of hemoptysis in patients with the disease, together with the grave consequences of invasion or dissemination, call for an adequate therapy. The mortality rate in untreated patients is high. r , " 1:

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Table VIII. Postoperative complications listed by surgical procedure Complication Apical space Bronchopleural fistula Atelectasis Pleural effusion Wound dehiscence Paralytic ileus Total

I Lobectomy IBilobectomy I

Segmental resection

I Pneumonectomy I

Thoracoplasty

0 0 0 0 0 0

0 0 0 0 0 0

0

0

I 2

1

1 0 I I

I 0 0 0

3 0 0 I 0 0

6

3

4

I

Of the antifungal drugs, iodides, amphotericin Band Natamycin have been administered both systemically and by local instillation, with variable degrees of success. r-». D. 11. ""-".-, Gerstl"1I (1948) is credited with the first surgical resection for pulmonary aspergillosis. Several reports since then indicate that resection is the treatment of choice for patients with pulmonary aspergilloma unless other factors make the risk prohibitive.'" 1:<. 11 The extent of resection depends on the extent of pathology, including that of the underlying disease. Lobectomy is the preferred procedure, but segmental resection may be indicated in patients with impaired respiratory reserve. The experience with amphotericin B has not been uniformly encouraging.':': "' Three of our patients in this series received amphotericin B but eventually required surgery. One patient who had an operation on one side later died of massive bleeding with a fungus ball that developed on the other side, in spite of two adequate courses of amphotericin B therapy. Kilman and colleagues," in a presentation of 14 cases and a review of 70 cases reported in the literature until 1969, found a surgical mortality rate of less than 7 per cent. Postoperative complications depend largely on the magnitude and extent of the underlying disease and can be managed successfully in most cases. 1 I A relatively high incidence of residual pleural spaces and bronchopleural fistulas has been reported after resectional surgery.' I. "'-III Small residual pleural spaces have not been clinically significant in our

Total

5 3 2

1 I

1 13

experience. However, they should be followed carefully to detect and manage infection if it occurs. With improved surgical techniques, the incidence of postoperative bronchopleural fistula may be expected to decrease. However, the appearance of a fistula may indicate a poor healing capacity of a diseased bronchus and raises the possible advisability of preoperative coverage with antifungal drugs in selected patients." Furthermore, a fistula could still be handled by other available surgical procedures. Bilateralism of disease does not contraindicate surgical resection unless the disease is diffuse, for a staged approach is feasible. In conclusion, we believe the following are useful guides in the management of pulmonary aspergillosis: 1. Resectional surgery is the treatment of choice (a) for symptomatic localized disease in suitable candidates, (b) for cases in which the diagnosis is in doubt and there is a need to diagnose or exclude other serious or treatable conditions, and (c) for cases in which resection helps in the treatment of an underlying pathology. 2. Elective surgery for pulmonary aspergilloma may be performed in the good-risk, asymptomatic patient to prevent possible fatal sequelae in the future. J:l 3. If medical therapy is chosen, then "medical failures" who are suitable candidates should be given the benefit of surgery. It is hoped that continued research may yield an effective and relatively safe fungicidal drug. 4. Conservative watchful management is not justifiable in good-risk patients with aspergilloma, for the potential hazards by far

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exceed the occasionally observed benign course. 5. Local instillatilon of antifungal agents is helpful for the patient with impaired pulmonary function or other illnesses that place him in a high-risk category for resection. 6. When aspergillosis complicates malignant and terminal illnesses, it is the natural course of the latter that decides the outcome.

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