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Surgery in pulmonary aspergillosis
Surgery in pulmonary aspergillosis Pulmonary aspergillosis is a rare disease, most commonly presenting as secondary invasion of pre-existing cavitary disease. In Toronto General Hospital 24 patients have been recognized as having this disorder in the 10 years from 1965 to 1975. The most common presenting symptoms were cough, sputum production, and hemoptysis, with the hemoptysis occasionally being massive. Tuberculosis and bronchiectasis were the commonest pre-existing diseases. Thirteen of these patients were treated by surgical resection because of major complications or progression of the aspergillosis. Five of these patients died following surgery, all of these having had major complications prior to surgical intervention. OJ the eight surviving patients seven are progressing well, but one has developed further extension of his disease.
R. D. Henderson, 1. Deslaurier, E. L. Ritcey, N. C. Delarue, and F. G. Pearson, Toronto, Ontario, Canada
The fungus Aspergillus [umigatus, despite its ubiquitous nature, very rarely gives rise to human infection. The first recognized aspergillosis infection was reported by Sluyter' in 1847 and the first operative resection of an aspergilloma was carried out by Gerstl, Wideman, and Newmann- in 1948. Kilman and associates" in 1969 reviewed the world literature and reported a total of only 70 resections, adding 14 further cases of his own. This rare disease continues to present as a major therapeutic challenge. Case material Twenty-four patients have been diagnosed as having aspergillosis at the Toronto General Hospital between the years 1965 to 1975. The average age of these patients is 42 years, 15 are male and 9 female. In all cases a diagnosis was made either by sputum culture or by the recognition of Aspergillus [umigatus in a resected specimen. From the Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Read at the First Annual Meeting of The Samson Thoracic Surgical Society, Santa Barbara, Calif., May 28-30, 1975.
Address for reprints: Dr. R. D. Henderson, Rm 139, University Wing, Toronto General Hospital, Toronto, Ontario, M5G IL7, Canada.
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Twenty patients had cough and sputum production and in three of these the sputum production was massive. Eleven patients had hemoptysis and in four of these the hemoptysis was recurrent and massive. Other symptoms which occurred included pyrexia in four patients, weight loss in excess of 50 pounds in 4, and chest pain localized to the site of major involvement in 5 (Table I).
In those with massive sputum production the sputum had an offensive taste and odor and produced considerable distress to the patient. Although in many the hemoptysis was marked and distressing, in only four was it characterized as being massive and in these four patients bleeding episodes of several hundred cubic centimeters occurred, producing acute respiratory distress in two patients, in one a respiratory arrest requiring emergency bronchoscopy and suction, and in one a cardiac arrest. All patients had chest x-rays. In most patients tomograms were also performed and in a few more complicated radiological studies such as bronchography and pulmonary angiography were carried out. On reviewing the radiological studies 12 were considered to be nonspecific, showing diffuse lung infiltration which was not suffi-
Volume 70 Number 6
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Pulmonary aspergillosis
December, 1975
Fig. 1. A. F., age 36, has typical radiological features. He had known tuberculosis, treated successfully 5 years previously. Hemoptysis of moderate severity had been present for 2 years. At the right apex he has a cavitary lesion with a small fungus ball. Right upper lobectomy has successfully removed his aspergilloma and stopped the hemoptysis.
ciently characteristic to allow for diagnosis. In one patient a bulla was recognized but the presence of aspergillus in this bulla was not evident. Eleven patients had a typical radiological mass with cavitation and a recognizable fungus ball and air crescent most characteristic of aspergillosis (Fig. 1). Fifteen of the 24 patients had aspergillus cultured from their sputum. Six patients had serological studies which were positive. Aspergillus is recognized as complicating pre-existing pulmonary disease, usually of a cavitary type. In the patients seen, 22 of the 24 had an underlying disease considered to be a significant etiologic factor. Eight of these had tuberculous cavities, five had bronchiectasis, two had sarcoid, and two had silicosis. Other diseases occurring in individual patients were asthma , ankylosing spondylitis, pulmonary radiation, scleroderma, and an empyema cavity secondarily infected by aspergillus. One patient was terminally ill from hepatitis and the aspergillosis was considered to be related to an altered immunological mechanism. Seventeen patients have had surgical procedures. In three a lung biopsy was obtained
Table I. Symptoms in 24 patients with pulmonary aspergillosis" Symptom
Cough and sputum Massivesputum Hemoptysis Massivehemoptysis Pain Pyrexia Weight lossgreater than 50 pounds
4
• A wide variety of symptoms were present, but cough , sputum production, and hemoptysis predominated.
for tissue diagnosis by limited thoracotomy but no attempt was made at resection. In one patient a tracheostomy was done at the time of respiratory failure which eventually proved to be terminal. Thirteen of the 24 patients have been treated by major lung resection. In these 13 patients the radiological features were classified in the manner reported by Belcher and Plummer.' with this classification aspergillosis was subdivided into allergic aspergillosis, aspergillomas, and suppurative aspergillosis. No patient with allergic aspergillosis was treated surgically. Aspergillomas were di-
1 09 0
Henderson et al.
The Journol of Thoracic and Card iovascular Surgery
Fig. 2. Patient F., age 60, presented with typical radiological changes present at both apices. On the left a large fungus ball was present in a pre-existing tuberculous cavity . A crecent of air can be seen on the upper surface of the fungus mass. This would be classified as bilateral complex aspergillomas.
vided into simple and complex, depending on their radiological appearance. The sim. pIe aspergilloma was considered to be an infection complicating a thin-walled cyst of bronchial origin in which there was little or no abnormality in the surrounding lung tissue. A complex aspergilloma was considered to develop in a pre-existing cavity produced by some form of destructive lung disease such as tuberculosis. In this case the lesion was in the cavity but the surrounding lung tissue showed evidence of established disease. According to this classification, one of the patients operated upon had a simple aspergilloma, 10 had complex aspergillomas, and two had suppurative aspergillosis. The patients operated upon were treated surgically because of severe and progressive symptomatology or because of major and rapidly progressing complications . In the one case of a simple aspergilloma surgical resection was undertaken because of the presence of the bulla and the aspergillosis was not recognized until examination of the resected specimen. This method of selection has resulted in the majority of patients
operated upon being of very high operative risk because of advanced pulmonary disease. One patient had a wedge resection of an apical aspergilloma . Eight patients were treated by lobectomy and four by pneumonectomy. In those treated by lobectomy three required thoracoplasty because of an inexpansile lower lobe. Five of the 13 patients treated surgically died of complications directly related to their disease or to the operative procedure. This very high mortality rate compares with less than 4 per cent in the same unit for lung resection in patients with bronchogenic carcinoma. Undoubtedly a contributing factor to this mortality rate is the extreme debility of many of these patients treated and the emergency nature of the surgical resection which proved necessary. In one patient pneumonectomy was performed for extensive and unilateral suppurati ve aspergillosis. This patient died on the seventh postoperative day from a major hemorrhage related to a bronchoarterial fistula. Two patients had acute respiratory failure requiring ventilatory care following masssive hemoptysis and resection was necessary because
Volume 70 Number 6 December, 1975
Fig. 3. Patient F., following resection and left thoracoplasty, developed a residual space above his inexpansible left lower lobe. Chronic tube drainage of this space gave satisfactory control of his symptoms for 2 years.
of continued bleeding. Although bleeding was controlled by surgical resection, their respiratory failure was not reversible. One patient had two massive hemoptyses followed by cardiac arrest and at the time of a third hemoptysis a lobectomy was done as an emergency procedure. He died following a massive myocardial infarct and cardiac failure 10 days following resection. The final patient who died had involvement of his aortic arch by aspergillosis and at the time of resection the aortic arch was opened and required prosthetic replacement. He had a delayed thrombosis in the graft and died following this complication. Two of the patients dying had pneumonectomies and three had been treated by lobectomy. Of the eight surviving patients three had uncomplicated lobectomies and five required extensive and difficult resection because of very dense pulmonary adherence or direct growth of the aspergilloma through and into the chest wall. A thoracoplasty was necessary in three because of poor expansion of the residual lung tissue.
Pulmonary aspergillosis
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Fig. 4. Patient F. developed a complex aspergillorna at the base of his right lung. This has occurred 2 years following left upper lobectomy.
Follow-up of surgical patients ranges from 2 to 48 months and averages 20 months. With one exception those patients with resected disease are progressing well and show no evidence of dissemination of their aspergillosis. One patient (Fig. 2) has a residual apical pleural space requiring long-term tube drainage (Fig. 3) . He has developed a complex aspergilloma in the right lower lobe 2 years following his initial resection and his respiratory function has further deteriorated (Fig. 4). Discussion Pulmonary aspergillosis may present clinically in a variety of ways.":' It may present as a radiological density which is nonspecific and requiring diagnosis. It may present as a complication of recognized and preexisting pulmonary disease with invasion of damaged lung tissue.H In a significant percentage of patients the presentation is one of progressive pulmonary infection or of massive hemoptysis. In this particular group of patients management is extremely difficult and if surgery is undertaken the operative mortality rate is high. Established methods of diagnosis include
The Journal of
10 9 2
Henderson et al.
Thoracic and Cardiovascular Surgery
the recognition of the pre-existing disorder and with this the realization that alteration in the radiological appearance may well be related to a secondary aspergilloma. The radiologic features are a composite picture of pre-existing lung disease and the superadded changes related directly to an aspergillus infection. The most characteristic radiological changes are those of a fungus ball with an associated crescent of air. The fungus ball by itself is not diagnostic in that this can be mimicked by necrotic tissue of any source lying within the cavity. Alternate sources of such necrotic debris include blood clot and carcinoma, or a ruptured hydatid cyst. When followed over a period of several weeks most necrotic tissue will be broken down and coughed up, giving alteration in the appearance of the central mass. This alteration is rarely seen in aspergillosis over such a short period of time." By changing the position of the patient it may be possible to show movement of the fungus ball and by this maneuver demonstrate its position within the lumen of the cavity. Sputum culture is frequently positive in that the aspergilloma being free within the cavity is communicating with the tracheobronchial tree and constantly shedding filaments of fungus. Skin tests are of little value, however, serology is diagnostically significant and should be used to confirm the presence of an aspergillus infection. o, 10 Drug therapy has not proved to be of much value but the drug of choice is amphotericin BY, 12 There is no indication that this drug has any value in the patient with a solitary fungus ball but it has been used in far-advanced and complicated fungal infections and in these situations has been reported to be of some clinical value. Surgical resection has been reserved mostly for progressive aspergillosis and for those in whom the complications of the disorder are life threatening."?" With this method of selection in the 13 patients treated with major pulmonary resections many of those treated surgically were found to have extremely advanced disease and indeed many had reached the stage where surgery
was the only hope of controlling their complications. Under these circumstances the surgical mortality rate has proved to be extremely high. In other reported series the mortality rate is considerably lower; however, this would appear to be related to the severity of the pre-existing disorder at the time of resection. REFERENCES Sluyter, T.: De Vegetalibus Organisrni Animalis Parasitis, Diss. Maug. Berolini, p. 14, 1847 (cited by Renon, 1897). 2 Gerst!, B., Wideman, W. H., and Newmann, A Y.: Pulmonary Aspergillosis: Report of 2 Cases, Ann. Int. Med. 28: 662, 1948. 3 Kilman, J. W., Changoo, A, Andrews, M. D., and Klasser, K.: Surgery for Pulmonary Aspergillosis, J. THORAc. CARDIOVASC. SURG. 57: 642, 1969. 4 Belcher, 1. R., and Plummer, N. S.: Surgery in Broncho-pulmonary Aspergillosis, Br. J. Dis. Chest 54: 335, 1960. 5 Pesle, G. D., and Monod, 0.: Bronchiectasis Due to an Aspergilloma, Dis. Chest 25: 172, 1954. 6 Saliba, A, Pagnini, L., and Beatty, O. A: Intracavity Fungus Balls in Pulmonary Aspergillosis, Br. J. Dis. Chest 55: 65, 1961. 7 Bruce, R. A: Case of Pulmonary Aspergillosis, Tubercle 38: 203, 1960. 8 Irwin, A.: Radiology of the Aspergilloma, Clin. Radiol. 18: 432, 1966. 9 Henderson, A H., English, M. P., and Yecht, R. J.: Pulmonary Aspergillosis. A Survey of Its Occurrence in Patients With Chronic Lung Disease and a Discussion of the Significance of Diagnostic Tests, Thorax 23: 513, 1968. 10 Longbottom, 1. L., and Pepys, J.: Pulmonary Aspergillosis: Diagnostic and Immunological Significance of Antigens and C-Substance in Aspergillus [umigatus, 1. Pathol. Bacteriol. 88: 141, 1964. 11 American Thoracic Society Committee of Therapy: Am. Rev. Resp. Dis. 86: 784, 1967. 12 Peer, E. T.: Case of Aspergillosis Treated With Amphotericin B, Dis. Chest 38: 222, 1960. 13 Schwartz, J., Baum, G. L., and Straub, M.: Cavitary Histoplasmosis Complicated by Fungus Ball, Am. J. Med. 31: 692, 1961. 14 Davies, D.: Pulmonary Aspergillosis, Can. Med. Assoc. J. 89: 392, 1963. 15 Foushee, J. H. S., and Norris, F. G.: Pulmonary Aspergillosis, J. Thorac. Surg. 35: 542, 1958. 16 Peccra, D. Y., and Toll, M. W.: Pulmonary Resection for Localised Aspergillosis, N. Eng!. J. Mee!. 263: 785, 1960.
Volume 70
Pulmonary aspergillosis
Number 6 December, 1975
Discussion DR. JOHN B. GROW, SR. Denver, Colo.
I think that it is very appropriate that we should have a paper like this in a meeting that is so heavily weighted in cardiac surgery. As Dr. Lawrence said this morning, most of us spend our time sewing veins to various structures and pay little attention to the chronic infections of the chest which we used to see so much. When I was told that I could discuss this paper, I hurriedly looked through our cases to see how many cases we have had, and in 40 years I have seen eight patients operated upon. So it is not just something you see every day. I think that this shows us what we learned from the surgical treatment of tuberculosis a good many years ago, and that is that if you cannot control the organism, your surgical results are going to be poor. Before the advent of streptomycin, ionase, and the other drugs, we did a very good job of our surgery in tuberculosis, particularly resection. I think in a way this is analogous. Since the results of amphotericin B are at best unreliable, and we do not have any other drug that will really be effective in this disease, we can anticipate poor results following resection. One of the other problems we have is that our diagnostic facilities are not the best. We depend on sputum culture. Actually, tissue examination is the most reliable means of examining the lung, and we do not really find that out until surgery. So that if we did not want to use prophylactic amphotericin B, most of the time we would end up not making the diagnosis until the chest is open. Of our eight patients, all survived, but two had empyema. I thought that perhaps I might address the problem of what to do with empyema since these two empyemas were something of a problem. Those of you who have seen empyema following aspergillus infections know what I am talking about. You look inside the pleural space, and there is a thick coating of white substance that looks like coating on a cake, and when you lift this off, it leaves an inflamed bleeding surface. These things just do not heal, and so if you have such a problem, you have to make up your mind what you are going to do about it. The way we decide to treat it was by giving intravenous amphotericin B and peeling this peel off and then spraying the inside of the cavity with an amphotericin B solution. In both instances, the white peel did eventually disappear after IO days to 2 weeks, and we were able to go ahead with thoracoplasty and obliterate the space.
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I think when such complication occurs, that you do have to go ahead and realize that the chance of the thing healing as empyema would heal is almost nil. DR. RANDALL B. GRIEPP Stanford, Calif.
I enjoyed this paper very much, and I rise to mention another group of patients in whom aspergillus can be a problem. This is the increasingly large number of patients that have been treated with toxic drugs for cancer chemotherapy or for organ allograft rejection. Pulmonary aspergillosis is becoming an increasingly difficult diagnostic and therapeutic problem in these patients. I would like to mention 18 cases of premortemdiagnosed pulmonary aspergillosis that we have encountered in the past 7 years in a total of 84 heart transplants. In all of these patients, owing to their compromised immunocompetence and poor tissue healing, we did not want to proceed with diagnostic or therapeutic modalities that involved thoracotomy. As a consequence, we relied heavily on the routine sputum culture, the transtracheal aspirate, and the direct lung aspirate. I would like to discuss this latter technique in a little more detail. In 14 of these 18 cases, direct lung aspirates were carried out and positive diagnoses were obtained in all 14. Aspiration of pulmonary nodules is a relatively simple procedure involving passing an 18 gauge thin-wall needle directly into the lesion under fluoroscopic control. A sample is aspirated from the lesion, some preservative free saline is injected into the lesion, and a second aspirate is obtained. The two aspirates are submitted for culture and for direct staining with methenamine silver. If aspergillus is present the diagnosis can usually be obtained the same day. All of these 18 patients were treated with intravenous amphotercin B, with a cure rate of 50 per cent. In the immunosuppressed patient the spectrum of disease is a little different. The patient usually does not die of pulmonary complications, but of dissemination to other organs including the brain. In four of the patients in whom intravenous amphotericine B either failed to control the infection or resulted in significant nephrotoxicity, intralesional therapy was used. A 60-year-old man, 2 months following heart transplantation, developed an aspergilloma in his right upper lobe. The diagnosis was made in his case by a transtracheal aspirate and a lung aspirate. He was treated with intravenous amphotericin B. His kidney function deteriorated, and in addition he continued to be febrile and to produce positive sputum cultures. Accordingly, a small polyethylene catheter. was threaded into the cavity through an 18 gauge thin-wall needle. This
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The Journal of Thoracic and Cardiovascular Surgery
patient was treated for 30 days with intercavitary therapy. His fever and positive sputum cultures cleared within 5 days. He continued to do well until he died 2 years later of a bacterial pneumonia. In conclusion, I would just like to emphasize two points in the management of patients who develop suspected pulmonary aspergillosis and who are on immunosuppressive medication. First, the lung aspirate is an extremely useful, simple, and safe technique for making the diagnosis. Second, in some of these patients, infusion of chemotherapeutic agents directly into the cavity will clear the infection when systemic therapy will not. Thank you very much for the privilege of the floor and the chance to present these patients.
DR. HENDERSON (Closing) I thank Drs. Grow and Griepp for most interesting comments. We have not had experience with the management of the aspergillus empyema, and indeed, I think this is a most interesting addition to the entire discussion, and certainly the approach appears to be sensible and rewarding. The comment with regard to treatment of these patients by the intracavitary drip technique seems most sensible and perhaps applicable to some of the patients seen and discussed in this present study.
R. D. Henderson, 1. Deslaurier, E. L. Ritcey, N. C. Delarue, and F. G. Pearson, Toronto, Ontario, Canada
The fungus Aspergillus [umigatus, despite its ubiquitous nature, very rarely gives rise to human infection. The first recognized aspergillosis infection was reported by Sluyter' in 1847 and the first operative resection of an aspergilloma was carried out by Gerstl, Wideman, and Newmann- in 1948. Kilman and associates" in 1969 reviewed the world literature and reported a total of only 70 resections, adding 14 further cases of his own. This rare disease continues to present as a major therapeutic challenge. Case material Twenty-four patients have been diagnosed as having aspergillosis at the Toronto General Hospital between the years 1965 to 1975. The average age of these patients is 42 years, 15 are male and 9 female. In all cases a diagnosis was made either by sputum culture or by the recognition of Aspergillus [umigatus in a resected specimen. From the Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Read at the First Annual Meeting of The Samson Thoracic Surgical Society, Santa Barbara, Calif., May 28-30, 1975.
Address for reprints: Dr. R. D. Henderson, Rm 139, University Wing, Toronto General Hospital, Toronto, Ontario, M5G IL7, Canada.
1088
Twenty patients had cough and sputum production and in three of these the sputum production was massive. Eleven patients had hemoptysis and in four of these the hemoptysis was recurrent and massive. Other symptoms which occurred included pyrexia in four patients, weight loss in excess of 50 pounds in 4, and chest pain localized to the site of major involvement in 5 (Table I).
In those with massive sputum production the sputum had an offensive taste and odor and produced considerable distress to the patient. Although in many the hemoptysis was marked and distressing, in only four was it characterized as being massive and in these four patients bleeding episodes of several hundred cubic centimeters occurred, producing acute respiratory distress in two patients, in one a respiratory arrest requiring emergency bronchoscopy and suction, and in one a cardiac arrest. All patients had chest x-rays. In most patients tomograms were also performed and in a few more complicated radiological studies such as bronchography and pulmonary angiography were carried out. On reviewing the radiological studies 12 were considered to be nonspecific, showing diffuse lung infiltration which was not suffi-
Volume 70 Number 6
10 8 9
Pulmonary aspergillosis
December, 1975
Fig. 1. A. F., age 36, has typical radiological features. He had known tuberculosis, treated successfully 5 years previously. Hemoptysis of moderate severity had been present for 2 years. At the right apex he has a cavitary lesion with a small fungus ball. Right upper lobectomy has successfully removed his aspergilloma and stopped the hemoptysis.
ciently characteristic to allow for diagnosis. In one patient a bulla was recognized but the presence of aspergillus in this bulla was not evident. Eleven patients had a typical radiological mass with cavitation and a recognizable fungus ball and air crescent most characteristic of aspergillosis (Fig. 1). Fifteen of the 24 patients had aspergillus cultured from their sputum. Six patients had serological studies which were positive. Aspergillus is recognized as complicating pre-existing pulmonary disease, usually of a cavitary type. In the patients seen, 22 of the 24 had an underlying disease considered to be a significant etiologic factor. Eight of these had tuberculous cavities, five had bronchiectasis, two had sarcoid, and two had silicosis. Other diseases occurring in individual patients were asthma , ankylosing spondylitis, pulmonary radiation, scleroderma, and an empyema cavity secondarily infected by aspergillus. One patient was terminally ill from hepatitis and the aspergillosis was considered to be related to an altered immunological mechanism. Seventeen patients have had surgical procedures. In three a lung biopsy was obtained
Table I. Symptoms in 24 patients with pulmonary aspergillosis" Symptom
Cough and sputum Massivesputum Hemoptysis Massivehemoptysis Pain Pyrexia Weight lossgreater than 50 pounds
4
• A wide variety of symptoms were present, but cough , sputum production, and hemoptysis predominated.
for tissue diagnosis by limited thoracotomy but no attempt was made at resection. In one patient a tracheostomy was done at the time of respiratory failure which eventually proved to be terminal. Thirteen of the 24 patients have been treated by major lung resection. In these 13 patients the radiological features were classified in the manner reported by Belcher and Plummer.' with this classification aspergillosis was subdivided into allergic aspergillosis, aspergillomas, and suppurative aspergillosis. No patient with allergic aspergillosis was treated surgically. Aspergillomas were di-
1 09 0
Henderson et al.
The Journol of Thoracic and Card iovascular Surgery
Fig. 2. Patient F., age 60, presented with typical radiological changes present at both apices. On the left a large fungus ball was present in a pre-existing tuberculous cavity . A crecent of air can be seen on the upper surface of the fungus mass. This would be classified as bilateral complex aspergillomas.
vided into simple and complex, depending on their radiological appearance. The sim. pIe aspergilloma was considered to be an infection complicating a thin-walled cyst of bronchial origin in which there was little or no abnormality in the surrounding lung tissue. A complex aspergilloma was considered to develop in a pre-existing cavity produced by some form of destructive lung disease such as tuberculosis. In this case the lesion was in the cavity but the surrounding lung tissue showed evidence of established disease. According to this classification, one of the patients operated upon had a simple aspergilloma, 10 had complex aspergillomas, and two had suppurative aspergillosis. The patients operated upon were treated surgically because of severe and progressive symptomatology or because of major and rapidly progressing complications . In the one case of a simple aspergilloma surgical resection was undertaken because of the presence of the bulla and the aspergillosis was not recognized until examination of the resected specimen. This method of selection has resulted in the majority of patients
operated upon being of very high operative risk because of advanced pulmonary disease. One patient had a wedge resection of an apical aspergilloma . Eight patients were treated by lobectomy and four by pneumonectomy. In those treated by lobectomy three required thoracoplasty because of an inexpansile lower lobe. Five of the 13 patients treated surgically died of complications directly related to their disease or to the operative procedure. This very high mortality rate compares with less than 4 per cent in the same unit for lung resection in patients with bronchogenic carcinoma. Undoubtedly a contributing factor to this mortality rate is the extreme debility of many of these patients treated and the emergency nature of the surgical resection which proved necessary. In one patient pneumonectomy was performed for extensive and unilateral suppurati ve aspergillosis. This patient died on the seventh postoperative day from a major hemorrhage related to a bronchoarterial fistula. Two patients had acute respiratory failure requiring ventilatory care following masssive hemoptysis and resection was necessary because
Volume 70 Number 6 December, 1975
Fig. 3. Patient F., following resection and left thoracoplasty, developed a residual space above his inexpansible left lower lobe. Chronic tube drainage of this space gave satisfactory control of his symptoms for 2 years.
of continued bleeding. Although bleeding was controlled by surgical resection, their respiratory failure was not reversible. One patient had two massive hemoptyses followed by cardiac arrest and at the time of a third hemoptysis a lobectomy was done as an emergency procedure. He died following a massive myocardial infarct and cardiac failure 10 days following resection. The final patient who died had involvement of his aortic arch by aspergillosis and at the time of resection the aortic arch was opened and required prosthetic replacement. He had a delayed thrombosis in the graft and died following this complication. Two of the patients dying had pneumonectomies and three had been treated by lobectomy. Of the eight surviving patients three had uncomplicated lobectomies and five required extensive and difficult resection because of very dense pulmonary adherence or direct growth of the aspergilloma through and into the chest wall. A thoracoplasty was necessary in three because of poor expansion of the residual lung tissue.
Pulmonary aspergillosis
10 9 ]
Fig. 4. Patient F. developed a complex aspergillorna at the base of his right lung. This has occurred 2 years following left upper lobectomy.
Follow-up of surgical patients ranges from 2 to 48 months and averages 20 months. With one exception those patients with resected disease are progressing well and show no evidence of dissemination of their aspergillosis. One patient (Fig. 2) has a residual apical pleural space requiring long-term tube drainage (Fig. 3) . He has developed a complex aspergilloma in the right lower lobe 2 years following his initial resection and his respiratory function has further deteriorated (Fig. 4). Discussion Pulmonary aspergillosis may present clinically in a variety of ways.":' It may present as a radiological density which is nonspecific and requiring diagnosis. It may present as a complication of recognized and preexisting pulmonary disease with invasion of damaged lung tissue.H In a significant percentage of patients the presentation is one of progressive pulmonary infection or of massive hemoptysis. In this particular group of patients management is extremely difficult and if surgery is undertaken the operative mortality rate is high. Established methods of diagnosis include
The Journal of
10 9 2
Henderson et al.
Thoracic and Cardiovascular Surgery
the recognition of the pre-existing disorder and with this the realization that alteration in the radiological appearance may well be related to a secondary aspergilloma. The radiologic features are a composite picture of pre-existing lung disease and the superadded changes related directly to an aspergillus infection. The most characteristic radiological changes are those of a fungus ball with an associated crescent of air. The fungus ball by itself is not diagnostic in that this can be mimicked by necrotic tissue of any source lying within the cavity. Alternate sources of such necrotic debris include blood clot and carcinoma, or a ruptured hydatid cyst. When followed over a period of several weeks most necrotic tissue will be broken down and coughed up, giving alteration in the appearance of the central mass. This alteration is rarely seen in aspergillosis over such a short period of time." By changing the position of the patient it may be possible to show movement of the fungus ball and by this maneuver demonstrate its position within the lumen of the cavity. Sputum culture is frequently positive in that the aspergilloma being free within the cavity is communicating with the tracheobronchial tree and constantly shedding filaments of fungus. Skin tests are of little value, however, serology is diagnostically significant and should be used to confirm the presence of an aspergillus infection. o, 10 Drug therapy has not proved to be of much value but the drug of choice is amphotericin BY, 12 There is no indication that this drug has any value in the patient with a solitary fungus ball but it has been used in far-advanced and complicated fungal infections and in these situations has been reported to be of some clinical value. Surgical resection has been reserved mostly for progressive aspergillosis and for those in whom the complications of the disorder are life threatening."?" With this method of selection in the 13 patients treated with major pulmonary resections many of those treated surgically were found to have extremely advanced disease and indeed many had reached the stage where surgery
was the only hope of controlling their complications. Under these circumstances the surgical mortality rate has proved to be extremely high. In other reported series the mortality rate is considerably lower; however, this would appear to be related to the severity of the pre-existing disorder at the time of resection. REFERENCES Sluyter, T.: De Vegetalibus Organisrni Animalis Parasitis, Diss. Maug. Berolini, p. 14, 1847 (cited by Renon, 1897). 2 Gerst!, B., Wideman, W. H., and Newmann, A Y.: Pulmonary Aspergillosis: Report of 2 Cases, Ann. Int. Med. 28: 662, 1948. 3 Kilman, J. W., Changoo, A, Andrews, M. D., and Klasser, K.: Surgery for Pulmonary Aspergillosis, J. THORAc. CARDIOVASC. SURG. 57: 642, 1969. 4 Belcher, 1. R., and Plummer, N. S.: Surgery in Broncho-pulmonary Aspergillosis, Br. J. Dis. Chest 54: 335, 1960. 5 Pesle, G. D., and Monod, 0.: Bronchiectasis Due to an Aspergilloma, Dis. Chest 25: 172, 1954. 6 Saliba, A, Pagnini, L., and Beatty, O. A: Intracavity Fungus Balls in Pulmonary Aspergillosis, Br. J. Dis. Chest 55: 65, 1961. 7 Bruce, R. A: Case of Pulmonary Aspergillosis, Tubercle 38: 203, 1960. 8 Irwin, A.: Radiology of the Aspergilloma, Clin. Radiol. 18: 432, 1966. 9 Henderson, A H., English, M. P., and Yecht, R. J.: Pulmonary Aspergillosis. A Survey of Its Occurrence in Patients With Chronic Lung Disease and a Discussion of the Significance of Diagnostic Tests, Thorax 23: 513, 1968. 10 Longbottom, 1. L., and Pepys, J.: Pulmonary Aspergillosis: Diagnostic and Immunological Significance of Antigens and C-Substance in Aspergillus [umigatus, 1. Pathol. Bacteriol. 88: 141, 1964. 11 American Thoracic Society Committee of Therapy: Am. Rev. Resp. Dis. 86: 784, 1967. 12 Peer, E. T.: Case of Aspergillosis Treated With Amphotericin B, Dis. Chest 38: 222, 1960. 13 Schwartz, J., Baum, G. L., and Straub, M.: Cavitary Histoplasmosis Complicated by Fungus Ball, Am. J. Med. 31: 692, 1961. 14 Davies, D.: Pulmonary Aspergillosis, Can. Med. Assoc. J. 89: 392, 1963. 15 Foushee, J. H. S., and Norris, F. G.: Pulmonary Aspergillosis, J. Thorac. Surg. 35: 542, 1958. 16 Peccra, D. Y., and Toll, M. W.: Pulmonary Resection for Localised Aspergillosis, N. Eng!. J. Mee!. 263: 785, 1960.
Volume 70
Pulmonary aspergillosis
Number 6 December, 1975
Discussion DR. JOHN B. GROW, SR. Denver, Colo.
I think that it is very appropriate that we should have a paper like this in a meeting that is so heavily weighted in cardiac surgery. As Dr. Lawrence said this morning, most of us spend our time sewing veins to various structures and pay little attention to the chronic infections of the chest which we used to see so much. When I was told that I could discuss this paper, I hurriedly looked through our cases to see how many cases we have had, and in 40 years I have seen eight patients operated upon. So it is not just something you see every day. I think that this shows us what we learned from the surgical treatment of tuberculosis a good many years ago, and that is that if you cannot control the organism, your surgical results are going to be poor. Before the advent of streptomycin, ionase, and the other drugs, we did a very good job of our surgery in tuberculosis, particularly resection. I think in a way this is analogous. Since the results of amphotericin B are at best unreliable, and we do not have any other drug that will really be effective in this disease, we can anticipate poor results following resection. One of the other problems we have is that our diagnostic facilities are not the best. We depend on sputum culture. Actually, tissue examination is the most reliable means of examining the lung, and we do not really find that out until surgery. So that if we did not want to use prophylactic amphotericin B, most of the time we would end up not making the diagnosis until the chest is open. Of our eight patients, all survived, but two had empyema. I thought that perhaps I might address the problem of what to do with empyema since these two empyemas were something of a problem. Those of you who have seen empyema following aspergillus infections know what I am talking about. You look inside the pleural space, and there is a thick coating of white substance that looks like coating on a cake, and when you lift this off, it leaves an inflamed bleeding surface. These things just do not heal, and so if you have such a problem, you have to make up your mind what you are going to do about it. The way we decide to treat it was by giving intravenous amphotericin B and peeling this peel off and then spraying the inside of the cavity with an amphotericin B solution. In both instances, the white peel did eventually disappear after IO days to 2 weeks, and we were able to go ahead with thoracoplasty and obliterate the space.
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I think when such complication occurs, that you do have to go ahead and realize that the chance of the thing healing as empyema would heal is almost nil. DR. RANDALL B. GRIEPP Stanford, Calif.
I enjoyed this paper very much, and I rise to mention another group of patients in whom aspergillus can be a problem. This is the increasingly large number of patients that have been treated with toxic drugs for cancer chemotherapy or for organ allograft rejection. Pulmonary aspergillosis is becoming an increasingly difficult diagnostic and therapeutic problem in these patients. I would like to mention 18 cases of premortemdiagnosed pulmonary aspergillosis that we have encountered in the past 7 years in a total of 84 heart transplants. In all of these patients, owing to their compromised immunocompetence and poor tissue healing, we did not want to proceed with diagnostic or therapeutic modalities that involved thoracotomy. As a consequence, we relied heavily on the routine sputum culture, the transtracheal aspirate, and the direct lung aspirate. I would like to discuss this latter technique in a little more detail. In 14 of these 18 cases, direct lung aspirates were carried out and positive diagnoses were obtained in all 14. Aspiration of pulmonary nodules is a relatively simple procedure involving passing an 18 gauge thin-wall needle directly into the lesion under fluoroscopic control. A sample is aspirated from the lesion, some preservative free saline is injected into the lesion, and a second aspirate is obtained. The two aspirates are submitted for culture and for direct staining with methenamine silver. If aspergillus is present the diagnosis can usually be obtained the same day. All of these 18 patients were treated with intravenous amphotercin B, with a cure rate of 50 per cent. In the immunosuppressed patient the spectrum of disease is a little different. The patient usually does not die of pulmonary complications, but of dissemination to other organs including the brain. In four of the patients in whom intravenous amphotericine B either failed to control the infection or resulted in significant nephrotoxicity, intralesional therapy was used. A 60-year-old man, 2 months following heart transplantation, developed an aspergilloma in his right upper lobe. The diagnosis was made in his case by a transtracheal aspirate and a lung aspirate. He was treated with intravenous amphotericin B. His kidney function deteriorated, and in addition he continued to be febrile and to produce positive sputum cultures. Accordingly, a small polyethylene catheter. was threaded into the cavity through an 18 gauge thin-wall needle. This
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patient was treated for 30 days with intercavitary therapy. His fever and positive sputum cultures cleared within 5 days. He continued to do well until he died 2 years later of a bacterial pneumonia. In conclusion, I would just like to emphasize two points in the management of patients who develop suspected pulmonary aspergillosis and who are on immunosuppressive medication. First, the lung aspirate is an extremely useful, simple, and safe technique for making the diagnosis. Second, in some of these patients, infusion of chemotherapeutic agents directly into the cavity will clear the infection when systemic therapy will not. Thank you very much for the privilege of the floor and the chance to present these patients.
DR. HENDERSON (Closing) I thank Drs. Grow and Griepp for most interesting comments. We have not had experience with the management of the aspergillus empyema, and indeed, I think this is a most interesting addition to the entire discussion, and certainly the approach appears to be sensible and rewarding. The comment with regard to treatment of these patients by the intracavitary drip technique seems most sensible and perhaps applicable to some of the patients seen and discussed in this present study.