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Ann Thorac Surg 2001;72:889-893
© 2001 The Society of Thoracic Surgeons

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Original article: general thoracic

Surgical outcome of pulmonary resection in chronic necrotizing pulmonary aspergillosis

^a Department of Thoracic Surgery, Jichi Medical School, Tochigi, Japan

Accepted for publication May 16, 2001.

Address reprint requests to Dr Endo, Department of Thoracic Surgery, Jichi Medical School, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan
e-mail: tcvshun{at}jichi.ac.jp

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Surgical treatment of chronic necrotizing pulmonary aspergillosis is hazardous and controversial.

Methods. Ten patients (8 men, 2 women; mean age, 50 years) with chronic necrotizing pulmonary aspergillosis underwent pulmonary resection between 1989 and 2000. Single segmentectomy or lobectomy, pneumonectomy, or bilobectomy and multisegmentectomy were performed. Clinicopathologic features of these patients were reviewed to clarify the role of surgical intervention for chronic necrotizing pulmonary aspergillosis.

Results. The mean time from the onset of clinical symptoms to operation was 5.3 years. Surgical intervention was undertaken because of prolonged illness in 4 patients and hemoptysis in 6 patients. All patients survived. Three major complications (1 late empyema, 2 bronchopleural fistulas) occurred in the large dead space in the right pleural cavity. All survivors were free of aspergillosis at a mean follow-up time of 4.8 years, and only 1 patient required antifungal drugs for relapse during the follow-up period.

Conclusions. Aggressive pulmonary resection in chronic necrotizing pulmonary aspergillosis should be considered when patients have prolonged illness or frequent hemoptysis. Empyema and bronchopleural fistula are the main complications. Concomitant thoracoplasty or intrathoracic transposition of the chest wall musculature is recommended in cases involving a large residual pleural cavity on the right side.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
A variety of clinical entities resulting from the allergic, saprophytic, and invasive types of aspergillosis have been described [1, 2]. The clinical and pathologic manifestations of Aspergillus infection depend on the underlying lung architecture, the host immune response, and the degree of inoculum [3]. In the saprophytic form of the disease, aspergillomas establish themselves in preexisting cavities. Consequently, it is believed that the fungus tends to first develop innocuously within these cavities. The chronic cavitary form of aspergillosis, which produces a slowly progressive infiltrate that may include mycetoma, was proposed in 1981 as a new category of semiinvasive pulmonary [4] or chronic necrotizing pulmonary aspergillosis (CNPA) [5]. The decision to institute therapy in such patients is a difficult one due to the hazards of operation and antimycotic chemotherapy. During the past 10 years, we have performed pulmonary resections in 10 patients with CNPA. We attempted to clarify the role of such surgical intervention by conducting a retrospective analysis of clinicopathologic features of these 10 patients.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
We identified 10 cases of CNPA among 33 patients with pulmonary aspergillosis who received surgical treatment between 1989 and 2000. The 23 patients excluded from this study showed saprophytic growth in preexisting cavities. Patients included in the study were selected on the basis of the following criteria [4, 5].

1. Radiographic documentation of a chronic and progressive cavitary process with or without mycetoma, and that resulted from Aspergillus invasion to lung tissue that began more than 30 days before the start of treatment.
   
2. Clinical, radiographic, and pathologic data failing to show an etiology for the pulmonary cavities other than that of Aspergillus infection.
   
3. Antifungal therapy that was ineffective or was discontinued because of its toxicity.
   

Patient characteristics
Preoperative clinical characteristics of the 10 study patients are summarized in Table 1. The study group consisted of 8 men and 2 women. Mean age at the time of operation was 50 years (range, 33 to 67 years). Bullous emphysema (n = 5), old tuberculosis (n = 3), pneumonitis complicated by rheumatoid arthritis (n = 1), and allergic bronchopulmonary aspergillosis (n = 1) were evident. Four patients were treated previously by pulmonary resection. Procedures included bullectomy for pneumothorax (n = 3) and right lower lobectomy for tuberculosis (n = 1). One subject had received recent steroid treatment for allergic bronchopulmonary aspergillosis. Symptoms attributable to bronchitis, such as cough, sputum, and fever, were noted in all patients. Frequent hemosputum was noted in 6 patients. The average respiratory function during the most recent preoperative period was 1,633 ± 429 mL of forced vital capacity per body surface area and 1,355 ± 348 mL of forced expiratory volume at 1.0 second per body surface area.

View larger version (83K): [in this window] [in a new window]   Fig 1. Chest computed radiographs (A, patient 2; B, patient 3) showing progressive fibrous deterioration surrounding the expanding cavities and dilating bronchus with marked pleural thickening.

Surgical intervention
Segments or lobes containing fibrous lesions around the cavities were resected. The bronchial stump was sutured by applying cartilage longitudinally onto the mucosa (ie, by Sweet’s technique [6]) with interrupted suturing and nonabsorbable thread.

Operation was performed on the right side in 6 patients, on the left side in 3 patients, and bilaterally in 1 patient. Eleven operations, including two-stage procedures for bilateral pulmonary resections were performed. Single segmentectomy or lobectomy were performed in 3 patients, and 7 patients underwent either multiple segmentectomy, bilobectomy, or pneumonectomy. Concomitant extrapleural resection was necessary in 9 patients, and 2 of them required additional chest wall resection for severe adhesion. Surgical procedures and focal lesions are summarized in Table 2.

Analysis
In these patients with CNPA, we reviewed the usefulness of antifungal therapy and embolization treatment, the indications for operation, the pathologic findings, operative morbidity and mortality, and outcomes.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Preoperative clinical course and indications for operation
The preoperative clinical courses are summarized in Table 1. The mean duration of antifungal medication treatment was 4.7 ± 2.5 months (range, 2 to 10 months). Response to chemotherapy, including reduced inflammation, sero-negative change, or radiologic reduction of fungal lesions, was observed in 6 patients (response rate, 67%). Recurrence was seen in 2 patients. Renal side effects led to the discontinuation of therapy in 1 patient. Prolonged illness in 4 patients necessitated surgical intervention. The remaining 6 patients had hemoptysis and underwent operation after embolization failure due to circulatory supply from multiple arterial branches. Two of these patients needed immediate operation because of massive airway bleeding. The mean time from onset of symptoms to operation was 5.3 years (range, 0.5 to 12 years), and the mean cumulative hospitalization stay was 98 days (range, 0 to 415 days).

Operation, postoperative complications, and hospital course
Operation time ranged from 225 to 650 minutes (mean, 393 ± 130 minutes). Mean intraoperative blood loss was 1,990 ± 1,099 mL (range, 540 to 3,700 mL). Blood transfusion was necessary in 9 patients.

The postoperative clinical courses are summarized in Table 2. In 1 patient, intrapleural hemorrhage necessitated chest wall resection to control bleeding 1 day after the resection. Bronchopleural fistula occurred in 2 patients, and late empyema at 6 months after operation was observed in 1 patient. Large dead spaces were observed in the right pleural cavity, after upper and middle lobectomy with S6 segmentectomy in 2 patients and after completion pneumonectomy in 1 patient. Open window thoracotomy followed by thoracoplasty was performed in all patients, with 2 patients undergoing omentopexy on the bronchopleural fistula. Postoperative hospital stay ranged from 13 to 233 days (mean, 86.3 ± 76 days). Excluding the cases complicated by empyema and bronchopleural fistula (n = 3) and two-stage bilateral pulmonary resection (n = 1), hospital stay ranged from 13 to 45 days (mean, 34.3 ± 11.6 days).

Pathologic findings
A solitary lesion occurred in the upper lobe in 4 patients and at the basal segment in 1 patient. Multiple focal lesions throughout at least one lobe were identified in 5 patients. The maximum diameter of the cavities ranged from 1.5 to 9.5 cm (mean, 4.1 ± 2.5 cm). Six patients showed mycetoma formation. All specimens demonstrated severe fibrous degeneration displacing normal lung parenchyma surrounding the cavities or dilated bronchus containing the fungus.

Outcome
Follow-up ranged from 0.5 to 9.5 years (mean, 4.8 ± 3.1 years). Postoperative administration of itraconazole was required for 6 months in 3 patients. It was discontinued within month after operation in the remaining 6 patients. Nine patients, including one who died as a result of cerebral infarction 9.5 years after the operation, displayed no signs of recurrence after cessation of the antifungal therapy. One patient received antifungal chemotherapy for recurrent pulmonary aspergillosis at 3 years after operation. The average respiratory function during the postoperative period was 1,238 ± 262 mL of forced vital capacity per body surface area and 950 ± 164 mL of forced expiratory volume at 1.0 second per body surface area. Eight patients are well without oxygen support or antifungal therapy.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Aspergillus infection of the lung manifests in a wide spectrum of conditions ranging from saprophytic colonization to hypersensitivity reactions to necrotizing pneumonia with angioinvasion. Since its introduction as a new aspergillosis category, CNPA has been described in several reports [3–5, 7–10]. The histologic appearances have been detailed [11], but CNPA remains undefined as a clinicopathologic entity. Numerous patients with CNPA display underlying pulmonary conditions such as chronic obstructive pulmonary diseases, pneumonitis, and previous pulmonary resections that may predispose to changes in the local immune system [10]. Patients also exhibit complications under compromised host conditions such as steroid therapy, diabetes mellitus, and collagen disease [10]. Patients displaying severe immunocompromise, as with hematologic malignancy, renal transplantation, or recent intensive immunosuppressive chemotherapy, are clearly predisposed to invasive infection [12–14]. To clarify the clinicopathologic features and the role of surgical intervention for CNPA, such patients were excluded from this study.

Lung conditions affecting the pulmonary defense system, such as previous surgical resection, ionizing radiation therapy, or chronic obstructive lung disease, allow Aspergillus to penetrate the lung through enzyme secretion despite the absence of cavity [14]. Aspergillus has a propensity to invade pulmonary blood vessels, resulting in pulmonary infarction and subsequent necrotic cavity development and bronchus dilatation [3]. Allergic reaction to necrotizing pneumonia may contribute to promote the disease [11]. Slowly progressive fibrous deterioration observed radiographically characterized by necrotic cavity formation or infiltration of the underlying lung parenchyma develops with a marked pleural fibrotic reaction, as shown in our patient group.

The management of CNPA is not yet established. A majority of patients in our study suffered from chronic bronchitis for an extended period. Progressive but slow lesioning leads to delayed diagnosis [11]. Positive bronchial lavage culture and serologic findings may suggest the spread of invasive aspergillosis to the surrounding parenchyma. Antifungal chemotherapy is typically implemented, as in 9 of our patients. Several studies note acceptable responses with the use of amphotericin B [15–17] and itraconazole [18–20]. Response rates, particularly those of intracavitary amphotericin B and itraconazol, are excellent. The average follow-up period ranged from 1 to 2 years in the reports noted above; however, the average preoperative period of 5.3 years from the present study suggests that this 1- to 2-year period is inadequate to confirm complete resolution. Lesions may progress after prolonged disease, and Aspergillus may be only partially eradicated, as we discovered in the patients showing preoperative improvement with antifungal therapy. Most patients are unable to tolerate full therapeutic doses due to the toxic effects. Consequently, antifungal therapies may be effective only when used in a suppressive role for patients with limited life expectancy [19].

Some individuals become feeble as a consequence of prolonged illness or develop lethal hemoptysis in the course of multiple hospitalizations. The present study showed embolization to be ineffective or that it progressed to airway bleeding due to the existence of multiple feeder arteries from the chest wall [21].

The limitations of chemotherapy and embolization may necessitate surgical intervention, and saprophytic infection leaves little room for alternative therapies. With CNPA, it is important to perform a resection of sufficient width, extending to the surrounding lung parenchyma and chest wall [22]. High operative morbidity and mortality rates due to respiratory failure and to pleural space complications and bronchial aspergillosis [23] resulting in empyema and bronchopleural fistula need to be overcome [22, 24–26]. Therefore, this study was designed to establish the indications and timing for surgical intervention and to deal with postoperative complications in the treatment of CNPA. We found neither operative death nor respiratory failure; however, the high morbidity rate of 40% was identical to that obtained in earlier studies [10, 21, 22, 25].

The most common complication was bleeding. The vascular supply from the chest wall and the bronchial artery are too complex to control operatively, as demonstrated by the fact that 9 of our patients (90%) required blood transfusion [21]. Additional chest wall resection is sometimes necessary to control wall bleeding. This procedure was necessary in 1 patient who had a postoperative pleural hemorrhage.

Other complications include empyema and bronchopleural fistula associated with a large dead space of the right pleural cavity after extrapleural bilobectomy and pneumonectomy. These complications may be prevented by the intrathoracic transposition of the chest wall musculature [27, 28]. These complications can be managed successfully after open window thoracotomy followed by thoracoplasty with or without omentopexy [21, 22]. Concomitant chest wall muscle transposition and thoracoplasty may circumvent postoperative complications and reduce hospital stays, particularly in cases involving contamination of a large cavity.

Respiratory failure is an inevitable complication. Predictive evaluation of respiratory function based on lung perfusion scintigraphy is necessary after pulmonary resection because of the damage to the underlying pulmonary architecture [29].

Major surgical procedures require sufficient nutritional and performance status. In patients who undergo operation for lung cancer, poor nutritional status is a main contributor to postoperative complication [30]. Preoperative antifungal therapy should be implemented to resolve weakness caused by chronic infection.

The clinicopathology develops slowly but progressively; the critical condition is not reached quickly. Surgical intervention is likely to be effective in cases of CNPA when the following criteria are satisfied: (1) cavitary formation is progressive and airway bleeding is frequent; (2) aggressive antifungal medical therapy has failed; (3) predictive residual respiratory function is acceptable; (4) chronic infection is mild; and (5) systemic immunocompromise is not seen.

We conclude that aggressive pulmonary resection can provide effective long-term palliation in critically ill patients with CNPA. Operative morbidity can be prevented in patients by concomitant thoracoplasty or intrathoracic transposition of the chest wall musculature.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

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