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Ann Thorac Surg 1998;66:325-330
© 1998 The Society of Thoracic Surgeons

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Original articles: general thoracic

Results of operation in Mycobacterium avium-intracellulare lung disease

^a Department of Surgery, The University of Texas Health Center, Tyler, Texas, USA
^b Department of Microbiology, The University of Texas Health Center, Tyler, Texas, USA
^c The Center for Pulmonary Infectious Disease Control, The University of Texas Health Center, Tyler, Texas, USA

Address reprint requests to Dr Nelson, The University of Texas Health Center, PO Box 2003, Tyler, TX 75710

Presented at the Forty-fourth Annual Meeting of the Southern Thoracic Surgical Association, Naples, FL, Nov 6–8, 1997.

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. Although operation remains part of the management of Mycobacterium avium-intracellulare lung disease, few series have assessed operation in the era of better therapeutic drugs (especially clarithromycin).

Methods. From January 1, 1989, through June 30, 1997, 28 patients with M avium-intracellulare lung disease underwent pulmonary resection. All were receiving multidrug therapy (17 of 28 were receiving clarithromycin) before and after operation. Eight patients underwent pneumonectomy (6 right, 2 left); 20 patients underwent partial resections including 18 with upper lobe lobectomies (14 right, 4 left). The most common indications for operation were medical treatment failure (15) and as part of initial therapy (9).

Results. Mean postoperative follow-up was 39 months. Complications occurred in 9 of 28 patients (32%), and included persistent air leak requiring surgical correction (5), early postoperative death (2), and late bronchopleural fistulae (1 patient). Twenty-three of 26 patients were known to be acid fast bacilli culture negative within 1 month of operation. Only 1 of 26 patients who survived 2 years is known to have had a relapse.

Conclusions. Operation continues to play an important role in treatment of M avium-intracellulare lung disease. More than 90% of patients become culture negative and remain so when they continue to receive drugs. Although morbidity is relatively high, it is manageable and the 12-month mortality in the current series was low (7%).

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Pulmonary disease due to the nontuberculous mycobacteria (NTM) shows a variable pattern, both in its geographic distribution and in the type of clinical disease. Although disease due to Mycobacterium kansasii is the most common NTM disease in the central United States, disease due to M avium and M intracellulare (generally referred to as the M avium complex or MAC) is the most common NTM infection in the southern and southeastern United States including Texas. Although disease due to MAC and other NTM is not reportable so disease incidences are unknown, MAC isolates are being encountered with increasing frequency in the laboratory. The Centers for Disease Control and Prevention evaluated more than 13,000 mycobacterial isolates collected and identified in 38 state public health laboratories in 1991 and 1992, and found that MAC had become the most common mycobacterial species, being more common than even M tuberculosis (34% versus 26% of the total isolates) [1]. Some of this increase reflects the human immunodeficiency virus epidemic, but many experts believe this also reflects an increase in the prevalence or recognition of MAC lung disease.

Despite the introduction of newer effective agents for the treatment of MAC such as clarithromycin [2–4] and rifabutin [3, 4], response to drug therapy in MAC disease remains difficult and often frustrating, and operation is still recognized as playing a significant role in the care and management of these patients [5].

The surgical experience with NTM lung disease at The University of Texas Health Center at Tyler has involved patients with MAC lung disease in almost 90% of cases. This report presents our surgical experience with MAC during the past 8.5 years.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Surgical records of The University of Texas Health Center were screened retrospectively for all patients who had undergone thoracic operation for MAC disease between January 1, 1989, and June 30, 1997. Clinical and microbiological records on the identified patients were then reviewed. Patients were included if they had undergone thoracic operation for MAC lung disease, had multiple positive sputa for MAC, and met the recent American Thoracic Society criteria for lung disease due to the NTM [6].

Respiratory samples submitted to the microbiology laboratory were concentrated and decontaminated using standard methods [7]. They were screened for the presence of acid-fast bacilli using a fluorochrome method, with semiquantitative grading of 0 to 4+. Samples were cultured on Middlebrook 7H10 agar, also with semiquantitative grading of 0 to 4+ for growth. Samples were also plated on Löwenstein-Jensen agar, and in the BACTEC system (Becton Dickinson, Towson, MD). Cultures were considered positive if they grew on any of these media. Organisms were identified as MAC by standard methods [7], including the use of DNA probes (Accuprobe; GenProbe, Inc, San Diego, CA).

Susceptibility testing to clarithromycin was performed on MAC isolates from patients on therapy with clarithromycin using a broth microdilution method as previously described [8].

Microbiologic relapse was defined as two or more positive cultures with one or more being acid-fast bacilli smear positive, or three or more positive cultures, which are all acid-fast bacilli smear negative [6] after being culture negative a minimum of 4 months.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Patients
Between January 1, 1989, and June 30, 1997, 28 patients with MAC lung disease underwent a thoracic operation. None of these patients were known to be or suspected of being positive for human immunodeficiency virus. These patients were part of more than 300 patients with proven or suspected MAC disease seen or evaluated by the medical service during this time period. Many were enrolled in multidrug treatment trials approved by the Institutional Human Subjects Investigational Committee that began with the Food and Drug Administration approval of clarithromycin and rifabutin in the early 1900s [3].

Surgical patients ranged in age from 29 to 75 years, with a median age of 48 and a mean age of 50.3 ± 11.3 years (standard deviation). The majority of the patients were men and white (both 21 of 28 or 75%). Almost all were current heavy smokers, and some had a history of alcohol abuse. All had multiple positive cultures for MAC within 1 year of the date of operation. All had cavitary disease on chest roentgenogram.

All patients were symptomatic, with some combination of fever, weight loss, malaise, fatigue, cough, sputum production, and hemoptysis being present before operation. In 2 patients, cough was so severe and persistent as to interfere with nutrition. These 2 patients weighed 81 and 87 pounds, respectively. Both required gastrostomy for nutritional support.

The nutritional status in all the patients was generally poor. Of the 28 patients, 19 were 20% or more below the American Dietetic Association Standards for height and weight [9]. Three were 40% or more below the standards. Factors contributing to early weight loss and malnutrition included both MAC disease as well as the multidrug therapy. All of the drugs used are a potential cause of gastrointestinal symptoms, including nausea, vomiting, diarrhea, and anorexia.

Drug therapy
Drug therapy generally consisted of three or more drugs. Therapy depended on when the patient was treated in time. Between 1989 and 1991, patients received isoniazid, rifampin, ethambutol, and usually initial streptomycin. With the introduction of clarithromycin and rifabutin, patients seen after 1991 received these two agents in combination with ethambutol and often initial streptomycin. Most patients in the latter group were in drug treatment trials [3, 6]. Other companion drugs included rifampin, ofloxacin, ciprofloxacin, and amikacin.

These drugs were used generally 1 to 2 years before operation, occasionally up to 6 years. The treatment philosophy, especially in the era of the macrolides, was to treat patients with drugs (even when they appeared to be cured by operation) until culture-negative at 12 months [3, 6].

Indications for operation
All patients had cavitary disease with destroyed lung. The primary indications for operation were related to efforts to cure the disease, and appeared different depending on the treatment era in which they occurred. Of the 11 patients with surgical resection in the premacrolide era, 8 were operated on as part of their initial therapy to facilitate cure of their infection. In contrast, the major indication for surgical resection used in the macrolide era was drug treatment failure with or without macrolide resistance (12 of 17 or 71%) (Table 1). A small number of patients were operated on because of complications of their destroyed lung, specifically massive hemoptysis or severe symptomatic bronchiectasis.

Bronchial stumps require special consideration in pneumonectomies [5, 7, 9]. If dissection has been carried out in an intrapleural plane, then a local pleural flap is preferred for stump reinforcement. Even when the plane is extrapleural on the left, there is usually sufficient local tissue for reinforcement; however, on the right this is usually not possible. For those patients who undergo a right pneumonectomy, an extrathoracic muscle is needed to minimize the risk of a bronchopleural fistula. This can be most easily accomplished by making the thoracotomy incision somewhat low and then preserving the entire serratus anterior by mobilizing it off ribs 8 to 5. The muscle is dropped in through a segmental resection of its third rib anterolaterally. This will easily reach the bronchial stump and still preserve the function of the upper serratus with mild to no winging. The muscle is sewn circumferentially around the bronchial stump with 4-0 Prolene (Ethicon, Somerville, NJ) suture. This can also be done with an anterior thoracotomy incision by initially splitting the anterior fibers of the serratus over the third or fourth rib while preserving the neurovascular bundle. In this case the muscle may be used to cover the raw surface of the middle lobe after right upper lobectomy. One problem with this technique is that in creating an entrance for the muscle, you also create an exit for postoperative fluid to run into the subcutaneous tissues creating a seroma (a problem noted with 1 patient in the current series). Shoulder physical therapy is not encouraged for 5 days before gradual motion is started to try to minimize this risk.

Apical dissection can be hazardous and a decision may have to be made to abandon an extrapleural dissection and to cross the cavity. Often this situation occurs spontaneously during dissection, as the fibrotic process will often obliterate all landmarks at the apex. At this point cultures are taken and the cavity is crossed, removing all spilled material, curretting the cavity wall if necessary, and continuing the dissection to the hilum.

Staples have limited use on lung tissue. They frequently compromise lung expansion, which is already restricted in the remaining lung due to the long-standing fibrosis or granulomatous disease.

Once the lung is removed, bronchial cultures, as well as tissue cultures, are obtained for acid-fast bacilli, fungus, aerobes, and anaerobes.

At this point it is necessary to evaluate the expansion of the residual lung to fill the pleural space. At the same time, alveolar air leaks must be evaluated. Pleural tent is rarely useful or available as there is often insufficient pleura remaining. In addition, pneumoperitoneum offers little benefit. Occasionally it will move the lung up, but it interferes with the function of the opposite lung and also interferes with gastric filling and nutrition. Thus, either a muscle flap at the time of operation or the use of a limited thoracoplasty, either at the time of operation or later is used.

We have tended to do the latter, 1 to 3 weeks after lobectomy, hoping to get maximum expansion of the lung and to determine whether air leaks will seal and thus avoid a second procedure. Fifty percent of air leaks close within 7 days, another 25% close within 14 days. The remaining 25% require a second procedure. Persistent air leak is usually related to granulomatous disease in the residual lobes where there is sufficient good lung tissue to merit preservation rather than perform a pneumonectomy. A space without an air leak does not present a problem and will gradually resolve. A space with an air leak needs further management in the form of a muscle flap or thoracoplasty. Thoracoplasty is done by taking ribs above the line of lung expansion (usually ribs 2, 3, and 4) and resecting to the transverse process posteriorly. The first rib may not be taken but the underside is cleared allowing the fascia to drop away. More recently a muscle flap is transposed, usually the serratus anterior. Latissimus dorsi may also be used [5].

Blood loss
Estimated blood loss was primarily related to the need for an extrapleural resection whether the patient underwent lobectomy or extrapleural pneumonectomy. Blood loss in extrapleural pneumonectomy and completion pneumonectomy ranged from 1,600 to 3,500 mL, with an average of 2,500 mL. Blood loss in lobectomies and segmental resections was less than 500 mL in 7 patients, 500 to 1,000 mL in 7 patients, and more than 1,000 mL in 5 patients, with the highest being 4,400 mL.

Follow-up and eradication of disease
Almost 50% of patients (13 of 27) with known bacteriology were culture negative before operation (Table 4), and another 8 patients had low colony counts (efforts were made to make patients as culture negative as possible before undergoing operation). Twenty-two of 24 patients (93%) alive with cultural follow-up were culture negative within 3 months of operation. All but 1 of these was culture negative within 1 month. Two of 24 patients (7%) remained culture positive more than 4 months after operation.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
Operation continues to play an important role in the management of fibrocavitary M avium-intracellulare lung disease even with the development of newer, better drugs such as clarithromycin. Currently it appears that better than 90% of patients who undergo resection can achieve permanent control of their disease. Timing of surgical intervention is still problematic, and no real recommendations for who to operate on and when have been set forth for this disease.

The use of muscle flaps are important adjuncts for this type of operation, especially with a right pneumonectomy to minimize the risk of a late bronchopleural fistula. Such muscle flaps were not used routinely in the current series with a relatively low risk of bronchopleural fistulae (1 of 6 patients or 17%), but should be considered if an adequate pleural flap is not available. In the series by Pomerantz and colleagues [5] it should be noted that bronchopleural fistulas were still a problem despite the use of this procedure. Muscle flaps were not used in this series for patients who underwent lobectomy, but has been recommended by others for patients with positive acid-fast bacilli cultures at the time of operation or individuals considered high risk for a residual space problem to minimize this risk [5, 10]. Bronchopleural fistulas remain the major complication associated with long-term morbidity and mortality with operation for MAC disease [5, 10, 11].

In our experience, M avium-intracellulare fibrocavitary disease is more common in white men and occurs predominantly in the right lung, a finding previously noted by other investigators [5, 10]. Although morbidity was relatively high, the postoperative complications are generally manageable and the 2-year mortality in the current series of 28 patients was only 7%.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Ostroff S, Hutwagner L, Collin S. Mycobacterial species and drug resistance patterns reported by state laboratories—1992. Abtract U-9. American Society for Microbiology 93rd General Meeting, Atlanta, GA, 1993:170.
2. Chaisson R.E., Benson C.A., Dube M.P., et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. Ann Intern Med 1994;121:905-911.[Abstract/Free Full Text]
3. Wallace R.J., Jr, Brown B.A., Griffith D.E., et al. Clarithromycin regimens for pulmonary Mycobacterium avium complex. Am J Respir Crit Care Med 1996;153:1766-1772.[Abstract]
4. Shafran S.D., Singer J., Zarowny D.P., et al. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med 1996;335:377-383.[Abstract/Free Full Text]
5. Pomerantz M., Madsen L., Goble M., Iseman M. Surgical management of resistant mycobacterial tuberculosis and other mycobacterial pulmonary infections. Ann Thorac Surg 1991;52:1108-1112.[Abstract]
6. Wallace R.J., Jr, Cook J.L., Glassroth J., et al. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med 1997;156:S1-S25.
7. Nolte F.S., Metchock B. Mycobacterium. In: Murray P.R., Baron E.J., Pfaller M.A., Tenover F.C., Yolken R.H., eds. Manual of clinical microbiology. Washington DC: American Society for Microbiology, 1995:400-437.
8. Brown B.A., Wallace R.J., Jr, Onyi G.O. Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system. Antimicrob Agents Chemother 1992;36:1987-1990.[Abstract/Free Full Text]
9. Miller M.A. A calculated method for determination of ideal body weight. Manual of clinical dietetics. Chicago: The American Dietetic Association, 1988:31-33.
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11. Hattler B.G., Young W.G., Sealy W.C., Gentry W.H., Cox C.B. Surgical management of pulmonary tuberculosis due to atypical mycobacteria. J Thorac Cardiovasc Surg 1970;59:366-371.[Medline]

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