Surgical Management of NTM Diseases

Abstract

Prior to the discovery of antimicrobial medications, treatment of mycobacterial disease was primarily supportive. The development of many thoracic surgical techniques was in large part due to attempts to treat tuberculosis and its complications. While antibiotic therapy is the mainstay treatment for nontuberculous mycobacterial (NTM) infections today, cure rates with medication alone remain low. In experienced centers, a multidisciplinary approach employing antibiotic therapy and surgical resection has been shown to be effective in eradicating NTM infections in highly selected patients. This chapter will present proposed indications for surgical intervention in patients with NTM disease, the recommended preoperative evaluation of potential surgical patients, surgical techniques, post-op management, and management of postsurgical complications. Additionally, surgical management for extrapulmonary infections is discussed.

History of Thoracic Surgery and Tuberculosis

Hippocrates of ancient Greece is credited with the first reference describing a thoracic surgical procedure [1]. He described treatment of “empyema” first with herbal remedies and chest physical therapy and if unsuccessful then open surgical evacuation of the empyema. For centuries, thoracic surgery was limited to surgical drainage of the chest cavity. Many patients died due to the open pneumothorax that was created to allow drainage of blood or infection. Early thoracic surgeons persisted and developed means to apply suction to drains which could then evacuate air from the chest cavity and re-expand a collapsed lung. These early techniques were mainly employed for treatment of traumatic injuries sustained in battle or complications due to infections. In the early 1900s, Mycobacterium tuberculosis was a leading cause of death. With no effective antimicrobial agents, and the knowledge that M. tuberculosis was an obligate aerobe, thoracic surgeons began to develop procedures that were intended to treat mycobacterial infections. A range of surgical techniques were developed including collapse therapy, thoracoplasty, plumbage, and even early thoracoscopy [2]. Swiss reports of patients with Mycobacterium tuberculosis treated with thoracoplasty and extrapleural pneumothorax provided the first hope that patients could be cured of the disease. At the time, limitations of anesthetic techniques prevented much surgical intervention inside of the chest [3]. Pneumonectomy and early lobectomies were rare and crude, accomplished essentially by tourniquet techniques. With the concurrent developments of endotracheal intubation and positive pressure ventilation, more surgical options became available, and isolated single lung ventilation paved the way for the development of modern anatomic lung resection procedures. The development of antimicrobial agents quickly led to medical treatment becoming the primary therapy for the majority of patients with mycobacterial disease and surgical intervention becoming a rarity.

Today, for selected patients with mycobacterial disease, the original indications for thoracic surgical intervention still apply, although the specific surgical techniques available have evolved. Thoracoplasty, rather than a first-line technique, is reserved as a last resort for only the most challenging cases, while minimally invasive video-assisted thoracic surgery (VATS) is often the initial procedure of choice. In general, lower morbidity and faster recovery associated with minimally invasive techniques have helped to make thoracic surgical lung resection an important adjunct to antibiotic therapy in the treatment of mycobacterial disease.

Indications for Surgical Intervention

The primary treatment of patients diagnosed with NTM is a multidrug antibiotic regimen; however, a number of patients will not respond to medical therapy alone. The rate of successful sputum clearance in patients with NTM treated with antibiotics varies widely and, particularly in the case of Mycobacterium abscessus infections, can be quite poor. Furthermore, compliance with multidrug regimens over many months can be difficult due to significant side effects and, in some studies, has been less than 80% [4]. Surgical intervention and specifically anatomic resection of areas of gross cavitary disease or severe bronchiectasis can be of significant benefit in treating select patients. The goals of surgery are similar to those of antibiotic therapy and include eradication of the infection to prevent further destruction of the lung and relief of symptoms including cough, sputum production, and hemoptysis. The official ATS/IDSA statement does not list clear indications for which surgical resection is recommended, but does state that the more difficult to treat an infection is, the more likely surgery should be considered. The statement also recommends expert consultation with a multispecialty group experienced with treating NTM disease [5]. While there is no definitive statement regarding indications for surgical resection, there are circumstances in which surgical resection should be considered. Table 1 includes a list of generally accepted indications for surgical resection in patients with NTM disease. The Japanese Society for Tuberculosis (JST) has published guidelines for surgical therapy for pulmonary NTM disease in 2008 [6]. Those guidelines are similar to the generally accepted indications and are listed in Table 2.

Table 1 Indications for consideration of surgical resection

Table 2 Indications for NTM lung disease surgery (JST guidelines) [6]

Failed Antibiotic Therapy

Treatment failure has been described as no microbiologic, clinical, or radiographic response after 6 months of appropriate therapy or no achieved conversion of sputum to AFB culture negative after 12 months of appropriate therapy [5]. Based on this definition, most patients who are considered for surgery have been on a prolonged antibiotic therapy regimen of usually 1 year or more. After 1 year of unsuccessful sputum clearance, it is reasonable to consider surgical intervention as an option to continued antibiotic therapy alone. Referral of patients for surgical resection earlier in their antibiotic course can also be considered if based on expert opinion, likelihood of sputum clearance with antibiotics alone is low due to radiographic extent of disease, or patients exhibit other confounding sequalae such as unrelenting cough or hemoptysis.

Localized Disease Amenable to Anatomic Resection

Patients who are considered for surgical resection have a distribution of cavitary disease or bronchiectasis that is confined to an anatomically defined pulmonary lobe or segment. Optimally, once that anatomic area is removed, the remaining of the lung is relatively free of gross disease. Patients with diffuse involvement of both lungs are generally not candidates for resection. Depending on preoperative pulmonary function testing , however, patients with diffuse disease of one lung or bilateral disease present may be candidates for pneumonectomy or staged bilateral resections. The latter scenario is commonly seen in patients who have middle lobe and lingular bronchiectasis with sparing of the upper and lower lobes bilaterally. Patents with upper lobe involvement may also have concomitant lower lobe disease. When the lower lobe involvement is limited to superior segment, upper lobectomy with lower lobe superior segmentectomy can be accomplished to preserve the majority of the unaffected lower lobe.

Figure 1 depicts a patient with right upper lobe cavitary disease . Typically, with large apical cavities, much of the upper lobe is destroyed, and a lesser resection than lobectomy is not practical. In the lower lobe, however, it is not uncommon to have a cavity in the superior segment with sparing of the basilar segments. Patients with classic Lady Windermere syndrome, (right middle lobe bronchiectasis) or lingular involvement, are good candidates for middle lobectomy or lingulectomy via a minimally invasive or VATS approach [7]. Figure 2 shows a patient with right middle lobe and lingular bronchiectasis who had Mycobacterium avium complex (MAC) infection and presented with recurrent hemoptysis. Figure 3 shows a coronal CT image of the same patient following bilateral VATS right middle lobectomy and lingulectomy.

Fig. 1

Axial and coronal CT images demonstrating a large right upper lobe cavity and smaller cavity of the left upper lobe

Fig. 2

CT images of a patient with right middle lobe and lingular nodular bronchiectasis due to Mycobacterium avium complex disease

Fig. 3

Coronal CT image following right VATS middle lobectomy and left VATS lingulectomy

Patients Have Cardiopulmonary Fitness to Tolerate a Lung Resection

In order to be considered for lung resection, patients must have adequate pulmonary reserve to tolerate a resection and must not have other uncontrolled medical conditions that put them at a prohibitive risk for a major surgical procedure. CT imaging and pulmonary function testing are needed to determine the extent of resection and the pulmonary reserve of a candidate for resection. Nutritional status and general functional status are also important considerations. The preoperative evaluation of patients is discussed in detail below.

Hemoptysis

Hemoptysis is most commonly due to bronchiectasis. Massive hemoptysis of greater than 500 cc of blood in 24 h or greater than 100 cc of blood loss an hour requires immediate intervention [8]. Prior to the 1970s, the emergency lung resection was performed in this situation but was associated with high complication rates and mortality. Modern series demonstrate a significant reduction in morbidity and mortality with bronchial artery embolization for treatment of hemoptysis [9]. In patients with known NTM disease, who present with hemoptysis, an initial evaluation should include high-resolution CT scan and flexible bronchoscopy. Initial management includes ICU admission, cardiopulmonary stabilization, and airway management including intubation if needed. Approximately 25% of patients with massive hemoptysis for all reasons will not require intervention; half typically undergo interventional radiologic embolization [10]. Bronchoscopy, in addition to localizing the bleeding source, can provide therapeutic options for some control of bleeding. In over half of cases with hemoptysis, a bleeding site is not identified at the time of bronchoscopy [11]. CT imaging in patients with NTM disease can identify the most suspect areas of involvement localizing a potential source of bleeding and helping to guide a bronchoscopy examination.

Bronchial artery embolization is the treatment of choice for management of massive or recurrent hemoptysis [12,13,14]. Success rates for treatment of massive hemoptysis range from 75% to 99% and in studies with recurrent hemoptysis are in the range of 10–55% [15]. Urgent surgical resection is reserved for patients who have ongoing massive bleeding not controlled with other measures and should be considered as a last resort. Emergency lung resection for massive hemoptysis carries a mortality risk of 20% and morbidity as high as 50% [16]. Elective surgical resection for the primary treatment of recurrent hemoptysis associated with NTM as the primary indication for surgical intervention has been reported for about 10% of patients [17].

Large Cavitary Disease

Cavitary lesions in NTM lung disease patents can remain as reservoirs for large numbers of infectious organisms. In patients with large fibrocavitary lesions, lung destruction may progress more rapidly than in patients with primarily bronchiectatic nodular disease [5]. Antimicrobial agents do not effectively penetrate these areas and thus can continue to spread and cause further lung destruction over time [18]. Further destruction of lung can lead to continuing decline in pulmonary function until a patient no longer has adequate pulmonary reserve to tolerate resection. Resection of large cavities can reduce the mycobacterial burden and help to prevent further lung destruction. Additionally, large cavities can provide refuge for secondary bacterial or fungal infections, which can also lead to hemoptysis . Figure 4 shows CT images of a patient with cavitary disease due to MAC with a secondary mycetoma.

Fig. 4

CT image shows a large right upper lobe cavity with secondary development of a mycetoma

Severe Bronchiectasis

Severe bronchiectasis can be associated with chronic cough, daily sputum production, and hemoptysis. Additionally, patients are susceptible to recurrent secondary bacterial infections, which over time may include multidrug-resistant strains. The CT scanning is more useful that plain chest X-ray in identifying and quantifying the degree of bronchiectasis. Patients with NTM infections, who have continued symptoms and progression of disease on CT imaging, are candidates for possible lung resection. Cough and sputum production continuing over long periods can significantly impact quality of life. Lady Windermere syndrome refers to a pattern of middle lobe and lingular bronchiectasis seen with NTM infections. In a report by Yu et al. [7], a total of 134 patients underwent 172 operations, with 38 patients having staged bilateral resections. Video-assisted thoracic surgery (VATS) approach was used, and 102 middle lobectomies and 70 lingulectomies were performed. There were no operative mortalities and a complication rate of 7%. The reported cure rate with antibiotic therapy alone in similar groups ranges between 55% and 67% [5, 19, 20]. The operative group reported 84% of patients were negative for mycobacterial disease after surgical resection, and 27 patients (29%) who had operative tissue were positive for mycobacteria subsequently converted to a sputum culture-negative status [7].

Progressive Disease on Imaging

Despite appropriate antibiotic therapy, patients who have progressive disease including enlarging cavities or increasing nodular bronchiectasis should be evaluated for surgical resection. Large cavitary disease in particular tends to progress at a more rapid pace than nodular bronchiectasis. Ongoing destruction of the lung without eradication of infection can lead to worsening pulmonary function which will eventually exclude a patient from consideration of lung resection .

Recurrence of Positive Sputum Off Antibiotic Therapy

Reactivation of MAC after a period of negative sputum smear and culture has been reported in patients with nodular bronchiectasis . It has been reported that patients with NTM and bronchiectasis may be infected with multiple genetic strains [21]. When patients with MAC develop recurrent positive cultures after a period of negative sputum cultures, the infection is often due to a different genetic strain. This has led to the implication that the underlying bronchiectasis is the substrate which allows for NTM infection [22]. Lung resection in this circumstance should help to eliminate the infection and reduce the likelihood of recurrent infection, by removing the affected lung tissue.

Medication Intolerance/Non-compliance

Drug treatment regimens for NTM disease require multiple medications over extended periods. Medication side effects, intolerance, and non-compliance have been a significant factor in the treatment of patients with those infections [23]. Side effects from antibiotic regiments range from gastrointestinal upset to hepatitis and hearing loss. Weight loss and malaise can be a significant sequalae of antibiotic therapy. Continuance of antibiotic therapy in this circumstance can lead to a debilitated metabolic state, excluding the patient from possible surgical candidacy. Monitoring for side effects and toxicity is imperative for patients on undergoing long-term therapy. In patients who have difficulty maintaining a prescribed antibiotic regimen, surgical resection should be considered.

Macrolide Resistance

Two risk factors have been associated with the development of macrolide-resistant NTM disease . These include treatment of the disease with macrolide monotherapy or treatment with a macrolide and an inadequate companion medication [24]. The management of macrolide-resistant NTM requires “complex clinical decision making” and, according to 2007 ATS guidelines, should only be undertaken with expert consultation [5]. In regard to treatment of patients with macrolide-resistant MAC lung disease, the overall outcome is poor, but the treatment strategy associated with the most success included both the use of a parenteral aminoglycoside (streptomycin or amikacin) and surgical resection of disease for patients with either cavitary or nodular/bronchiectatic disease [24].

Preoperative Evaluation of Patients

When patients are referred for surgical resection, they are best considered for a procedure in the context of a multidisciplinary evaluation by a team experienced with treatment of NTM disease [5]. At a minimum, patients should have complete culture data with species identification of their infection, pulmonary function testing with FEV1 and DLCO measurements, and recent CT imaging of the chest. History and physical examination should focus on determining if patients are fit for surgery with focus on pulmonary, cardiac, nutritional, and overall physical conditions. Other medical conditions should be under good control. An initial surgical evaluation may identify areas of potential risk that require further testing or even intervention prior to undergoing lung resection.

All patients considered for resection should have undergone at least an initial regimen of multidrug antibiotic therapy prior to consideration of surgical intervention. The duration of antibiotic therapy prior to surgery is dependent on the particular organism identified, response to antibiotics, extent of disease, and the patient’s fitness to undergo a resection [25].

Pulmonary Function Testing

Most recommendations on preoperative assessment of patient’s fitness for lung resection are developed from literature focusing on patients with malignancies. While such recommendations do not apply in every circumstance, patients with NTM referred for possible lung resection are evaluated preoperatively utilizing similar testing methods. The goal of testing remains the same, to determine if patients who are considered for resection of NTM disease have adequate cardiopulmonary fitness to safely endure a lung resection. As recommended by the American College of Chest Physicians (ACCO) [26] and British Thoracic Society (BTS) [27], the initial step in evaluating patients for potential lung resection candidates is to complete pulmonary function testing that incudes spirometry and measurement of DLCO. Patients with an FEV1 and DLCO>80% can usually tolerate a pneumonectomy. Patients who have an FEV1 > 1.5 liters can usually tolerate a lobectomy [28]. Patients who do fall in these categories may still be candidates for resection; however, further risk stratification is usually recommended. Although still obtained, preoperative pulmonary functions may not be as predictive of outcomes for patients who undergo minimally invasive procedures as opposed to thoracotomy [29].

Due to the frequency of underlying lung disease in many patients with NTM disease, many patients considered for lung resection will have significantly impaired pulmonary function and will not fall into a low-risk group. Patients who undergo lung resection for infectious reasons, however, tend to lose mostly destroyed and nonfunctioning lung. Thus, the loss of cavitated and bronchiectatic lung may not result in as much a detriment to the patient’s overall lung function as one would calculate using the standard anatomic method (post-op predicted FEV1 = pre-op FEV1 *(1- # of segments resected /19). A similar phenomenon is seen in patients with severe bullous emphysema who undergo lung resection for treatment of malignancy. The concomitant lung volume reduction that occurs with removal of a severely emphysematous lobe can improve post-op lung function by decompressing the remaining functional lung [30].

When calculated post-op FEV1 and DLCO are both <30%; patients are clearly at increased risk of morbidity and mortality with lung resection for malignancy [31]. In patients with NTM disease, it is in that circumstance, with severe impairment, that eradication of infection becomes paramount to preserve the remaining lung function patients have. Every effort should be made to pursue a course that will lead to cure. Radionuclide ventilation and perfusion scanning can be helpful in more objectively predicting post-op FEV1 and DLCO [32]. In certain circumstances the lung slated for resection will contribute marginally to overall pulmonary function.

To illustrate this scenario, Fig. 5 shows the CT images and VQ scan of a patient with a large left upper lobe cavity due to Mycobacterium avium disease . FEV1 and DLCO were 28% and 32%, respectively. A VQ scan however, revealed only minimal perfusion to the left lung (Fig. 6). Since the contribution from the left lung to overall lung function was so little, this patient underwent pneumonectomy without complication and achieved negative sputum cultures.

Fig. 5

The CT images show large cavity of the left upper lobe, with an apparently spared left lower lobe

Fig. 6

Pulmonary function testing showed an FEV1 of 9 L (32% predicted) and a DLCO of 35% perfusion images from a quantitative VQ scan show that the left lung accounts for less than 15% of perfusion. The patient underwent a left pneumonectomy and recovered without incident

Cardiopulmonary exercise stress testing can also stratify operative risk for patients who based on pulmonary function are classified as high risk. Patients with a maximal oxygen consumption (VO2 max) less than 1 liter/minute are at prohibitively high risk and should not undergo resection [33]. Expressing VO2 max in terms of body mass is useful in evaluation of patients who may have had significant weight loss as an effect of long-standing NTM disease. Patients who demonstrate a VO2 max <10 mL/kg per min are at very high risk for morbidity and mortality and also should not be considered for lung resection [34]. Although patients with poor FEV1 and DLCO and reduced VO2 max are at high risk, their pulmonary function may improve with optimal medical management of their underlying lung disease and a formal pulmonary rehabilitation program [35]. Patients who are still smoking must stop and then commit to completing a formal pulmonary rehabilitation program. Following completion of the program, repeat testing can be completed to see if the patient has improved enough to be reconsidered for resection.

Cardiac Evaluation

Cardiac evaluation prior to lung surgery follows guidelines established and published by the American Heart Association for patients undergoing surgery for other non-cardiac procedures [36]. Initial evaluation starts with a complete history and physical and includes questions specifically about angina, prior cardiac events, stroke, history of valve disease, arrhythmias, smoking, peripheral vascular disease, cerebrovascular disease, stroke, hypertension, and dyslipidemia. Patients also undergo EKG and a determination of cardiac functional status. For patients with low risk, no further evaluation is needed. In patients with high risk, additional cardiac testing including echocardiography, stress testing, formal cardiology evaluation, or invasive cardiac procedures may be indicated.

Metabolic Status

Second to pulmonary function, overall metabolic status is an important consideration in patients undergoing lung resection. Chronic malaise and weight loss may result from either NTM infection or as a side effect of antibiotic therapy. Weight loss due to malnutrition can lead to increased complication rates including infection and poor wound healing. A history and physical should include questions about weight loss, diet, and a calculation of BMI. Patients should also undergo routine laboratory testing including a serum albumin. In elderly patients undergoing surgical procedure, a negative catabolic state indicated by a serum albumin of less than 2.2 g/dl has been shown predictor of poor outcomes [37]. Patients who are identified to be malnourished should be seen by a dietitian who can help define a program of nutritional supplementation to improve the patients’ overall nutritional status. In some case of severe malnutrition, feeding tube placement and enteral supplementation may be necessary prior to undergoing an operation to reverse severe malnutrition. Unlike thoracic surgical patients who undergo lung resection for malignancies, most patients with NTM disease do have ample time to optimize their metabolic state prior to surgery.

Perioperative Antibiotic Coverage

All patients undergoing surgical interventions for NTM disease must also be on optimized antibiotic coverage pre- and postoperatively to minimize the risk of postoperative complications related to poor wound healing. Ideally, patients should have sputum that is acid-fast bacilli (AFB) culture negative prior to surgery, but unfortunately, many patients are deemed surgical candidates due to the inability to accomplish sputum culture conversion with antimicrobials alone. Choosing adequate antimicrobial therapy is further impeded by the general drug resistance of NTM pathogens. Regardless, surgical candidates should be on the best antimicrobial regimen possible for as long as possible, typically at least 3 months, prior to a surgical procedure. Parenteral agents such as amikacin should be included in the antimicrobial regimen during hospitalization in the immediate perioperative period. Appropriate antimicrobials should be continued postoperatively until the patient has met the microbiologic criterion for treatment success, 12 months of sputum culture negativity while on therapy.

Surgical Techniques

The majority of patients who require surgical intervention for NTM disease do so as an adjunct to antibiotic therapy to increase the likelihood of cure. A minority of patients undergo thoracic surgical procedures to treat complications of NTM infections which can include bleeding, pneumothorax, or empyema. Indications for treatments of these complications are considered on a case by case basis. In general, major lung resection is best not performed in an emergency setting, especially when a more conservative option is available such as chest tube drainage or an interventional radiologic procedure. Once the acute issue is addressed, then patients can be evaluated for a definitive procedure.

In planning an operation for a patient with NTM disease, there are three key elements to consider including the virulence of the infection , the pattern of disease present, and the patient’s ability to tolerate an operation. An understanding of these elements will help guide decisions on timing of an operation, approach, and extent of resection.

Of the hundreds of NTM species, only a few account for lung disease that may need to be considered for surgical resection. These can be divided into fast- and slow-growing categories. Rapid-growing mycobacteria include M. abscessus, M. fortuitum, and M. chelonae. The slow-growing organisms include MAC (M. avium and M. intracellulare, M. Kansasii, M. xenopi, and M. simiae) [38]. Mycobacterium avium complex is the most commonly found respiratory pathogen. Mycobacterium abscessus can be very difficult to eradicate with antibiotics; therefore, surgical resection is typically considered earlier than for other organisms after an initial antibiotic course [5]. Similarly, with macrolide-resistant organisms, earlier surgical resection is favored.

The pattern of disease is also important in deciding the timing of surgery and the specific operation to be planned. Fibrocavitary disease tends to progress rapidly, and the large cavities serve as a reservoir of mycobacteria into which antimicrobial penetration is limited. Patients with large residual cavities after a period of negative sputum samples may tend to become positive again, due to survival of mycobacteria in those cavities. Nodular bronchiectasis pattern may be more diffuse and often involves both the middle lobe and lingula. In patients with bilateral disease, where staged resection is necessary, reassessment of fitness with repeat pulmonary function testing needs to be considered prior to a second operation.

In both disease patterns, the volume of the lung to be resected is determined by the extent of disease. The goal of surgical resection is to remove all gross areas of disease. Typically, this is accomplished with anatomic lung resection such as lobectomy or segmentectomy; however, smaller cavities may sometimes be resectable with wedge excision. All three, lobectomy , segmentectomy , and wedge resection , may be utilized in a single case to remove all areas of disease. Historically, these resections were accomplished through a thoracotomy incision, but application of minimally invasive VATS has demonstrated excellent results [39].

While the surgical approaches utilized today in the treatments of NTM have advanced to include minimally invasive procedures such as VATS , certain principles of treating patients with NTM have not changed. The goal of surgical approaches is gross resection of diseased lung while preserving as much functional lung as possible. Gross resection of any large cavities is necessary, while small areas of nodular disease can be allowed to remain if removing them requires loss of significant “normal” lung.

Thoracotomy

In planning an approach for resection of NTM disease, the preoperative CT scan is invaluable. In patients with large cavities that have destroyed much of the upper lobe and appear to extend to the chest wall, typically a thoracotomy approach is warranted. When patients have had a prior thoracotomy, the previous incision is utilized. If they have no history of prior chest surgery, then a longitudinal muscle-sparing incision is used just anterior to the border of the latissimus dorsi muscle. The latissimus is retracted posteriorly, and the serratus anterior is retracted anteriorly to expose the ribs. This muscle-sparing incision allows for the harvest of full latissimus if muscle transposition is needed. Once exposed, the chest is then entered above the fifth rib if possible. With dense fibrous adhesions, resection of a rib may be required to gain entry. A complete pneumonolysis is then performed by freeing the lung within the pleural space. The use of extrapleural dissection is avoided if possible due to the increased bleeding it causes. Electrocautery and blunt and sharp dissection are used, with meticulous technique to avoid tears in the visceral pleura. If an extrapleural approach is taken, often it is safer to enter an apical cavity to free the lung from the apex of the chest cavity and then with better visualization complete the removal of the attached cavity from the apex of the chest in the area of the subclavian artery. On occasion a second thoracotomy incision is required to completely free the base of the lung. Also, a VATS scope can be used to help visualize the base or apex of the lung when difficult to see through the thoracotomy incision.

Once the lung is free in the chest cavity, a complete assessment is made with careful palpation to identify all areas of disease. Typically, a lobectomy is performed by dividing the hilar structures with an endo-GIA stapler. Dissection in the fissure is avoided if possible, and then it is divided last with serial firings of the stapler. This technique can help to limit air leak from the remaining lung. In some cases, dense reaction in the hilum due to granulomatous nodal inflammation makes initial hilar dissection treacherous, and dissection in the fissure to identify the pulmonary artery is necessary. On rare occasions, dense reaction in the hilum will make an anatomic dissection impossible, with vascular structures being unrecognizable. In that circumstance, a combination of clamping, electrocautery, and oversewing along the clamp can be used to complete a nonanatomic resection of diseased tissue.

Once the main area of disease is resected, the lung is carefully examined, and any additional areas of disease are resected with segmentectomy or wedge resection . Tissues are cultured prior to being sent for pathologic review.

The chest is then irrigated with warm sterile water, and the lung is ventilated, while a careful inspection for air leaks is performed. Special attention is focused on bronchial stumps and other staple lines to ensure that they are pneumostatic. Any air leak from the bronchus is repaired with interrupted sutures. Air leaks from the lung parenchyma are also oversewn. An assessment is then made of any significant residual pleural space. If there is a large space not filled by the remaining lung, then a muscle flap can reinforce the bronchial closure and fill thoracic cavity. The latissimus dorsi can be used. It is usually a large muscle and provides well-vascularized bolstering of the bronchial stump while filling the apical chest cavity. It is freed subcutaneously, and then its inferior and posterior attachments are divided. With careful attention to its axial orientation, the muscle is transposed into the chest through a resected 5 cm portion of the second rib. The muscle is sutured to the bronchial stump. Figure 7 shows a patient with a large left upper lobe cavity. The patient underwent left upper lobectomy, and the remaining left lower lobe did not fill his left chest cavity well at the time of surgery. A latissimus dorsi muscle flap was transposed into the left chest. Figure 8 shows a post-op coronal CT image demonstrating good expansion of the remaining lung and filling of the apical chest cavity space with muscle.

Fig. 7

CT image showing large left upper lobe cavity, due to NTM

Fig. 8

Post-op coronal CT image following left upper lobectomy and latissimus dorsi muscle flap transposition . The remaining lung is well expanded and the apical space is filled by muscle flap

If the lung adequately fills the pleural space, following resection, then a large muscle transposition is not necessary. A pleural flap, pericardial fat pad, or intercostal muscle flap can be used to reinforce the bronchial closure. Two chest tubes are placed, one anterior and one posterior to the lung. For pain control a soaker catheter is tunneled along the rib margins and connected to a pain pump device that runs a continuous infusion of local anesthetic (On-Q pain relief system, Halyard, Irvine, CA). Alternatively, a thoracic epidural may be placed prior to the onset of the procedure.

VATS Resection

For patients with a cavity centrally located (not in contact with the chest wall) or with middle lobe or lingular bronchiectasis, a VATS approach is typically planned. Two 10 mm ports are utilized, one in the eighth interspace at about the midaxillary line and one in the sixth interspace anteriorly. A utility incision of about 4 cm is made in the fourth interspace. A soft tissue retractor is used (Alexis retractor, Applied Medical, Rancho Santa Margarita, CA) at the utility incision site, without rib spreading. A complete mobilization of the lung is performed if adhesions exist. The mediastinal pleura is opened using electrocautery. The pulmonary vein branch to the lobe to be resected is then divided using an endo-GIA stapler. Next the pulmonary artery branches are similarly divided with staplers and finally the bronchus. The remaining fissure is then divided, and the lobe is then placed in a plastic endo-bag and removed though the utility port. Water is instilled and an inspection for air leaks is undertaken. Any leaks are addressed. Pericardial fat pad, pleura, or intercostal muscle flaps can be used to cover the bronchial stump. The port incisions are all thoroughly irrigated to minimize abscess development, especially with M. abscesses infections. Figure 9 shows closed VATS incisions following lingulectomy.

Fig. 9

Operative photo showing closed VATS incisions following lingulectomy . A chest tube is exiting the middle port site. The ruler is near the utility incision. A small pain pump catheter exits posteriorly

Bronchial Coverage

Reoperation and treatment of bronchopleural fistulas is difficult and associated with significant morbidity and mortality. To avoid that complication, routine flap coverage of the bronchial stump can be employed. There are a number of tissue flap options for coverage of bronchial stumps. A pleural flap is relatively easy and does provide vascularized tissue coverage of the bronchial stump. Due to dense pleural adhesions in many patients with NTM disease, a viable pleural flap may not be available following mobilization of the lung. The pericardial fat pad can be used when pleura is not available. Mobilization of the pericardial fat pad is accomplished by elevating the fat from the pericardium starting inferiorly. The upper portion of the pad remains intact and vascularized from branches from the internal mammary artery. It is a good choice for use in covering a middle lobe bronchus, although it can be used to cover any airway closure. Pedicle intercostal muscle flap also provides good vascularized tissue coverage of bronchial closures. The flap can be harvested during the time of a thoracotomy or via a minimally invasive technique [40]. It remains an option in patients who have had a previous thoracotomy involving division of the latissimus dorsi muscle. Latissimus dorsi muscle flap provides well-vascularized muscle coverage as well as helps to fill the pleural space. The muscle flap is created by freeing the latissimus from the skin and then detaching it from the iliac crest inferiorly and spine posteriorly. Creation of a large skin flap in harvesting the muscle can result in the development of post-op seroma. A subcutaneous drain is left in the bed of the latissimus when transposed until drainage remains low.

Thoracoplasty

Thoracoplasty remains as an option for dealing with complicated space issues. The Schede thoracoplasty was originally described as a collapse mechanism in which ribs and intercostal muscles were resected allowing collapse of pectoral muscles and skin [41]. Alexander described extrapleural thoracoplasty in which the ribs were resected, but periosteum, intercostals, and pleura were preserved [42]. While effective in eradicating infected spaces and airway fistulas, thoracoplasty can be disfiguring and over the long-term lead to scoliosis and chronic pain. Today, thoracoplasty is not usually employed as a primary maneuver to treat patients with NTM, but is generally reserved for management of a complication such as empyema or bronchopleural fistula.

Post-op Management

Postoperative management of patients who undergo lung resection for NTM disease is similar to patients who undergo lung resection for other indications. Typically, patients are admitted to the ICU post-op and are monitored closely for adequate respiration and bleeding. Adequate pain control allows early mobilization and participation in physical therapy. Patients are educated on the use of an incentive spirometer and receive regular respiratory therapy evaluation with encouragement to cough and expectorate. Oral mucolytics, nebulized hypertonic saline or mucomyst, and chest physical therapy are used regularly. Chest tubes are kept to −20 cm suction until air leaks resolve and then are placed to water seal. Chest tubes are removed when there are no air leaks, and daily drainage is less than 250 cc per 24 h.

Air Leaks

One of the most common complications with lung resection in NTM patients has been air leak . This often occurs due to the scarring and fibrosis caused by chronic infection. Dense adhesions may be present throughout the pleural space to the point where the entire pleural space is obliterated. Extrapleural dissection can result in significant bleeding, but intrapleural dissection can result in visceral pleural tears which then leak air. Meticulous intra-op technique to avoid tears is important in avoiding prolonged air leak, but a complete pneumonolysis is essential to allow full expansion of the remaining lung. A combination of electrocautery and sharp and blunt dissection is utilized to free the lung. Avoidance of excessive dissection in incomplete fissures also helps to avoid air leaks. Hilar structures are first identified and divided using stapling devices, and then the fissure can be divided with a stapler. Careful attempts at identification and intervention to stop air leaks at the time of surgery is best way to avoid the reoperation.

For small air leaks which do not resolve after 5 days, chest tubes can be placed to Heimlich valve. Serial chest X-rays are done to determine if the patient’s lung will remain expanded without continuous suction. If so, the patient may be discharged with a chest tube in place and reevaluated for chest tube removal as an outpatient. Most small air leaks with no large residual space can be managed conservatively. When patients have a large persistent air leak beyond 14 days, develop a large pneumothorax off of suction, or have a large residual space, re-exploration is usually considered. An inspection is performed, and an attempt at direct closure of the leak, additional tissue flap bolstering, or thoracoplasty may be required.

Endobronchial valves (Spiration, Olympus Respiratory, USA) have received an FDA Investigational Device Exemption for use with air leaks after lobectomy or segmentectomy. Figure 10 shows the IBV valves, and Fig. 11 shows a bronchoscopic view following deployment. In patients with persistent air leak, bronchoscopy is performed, and a systematic balloon occlusion of the airways is performed while carefully watching the water seal chamber for a change in air leak, as evidenced by decreased bubbling. Once the airway or airways contributing to the air leak have been identified, IBV valves are deployed. The patient’s chest tube can be removed once complete resolution of air leak is confirmed. The valves are left in position for 6 weeks, and then the patient returns for outpatient bronchoscopy and retrieval of the valves.

Fig. 10

IBV valves

Fig. 11

Two IVB valves following deployment

Outcomes with Pulmonary Resection for NTM Disease

In general, there have been good results with surgical series for NTM disease. Table 3 summarizes some of the largest modern series. The vast majority of patients included in these reports had MAC infections. A smaller number patients had M. abscessus infections. Mortality ranges from 0% to 23% with sputum conversion being reported at 54–100%. The morbidity associated with lung resection ranges from 8% to 50%. Centers with more experience tend to have the lowest morbidity and mortality rates. Patients with nodular bronchiectasis more frequently undergo VATS and tend to have fewer complications. Wound complications and infections tend to be higher in patients with M. abscessus infections. Overall survival rates are good, but in general morbidity following lung resection for NTM disease is high and ranges from 5% to 50%. In comparison, a review of the STS database including 20,657 lobectomy cases from 231 centers, mostly for malignant indications, demonstrated a 1.5% mortality rate and 9.6% major complication rate [55].

Table 3 Surgical outcomes for NTM surgery

Late Complications

Most bronchopleural fistulas are identified early but may present late, even years following the original operation. Patients may present with a range of symptoms ranging from mild to severe sepsis. An enlarging air-filled cavity or air- and fluid-filled cavity is a common radiologic finding. Patients may admit to increased cough, sputum production, or even a bubbling sensation in their chest. CT scanning and bronchoscopy are done to assess the location of the fistula. Ventilation scan can also help determine if a gas-filled space is truly in continuity with the airway. Reoperation is required to drain any infection and close the fistula. Typically, direct closure is quite difficult, and tissue flap buttressing to the area of fistula is necessary.

Wound Infections

Subcutaneous infections due to NTM can occur following surgical resection. The most common occur with M. abscessus. Careful irrigation of incisions is important at the time of surgery, and use of tissue protectors and specimen bags for minimally invasive procedures limits contamination. When patients present with a draining wound, incision and drainage with culturing is the initial step. Bacterial infections can usually be treated with drainage, packing, and antibiotics based on culture results. Mycobacterial infections may require wide local excisional debridement and reclosure.

Extrapulmonary Surgical Infections

NTM infections in children may present as painless head and neck lymphadenopathy which involves the skin. The most common NTM pathogen is MAC. Proposed treatments have included antibiotics alone, aspiration, incision and debridement, or surgical excision. The best results in regard to healing favor surgical excision [56]. Excision can be associated with nerve injury, and as an alternative to excision, incision and drainage with a course of antibiotics may be an option when the risk of nerve injury is high.

Mycobacterium marinum is an endemic fish pathogen which is present in aquatic environments. Human infections can occur with skin injuries that are exposed to contaminated water, fish, or shellfish. The American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) guidelines recommend two active agents (clarithromycin/azithromycin, ethambutol, or rifampin) for 3–4 months with adjunctive surgical debridement for invasive infections [5]. In a recent series and review, only 44% of superficial skin infections required surgical excision, while 95% of invasive infections (tenosynovitis or septic arthritis) required surgery [57].

Infection of cardiac surgical wounds and diffuse systemic infections have also been reported in cardiac surgical patients who were exposed to NTM from the heater/cooler units used with cardiopulmonary bypass . Mycobacterium chimaera, a member of the M. avium complex, has been cultured from municipal water supplies. That water when used in the reservoir of the heater/cooler equipment can become a source of contamination for patients undergoing cardiac surgery. Prosthetic valve endocarditis , local wound infections, and systemic disease have occurred as a result of exposure. Infections were fatal in four of ten reported cases [58].

NTM infections have also been reported following plastic surgical procedures [59], eye surgery [60], vascular surgery [61], and other surgical procedures. There is variability in the management based on the specific infection and location. When surgical implants are present, they may require surgical removal in addition to antibiotic therapy to resolve the infection [62]. In non-healing and recurrent wounds, a high index of suspicion is needed as standard bacterial wound cultures will not identify NTM organisms. AFB stains and cultures must be specifically obtained. Accurate diagnosis is key to guiding appropriate antibiotic therapy with surgical intervention.

Conclusion

Surgical resection for NTM infections has a reputation of being an option of last resort. This may be partly due to the historical treatment of mycobacterial tuberculosis with collapse therapy and disfigurement that patients had to endure with thoracoplasty. In centers with experienced multidisciplinary teams, modern thoracic surgical techniques can be utilized in patients with NTM disease to achieve a cure and resolve symptoms. Minimally invasive video-assisted techniques have demonstrated excellent outcomes, with fewer complications and faster recovery. Surgical resection is an effective and important adjunct to treating selected patients with NTM infections.