105: Adjuvant Surgery for Tuberculosis

Pulmonary tuberculous diseases are contagious infections caused by bacterial organisms or bacilli of the Mycobacterium family (Mycobacteriaceae). The most common species is tuberculosis but other types produce similar pathologic changes. The disease is spread by the aerolization of respiratory secretions, and infection occurs by inhalation of the tubercle bacilli (TB). Not everyone infected with TB will become sick immediately. Most patients are asymptomatic because of the host's immune-cell-mediated defense mechanisms, which entrap and wall off the bacilli, thereby containing the infection. The isolated bacilli may form granulomas which may lie dormant for years. Others will experience a short illness associated with malaise, low-grade fever, cough, and weight loss. If the body's immunity becomes compromised, a full-blown infection may ensue. Most frequently, these patients will develop extensive pulmonary infiltrates with a febrile illness and dyspnea associated with the concomitant pneumonia. If the walled-off granulomas break down, cavities form and accumulate secretions causing a productive cough. Infection of the pleural lining (pleurisy) may result in chest wall pain or pleural effusions with shortness of breath. Spontaneous pneumothorax may occur as a consequence of excessive coughing and will present with acute dyspnea. Long-standing infections may result in parenchymal destruction, bronchiectasis with erosion into adjacent pulmonary arteries (Rasmussen's aneurysm)¹, and massive hemoptysis.² These large cavities may lead to secondary fungal infection with Aspergillus (see Chapter 102). In some patients, extensive lung destruction can produce chronic lung collapse and contraction.

The World Health Organization estimates that one-third of the world's population is currently infected with TB bacillus and 5% to 10% of those infected become infectious or sick at some stage during their lifetime. Individuals with HIV/AIDS are most at risk for developing the full-blown infection. The largest number of new cases of TB in 2010 occurred in southeast Asia (35%); however, the incidence of new cases in sub-Saharan Africa is nearly twice that of southeast Asia with 350 cases per 100,000 people. In 2009, over 1.7 million individuals died from TB. Although the incidence of TB appears to be stable or falling, adjusted for population growth, the number of new cases is rising annually (Table 105-1).³

The US Food and Drug Administration currently approves 10 drugs for the treatment of TB. Of these, the core first-line treatment for active TB includes isoniazid, rifampin, ethambutol, and pyrazinamide. Regimens have an initial treatment phase of 2 months, followed by a continuation phase of 4 to 7 months. Treatment completion is determined by the number of doses ingested over a given period of time. Modifications to this basic regimen are made under special circumstances including HIV infection, drug resistance, pregnancy, and in pediatric patients.⁴

The surgical treatment of TB is reserved mainly for treating the complications of the disease arising from previous surgical treatment or progression of the underlying disease and secondary complications of chronic infection. Occasionally, the diagnosis of TB is an incidental pathologic finding after resection of a pulmonary nodule or mediastinal lymphadenopathy. The surgical treatment of chronic constrictive pericarditis or pleural effusions with or without lung entrapment also may reveal unexpected TB. Strains of multidrug-resistant (MDR) TB have been documented with resistance to all first-line drugs and multiple second-line drugs for which adjuvant surgery may be considered.⁵ The remainder of this chapter focuses on surgical treatment specific to the complications of previous operations or secondary complications of chronic infection that necessitate surgical intervention.

Thoracoplasty

Toward the end of the nineteenth century, it was thought that healing of tuberculous cavities would be facilitated by collapse of the lung and thoracoplasty. It was hoped that this operation would promote scar retraction of the tuberculous cavities and subsequent healing. Schede thoracoplasty was widely practiced up to the late 1930s. The thoracoplasty operation is covered in Chapter 106.

The operation, as originally described, became obsolete with the advent of pulmonary resections and drug therapy in the 1940s. In this operation, the infection is controlled by tube thoracostomy drainage or a Clagett window as an initial procedure. Subsequently, the residual space is obliterated by filling the cavity with antibiotics and closing the window or leaving the patient with a permanent window.

In recent years, closure of a residual space or bronchopleural fistula, if present, is accomplished by the interposition of various types of muscle flaps or an omentoplasty.⁶ Still, there are some surgeons who continue to perform a limited thoracoplasty with intrathoracic muscle transposition.^7,8 Other investigators have performed a cavernostomy combined with a muscle flap transposition as a single-stage procedure.⁹ The overall success rate for the control of infection and obliteration of space issues is about 75% for TB.¹⁰

Plombage Therapy and its Late Complications

In 1926, Tuffier described a procedure called apicolysis whereby a space was created using an extrapleural or extrafascial dissection and the space was filled with the patient's own fatty tissue. This operation formed the basis of extrapleural plombage collapse therapy, whereby the space was filled with heated paraffin or Lucite balls. Plombage therapy fell out of favor because of long-term complications. These have included infections, migration of these balls with erosion through the chest wall possibly into adjacent lung parenchyma, vascular structures or organs like the esophagus, and compression of the brachial plexus. Plombage therapy has been completely abandoned as a treatment of residual pleural spaces and removal of the foreign material is recommended whenever such patients are identified, as long as the operative risk is acceptable.^11,12 Subsequently, the space is handled by transposition of muscle flaps with or without a limited thoracoplasty.

Lung Destruction, Extensive Bronchiectasis, Residual Disease

Unilateral partial or complete lung destruction is a well-recognized complication of chronic tuberculous lung infection. It is rarely seen in the developed world today but may still be encountered in patients from less developed countries. Usually, it is a consequence of failure of diagnosis, poor compliance, or inadequate medical therapy for primary tuberculosis. It is characterized by extensive scarring with fibrosis and contraction of the underlying lung. The underlying parenchyma is destroyed with multiple cavitations and extensive bronchiectasis. These patients present with general debilitation, productive cough, shortness of breath, and may have massive hemoptysis. The left side is more frequently involved.

Lobectomy or pneumonectomy should be considered when the underlying lung is destroyed, but these are high-risk operations and patients need to be started on adequate antituberculous therapy prior to undertaking surgical resection. Adequate preoperative preparation including nutritional support also must be provided. Careful intraoperative planning and technical expertise is essential. These patients are at high risk for developing a bronchopleural fistula, and satisfactory coverage of the bronchial stump with a muscle flap is imperative. A space issue following resection may necessitate the use of rotational muscle flaps with or without a limited thoracoplasty. Occasionally, the obliteration of the pleural space with extensive scarring and contraction will render an anatomic lobectomy or intrapleural pneumonectomy technically very challenging and high risk. In such circumstances, an extrapleural pneumonectomy should be considered.¹³

A retrospective review of 172 cases of destroyed lung was analyzed by Bai et al.¹⁴ The ages ranged from 7 to 72 years with a median of 38.4 years. The male-to-female ratio was roughly equal. Forty-nine patients had sputum positive for Mycobacterium tuberculosis preoperatively yielding a positive TB rate of 28.5%. Of the group, 116 cases had destroyed left and 56 had destroyed right lungs. In all, 110 patients underwent a complete pneumonectomy, 37 an extrapleural pneumonectomy, and 11 lobectomy. Eleven patients developed bronchopleural fistulae and four had subsequent thoracoplasties because of persistent infection or empyema. The overall perioperative mortality rate was 2.9% with an 18.6% complication rate. The sputum negative conversion rate was 87.8% and clinical cure 91.9%.¹⁴

Drug-Resistant and Other Forms of TB

Although chemotherapy is considered the first-line treatment for pulmonary TB, surgery should be entertained for MDR disease as demonstrated in the Case Report. Usually, these patients have persistent positive sputum with extensive parenchymal disease in the face of appropriate drug therapy over a 3-month period.¹⁵ Operations have included segmentectomy, lobectomy, and pneumonectomy. The complications have included bronchopleural fistulae, especially with right pneumonectomy, and postoperative empyema.¹⁶ Adjuvant therapy is continued for 18 to 24 months after surgery and the mortality has ranged from 0% to 4.3% with a cure rate of 94% to 100%.^17,18 Nontuberculous pulmonary mycobacterial disease, especially Mycobacterium avium complex, is encountered more frequently. The introduction of macrolide-containing regimens has improved the outcomes but resistance remains a problem and pulmonary resection during the early stage of the disease should be considered for those patients who are good surgical candidates.¹⁹

Pleural Disease

Pleural effusions secondary to TB may be seen in young adults with an immunocompromised condition like HIV/AIDS and is associated with 5% of M. tuberculosis infections. The diagnosis of TB depends on the demonstration of acid-fast bacilli (AFB) in the sputum, pleural fluid, or pleural biopsy specimens; biochemistry of the fluid (pH <7.2, adenosine deaminase); and PCR testing.²⁰ For a simple unilocular effusion, tube thoracostomy and antituberculous chemotherapy is all that is necessary. Patients with complex parapneumonic effusions may benefit from the addition of intrapleural fibrinolytics and possibly surgical intervention.²¹ True tuberculous empyema is a more chronic condition and is suspected on CT scan findings of a thick, calcified pleural rind associated with loculated pleural fluid positive for acid-fast bacilli. Surgical intervention with decortication to reexpand the entrapped lung and drainage followed by antituberculous chemotherapy is warranted. These operations may be very difficult to perform and often are complicated by bronchopleural fistulae or chronic drainage.²² The role of steroids for pleural tuberculosis remains controversial.²³

Hemoptysis

Hemoptysis secondary to pulmonary tuberculosis can be catastrophic and is a common cause of morbidity and occasional mortality. Most often, bleeding occurs because of the bronchial collaterals that feed the infected cavities. Sometimes, pulmonary vessels may become incorporated into the walls of these cavities leading to small dilations (Rasmussen's aneurysms), which may erode. Rarely, bleeding occurs secondary to necrosis of small pulmonary veins or ulcerations of the bronchial mucosa. The management of hemoptysis secondary to tuberculosis does not differ from that described in Chapter 82, Hemoptysis and Lung Cancer. Bleeding may be classified as mild (<200 mL/day), moderate (200–400 mL/day), or severe (>600 mL/day). In a study of 59 patients with tuberculosis-related hemoptysis, thoracotomy was performed urgently in 21 with massive bleeding, within 2 days in 22 of 24 with moderate bleeding, and within 4 days in 14 with mild bleeding. Cavitary lesions were demonstrated in all patients with massive bleeding, 22 with moderate bleeding, and 3 with mild persistent bleeding. Four patients had a pneumonectomy, 39 a lobectomy, and 16 a segmentectomy or wedge resection. The overall mortality was 6.8% Three patients developed empyema or bronchopleural fistulae.²⁴ Others have recommended early surgical resection of persistent tuberculous cavities to avoid life-threatening hemoptysis.²⁵

Cavernoma

The presence of cavities in the setting of tuberculosis is thought to be a post primary phenomenon secondary to endobronchial obstruction. It is a rare occurrence today but was often seen in the era prior to the introduction of antibiotics. Cavities begin as an exudative process as a result of obstructive pneumonia and caseating necrosis. Tissue breakdown leads to the formation of cavities.²⁶ These cavities may be seen in patients who are immunocompromised or who have concomitant tumor. The walls of the cavities are made up of scar in which Rasmussen's aneurysms may form.¹ These cavities may be a site for reactivation and are associated with bleeding or aspergilloma formation. Therefore, surgical intervention is recommended. The operation will depend on the degree of debilitation and may involve resection or cavernostomy with intrathoracic muscle flap transfer. Rarely, a thoracoplasty is used to treat these patients. These operations are high risk and may be associated with cavity reformation, bronchopleural fistulae, and bleeding. The success or failure of the operation is associated with the cavity size, number of bronchopleural fistulae, and drug resistance.⁹

Lung Cancer

Increased risk of developing a lung cancer in a patient with primary tuberculosis has long been suspected. In a population-based cohort study, the incidence of lung cancer was significantly higher in pulmonary tuberculosis patients compared with controls (269 of 100,000 person-years vs. 153 of 100,000 person-years).²⁷ Another study has demonstrated an 11-fold increase in lung cancer in patients with tuberculosis.²⁸ More recently, an association has been shown between tumor epidermal growth factor receptor (EGFR) mutation and pulmonary TB in patients with adenocarcinoma of the lungs.²⁹ Tuberculosis may result in scar formation, and the development of carcinomas is well known. Also, the development of lung cancer in this setting may result from debilitation and the overall immunocompromised state of the patient. Recently, vigilance in patients with a history of tuberculosis has been recommended.

Endobronchial Tuberculosis and Bronchial Obstruction

Endobronchial tuberculosis is defined as an infection of the tracheobronchial tree. It is seen in 10% to 40% of patients with active tuberculosis.³⁰ It is associated with cough, sputum production, wheezing, dyspnea, and hemoptysis. It may be difficult to diagnose because it is not obvious on chest x-ray. Bronchoscopic sampling is the key to diagnosis. Early treatment of this condition is nonsurgical and involves the eradication of the tubercle bacillus with antibiotics.³¹ If this condition goes unrecognized, it can lead to bronchial stenosis which, in the early phase, can be treated with steroids, but further delay results in scarring. How this is managed depends on the extent of the resultant deformity and may involve an endobronchial intervention such as stenting, laser therapy, or surgical intervention with bronchoplastic procedures.³²

Tracheoesophageal or Bronchioesophageal Fistula

Rarely, tuberculosis can cause erosion of an infected mediastinal lymph node, the airway, or esophagus. Usually these complications can be managed with endobronchial interventions, such as stenting, and antituberculous drugs. More complex lesions may require surgical intervention, which would include closure of the esophageal defect, resection of the involved airway, and tissue interposition.³³

A case of transcontinental spread of MDR Mycobacterium bovis in Canada was successfully treated with a combined medical–surgical approach.⁵

A 49-year-old white female from Alberta, Canada traveled to Spain in the spring of 1996 to care for a terminally ill relative with acquired immunodeficiency syndrome (AIDS) complicated by TB. Her visit lasted about 5 weeks, whereupon she returned to Canada. About a year and a half later, in November of 1997, she developed a cough for which she sought medical treatment. The physical exam revealed a healthy-appearing woman with no predisposing factors for TB, other than the immunocompromising condition of noninsulin-dependent diabetes. HIV serology was negative and CD4 lymphocyte count was normal (1.0 × 10⁹/L). The history was negative for travel other than the previously described visit to Spain. A plain chest x-ray revealed a number of well-defined nodules bilaterally, primarily in the upper lung zones. Chest CT confirmed the presence of at least seven widely distributed nodular lesions, two of which had small central areas of cavitation (Figs. 105-1A,B and 105-2). Nonetheless, direct microscopy of sputum was negative for acid-fast bacilli (AFB). PPD, which had been performed 3 months before and 3 months after travel, and again on presentation in November, was negative. Thoracoscopic biopsy of the right-sided lesions demonstrated caseating granulomas on histopathology. Subsequent tissue and sputum cultures were positive for M. tuberculosis on DNA probe (Gen-Probe Accuprobe).

The patient was placed in respiratory isolation and started on standard antituberculous drug therapy consisting of isoniazid 300 mg, rifampin 600 mg, pyrazinamide 1500 mg, and ethambutol 1200 mg together with vitamin B6, 25 mg once daily. Subsequent microbiological study revealed the organism to be M. bovis. Drug susceptibility testing indicated resistance to all first-line drugs (M. bovis is characteristically resistant to pyrazinamide). Of the 26 available second-line drugs, the isolate was resistant to all except cycloserine and clofazimine.

The patient spent 5 months in respiratory isolation (November 1997–April 1998) where multiple sputa (n = 12) were culture-positive for the same isolate. However, all remained negative for AFB on direct microscopy. Repeat CT scan in January revealed two persistent cavitations with localized disease, perhaps accounting for the AFB negativity, that had clearly progressed, albeit slowly, over the past 3 months. Standard therapy was discontinued in February after the second-line susceptibility testing became available, and the patient was started on a new regimen consisting of cycloserine 500 mg twice daily, clofazimine 300 mg once daily, and trimethoprim-sulfamethoxazole, two single strength tablets twice daily.

Given the strength of the patient's resistance to first-line chemotherapy, the relatively weak second-line regimen, and the urgent need to prevent spread of this organism in the community, bilateral wedge resection for organism eradication was planned in two staged procedures, while drug therapy was continued. The surgery was performed under (level 4 biosafety precautions) to prevent nosocomial spread of infection. In mid-March 1998 and mid-April 1998, the left and right thoracotomies were performed, respectively, and all visible disease was resected. Prior to thoracotomy, bronchoscopy was performed to remove secretions. AFB were present on smear and M. bovis was cultured from the right apical and left superior segmental lesions, as well as from the right lower lobe lesion. The strain was eventually found to be identical to the strain isolated from the patient's relative in Spain and identical to the M. bovis strain documented in multiple HIV-seropositive patients in Spain (Fig. 105-2).

After a 4-month hospitalization, the patient was discharged in May 1998 under direct observation therapy. All sputa collected after the second thoracotomy remained negative for AFB on smear and culture and no new lesions were demonstrable on CT follow-up 1 year later.

None of the patient's 80 known contacts in Canada developed or tested positive for TB at 1 year follow-up. Although sputum-smear-negative cases of pulmonary TB are not likely to infect others, the identification of this MDR strain of M. bovis was unprecedented in Canada, and presumably the United States, prompting a conservative approach with surgical intervention. In the modern era, pulmonary infections with bacterial organisms or bacilli of the Mycobacterium family are usually amenable to medical treatment with first-line antimycobacterial drugs. The most common species is tuberculosis but other strains produce similar pathologic changes. In strains that involve multiple drug resistance to first and/or second-line agents, surgery is a recognized treatment option, after 3 months of antituberculous drugs.

A third of the world's population is currently infected with TB. Individuals with a normal immune system can generally ward off infection by segregating the bacilli, which then lie dormant for the patient's lifetime. Of the approximately 10% to 15% that develop full-blown infection, patients with HIV/AIDS or other conditions that compromise the immune system are most susceptible. Although chemotherapy remains the first-line of therapy, surgery has a role in treating the complications of disease such as those caused by previous surgery (e.g., bronchopleural fistulae), disease progression (e.g., bronchial obstruction), or the secondary complications of a chronic infection (e.g., empyema). Operations may range from simple tube thoracostomy to segmentectomy, lobectomy, or pneumonectomy. Surgeons must be vigilant for exposure to bacilli of the Mycobacterium family during any surgical procedure. For example, TB may be an incidental finding on pathology after resection of a pulmonary nodule or mediastinal lymphadenopathy. TB also may be encountered when treating patients for pleural effusions. Given the urgency of preventing the spread of this infectious disease to the community, adjuvant surgery has an occasional role in patients with MDR TB, after first- and second-line antituberculous therapies have failed.

Surgical therapy for tuberculosis infections of the lung is primarily for complications of the disease such as hemoptysis, bronchopleural fistula, chronic infections due to resistant organisms or failure of antibiotic therapy to control the disease.