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Lung Resection for Multidrug-Resistant Tuberculosis

Cardiothoracic Surgery, Inkosi Albert Luthuli Central Hospital Mayville, South Africa

For reprint information contact: Rishen Naidoo, MBChB Tel: 27 31 240 2114 Fax: 27 31 240 2113 Email: rishendran{at}mweb.co.za, Cardiothoracic Surgery, Inkosi Albert Luthuli Central Hospital, Private Bag X03, Mayville 4058, South Africa.

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
The emergence of multidrug-resistant tuberculosis poses a serious challenge to traditional drug therapy. In view of the relapse rate of up to 50% following medical management, there has been renewed interest in the role of surgery for this problem. We report our experience with lung resection for this condition. Over a 5-year period, resection was performed in 23 patients who were diagnosed with multidrug resistance after completing a course of standard chemotherapy and at least 3 months of second-line therapy. Pneumonectomy was performed in 17 patients and lobectomy in 6. There was no operative or postoperative mortality. Major complications developed in 4 patients (17.4%): 2 had post-pneumonectomy empyema and 2 underwent rethoracotomy for bleeding. Ten patients were sputum positive preoperatively, and only 1 remained positive after surgery. The patients were put on appropriate chemotherapy and followed up for 18 months. The cure rate was 95.6%. Pulmonary resection can be considered as an important adjunct to medical therapy in carefully selected patients: those who have localized disease with adequate pulmonary reserve, or who have multiple previous relapses, or whose sputum remains positive after 4 to 6 months of appropriate medical treatment. Surgery offers high cure rates with acceptable morbidity and mortality.

	INTRODUCTION

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The management of tuberculosis (TB) has been evolving since Mycobacterium tuberculosis was first isolated by Koch in the 1880s. Traditional therapy then involved surgery. By the 1960s, the introduction of chemotherapy provided a cure rate of up to 95% in patients with susceptible strains.¹ However, inadequate first-line therapy, poor patient compliance, lack of monitoring, and the prevalence of the human immunodeficiency virus (HIV) have led to the emergence of multidrug-resistant TB (MDR-TB).² MDR-TB is defined as TB that is resistant to rifampicin and isoniazid and associated with lower response to chemotherapy and higher mortality. Furthermore, it has a relapse rate of up to 50%, prompting the use of drugs that are expensive and have more side effects. Consequently, there is renewed interest in surgery as a therapeutic alternative. In this report, we review our experience in managing MDR-TB patients by lung resection.

	PATIENTS AND METHODS

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This retrospective study covered the period January 1996 to December 2000. Cases of MDR-TB treated by resection at the Cardiothoracic Unit in Wentworth and King George V hospitals in Durban, South Africa, were evaluated. The indications for surgery were as follows: sputum remaining positive after 4 to 6 months of appropriate second-line medical treatment, 2 or more previous relapses on second-line therapy, and evidence of localized radiographic bronchiectasis or lung destruction that served as a focus for recurrent infections.

The patients’ demographic characteristics and details of chemotherapy were documented. Preoperative assessment included a full blood count, blood urea and electrolytes, erythrocyte sedimentation rate, and sputum smear examination for acid-fast bacilli. HIV testing was undertaken with pretest counseling and informed consent. Chest radiography, pulmonary function tests, and high-resolution computed tomography were performed routinely. Ventilation–perfusion scanning was done when there was concern over the function of the residual lung tissue. All the patients had received a course of standard chemotherapy consisting of Rifafour (which contains rifampicin, isoniazid, pyrazinamide, and ethambutol) for 2 months followed by Rifinah (which contains rifampicin and isoniazid) for a further 4 months as well as a minimum of 3 months of appropriate second-line therapy.

Standard pulmonary resection was performed through posterolateral thoracotomy incisions with both pre- and postoperative bronchoscopy. Bronchial isolation was achieved with double-lumen endotracheal tubes in adult patients. The bronchial stump was closed with interrupted absorbable Vicryl suture (Ethicon, Somerville, NJ, USA). Reinforcement of the bronchial stump was not routinely done. In patients undergoing pneumonectomy, an intercostal drain was left in situ for 24 hours. It was repeatedly clamped for 55 minutes and unclamped to drain for 5 minutes. This strategy allows detection of excessive bleeding and stabilization of the mediastinum. Intercostal drainage following lobectomy was continued until there was re-expansion of the lung and the effluent was minimal.

Specimens were submitted for histology and culture for acid-fast bacilli. The patients were followed up on a monthly basis at the MDR clinic until they had completed an 18-month course of chemotherapy prescribed based on the drug sensitivity patterns of the organisms. Cure was defined as the absence of disease at the end of the follow-up period.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
A total of 23 patients with MDR-TB underwent lung resection during the study period. The mean age was 30.4 years (range, 2 to 69 years). There were 12 males. Blood test results were essentially normal with a mean hemoglobin level of 10.2 g·dL^–1 (range, 9.6 to 12.3 g·dL^–1). Nine patients (39.1%) were operated on for localized bronchiectasis, 4 (17.4%) for multiple previous relapses, and 10 (43.5%) for persistent sputum positivity after treatment for 4 to 6 months.

Pneumonectomy was performed in 17 cases, 12 of which were left-sided, and lobectomy was carried out in the other 6 cases. The bronchial stump was closed with interrupted suture and reinforced with intercostal muscle flaps in 2 cases as preferred by the surgeon. Stapling was not done in any patients.

Sputum conversion was achieved in 9 of the sputum-positive patients, giving a conversion rate of 90%. Complications included post-pneumonectomy empyema without the presence of bronchopleural fistula in 2 patients (8.7%), both of whom were sputum positive preoperatively. One of these patients was HIV positive and was managed by drainage alone. This patient had an empyema preoperatively. The other patient was managed by open drainage and subsequent sterilization of the pneumonectomy space. Bronchial stump reinforcement had not been done in these patients. Another 2 patients (8.7%) required rethoracotomy for bleeding. Minor complications developed in 2 patients in the form of superficial skin sepsis, which was managed with antibiotics and wound dressings. The overall major morbidity rate was 17.4%.

Four patients were HIV positive, all with CD4 counts above 400 cells·mm^–3. One of them underwent lobectomy, while 3 had pneumonectomy. The patient who remained sputum positive after surgery was HIV positive.

There was no operative or postoperative death. None of the patients who were successfully treated had a relapse during the follow-up period. Cure was thus achieved in 95.6% of patients.

The resected lung tissue demonstrated features of active TB in all patients, based on the presence of caseating granulomatous inflammation. Bronchiectasis was present in 4 specimens and aspergillosis in another 3 specimens. The culture results of the resected lung specimens could not be traced for many of the patients. The predominant feature observed in the cultures was resistance to rifampicin, isoniazid, and ethionamide in 5 specimens and resistance to streptomycin in another 4 specimens.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
With the success of medical therapy for TB, it is not surprising that surgery has largely been limited to emergency cases, such as in the presence of hemoptysis. Surgery may also be indicated in cases where a tumor cannot be excluded, or when the patient fails to respond to medical treatment.

Surgery has been advocated to remove the focus of resistant acid-fast bacilli, which are protected against chemotherapy by the surrounding fibrosis and inflammation. However, as it may be difficult to determine the exact location of the resistant organisms, this role is in question.³ Whereas the infected lung may appear normal on plain chest radiographs, TB may be diagnosed by high-resolution computed tomography in up to 91% of cases,⁴ hence its routine use in our unit.

The predominance of left-sided resection in this series is in keeping with other reports.^3,5,6 It has been suggested that the more horizontal course of the narrower left main bronchus and the smaller peribronchial space contribute to the left lung being more commonly involved.³

Preoperative sputum positivity is a recognized risk factor for post-pneumonectomy empyema, which developed in 2 of our patients, both of whom were sputum positive preoperatively. One of these patients was HIV positive with a preoperative empyema.

Bronchial stump reinforcement has been advocated to prevent the postoperative development of bronchopleural fistula. However, we opted for interrupted absorbable suture approximation with only 2 patients having muscle flap reinforcement. The rationale for this included the fact that stapling devices were not available in our institution owing to their prohibitive cost. Deschamps and associates,⁷ in their review of the factors affecting the incidence of empyema and bronchopleural fistula, determined that staple closure offered a protective effect against bronchopleural fistula, albeit in a cohort that included lung resection for malignant disease. Pomerantz⁸ found that there was no difference in the incidence of bronchial stump disruption with either staple or suture closure. Blyth,⁹ from our unit, demonstrated a bronchopleural fistula rate of 1.9% using the hand-sewn technique with either absorbable or nonabsorbable suture. This rate is comparable with those of alternative strategies. Vicryl has been recommended as an acceptable suture material for bronchial stump closure.¹⁰ It was for these reasons that we adopted our current strategy for bronchial stump closure. Although our series is small, the absence of bronchopleural fistula following surgery suggests that routine reinforcement may not be necessary. Interrupted suture closure with minimal devascularization of the stump appears effective. However, long-term follow-up is required to assess its efficacy.

Our 17.4% morbidity is comparable to reported rates of 12% and 23%,^3,6 as is our cure rate of 95.6%, bearing out the efficacy of surgery in the management of MDR-TB.^3,6,11 Chemotherapy was continued for 18 months after surgery as suggested by Pomerantz and colleagues.³

The incidence of MDR-TB of 1% to 4% in South Africa compares favorably with that of developed countries.¹ Controlling this disease requires an infrastructure to monitor medical treatment and resistance patterns. In consideration of cure rates of up to 90% with acceptable morbidity and mortality rates, we support the contention that surgery may be offered as an adjunct for carefully selected patients together with an aggressive chemotherapeutic regimen.

	REFERENCES

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1. Weyer K, Groenewald P, Zwarenstein M, Lombard CJ. Tuberculosis drug resistance in the Western Cape. S Afr Med J 1995;85:499–504.[Medline]

2. Telzak EE, Sepkowitz K, Alpert P, Mannheimer S, Medard F, el-Sadr W, et al. Multidrug-resistant tuberculosis in patients without HIV infection. N Engl J Med 1995;333:907–11.[Abstract/Free Full Text]

3. Pomerantz BJ, Cleveland JC Jr, Olson HK, Pomerantz M. Pulmonary resection for multi-drug resistant tuberculosis. J Thorac Cardiovasc Surg 2001;121:448–53.[Abstract/Free Full Text]

4. Lee KS, Hwang JW, Chung MP, Kim H, Kwon OJ. Utility of CT in the evaluation of pulmonary tuberculosis in patients without AIDS. Chest 1996;110:977–84.[Abstract/Free Full Text]

5. Treasure RL, Seaworth BJ. Current role of surgery in Mycobacterium tuberculosis. Ann Thorac Surg 1995;59:1405–7.[Abstract/Free Full Text]

6. Van Leuven M, De Groot M, Shean KP, von Oppell UO, Willcox PA. Pulmonary resection as an adjunct in the treatment of multiple drug-resistant tuberculosis. Ann Thorac Surg 1997;63:1368–72.[Abstract/Free Full Text]

7. Deschamps C, Bernard A, Nichols FC III, Allen MS, Miller DL, Trastek VF, et al. Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence. Ann Thorac Surg 2001;72:243–7.[Abstract/Free Full Text]

8. Pomerantz M. Surgery for the management of Mycobacterium tuberculosis and nontuberculous mycobacterial infections of the lung. In: Shields TW, LoCicero J III, Ponn RB, editors. General thoracic surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2000:1066–75.

9. Blyth DF. Pneumonectomy for inflammatory lung disease. Eur J Cardio-thorac Surg 2000;18:429–34.[Abstract/Free Full Text]

10. Shields TW. General features of pulmonary resections. In: Shields TW, LoCicero J III, Ponn RB, editors. General thoracic surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2000:375–84.

11. Pomerantz M, Madsen L, Goble M, Iseman M. Surgical management of resistant mycobacterial tuberculosis and other mycobacterial pulmonary infections. Ann Thorac Surg 1991;52:1108–11.[Abstract]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Rishen Naidoo Anu Reddi Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Naidoo, R. Articles by Reddi, A. Search for Related Content PubMed PubMed Citation Articles by Naidoo, R. Articles by Reddi, A. Related Collections Lung - other