HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract 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): Marc Van Leuven Ulrich O. Von Oppell Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van Leuven, M. Articles by Willcox, P. A. Search for Related Content PubMed PubMed Citation Articles by Van Leuven, M. Articles by Willcox, P. A. Related Collections Related Article

Ann Thorac Surg 1997;63:1368-1372
© 1997 The Society of Thoracic Surgeons

---

Original Article: General Thoracic

Pulmonary Resection as an Adjunct in the Treatment of Multiple Drug-Resistant Tuberculosis

Departments of Cardiothoracic Surgery and Medicine, Groote Schuur Hospital, University of Cape Town, and MDR-TB Clinic, Brooklyn Chest Hospital, Cape Town, South Africa

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
Background. Over the past decade the incidence of pulmonary disease due to drug-resistant strains of Mycobacterium tuberculosis has increased worldwide. We reviewed our local experience to clarify the benefits and risks of pulmonary resection in the management of drug-resistant strains of Mycobacterium tuberculosis.

Methods. A retrospective review was performed of 62 patients undergoing pulmonary resection for drug-resistant strains of Mycobacterium tuberculosis between January 1990 and November 1995.

Results. Fifty-three percent were men and 47% women with an average age of 34 years (range, 16 to 72 years). There was one postoperative death, for a perioperative (30-day) mortality of 1.6%. Sixteen complications occurred in 14 patients for an overall morbidity of 23%. Eighteen of 24 patients (75%) who were persistently sputum positive at the time of operation immediately converted to a negative sputum smear and culture. For all patients who were sputum negative after operation 80% remain relapse-free by actuarial analysis.

Conclusions. We believe that operation plays an important ancillary role in the treatment of drug-resistant strains of Mycobacterium tuberculosis. The operation can be performed with acceptable morbidity and mortality and must be combined with appropriate and well-monitored pre- and postoperative antituberculous drug therapy.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
See alos page 1372.

Over the past decade the incidence of pulmonary disease due to drug-resistant strains of Mycobacterium tuberculosis (MDR-TB) has increased worldwide. This has been primarily through the effects of inadequate first course therapy, poor patient compliance, inadequate monitoring, and the increasing prevalence of human immunodeficiency virus infection [1, 2]. The Western Cape region of South Africa has a particularly high prevalence of tuberculosis including drug-resistant varieties [3].

Drug therapy for fully sensitive strains of M tuberculosis will result in clinical cure in more than 95% of patients under trial conditions. In contrast, medical treatment for MDR-TB is often disappointing with nonconversion or relapses occurring in up to 50% of patients with 40% to 50% of these patients succumbing from progressive disease within 10 to 15 years [4]. Recent studies have shown the benefit of operation as an ancillary treatment modality in the management of MDR-TB [5]. The favorable outcome of a combination of drug therapy and surgery in selected patients with reasonably localized disease has been reported by Iseman [6] and Pomerantz [7] and their colleagues. Accordingly we have reviewed our local experience to clarify indications and expected outcome for operation in these patients.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
We retrospectively reviewed the clinic and hospital records of all patients undergoing pulmonary resection for tuberculosis at Groote Schuur Hospital, Cape Town, between January 1990 and November 1995. During this time we performed pulmonary resections on 214 patients with lung destruction due to M tuberculosis and of this group 62 were caused by strains resistant to at least isoniazid and rifampicin (MDR-TB). Patients were selected for operation by consensus opinion by a medical (P.A.W.) and surgical (M.D.G.) specialist based on personal experiences in treating pulmonary tuberculosis.

Preoperative investigations consisted of chest roentgenogram, simple spirometry, electrocardiogram, and routine blood analysis. In most cases the extent of lung resection was based on the conventional chest radiograph. Where doubt existed about the extent of local disease or presence of bilateral disease, computed tomography of the chest was performed to delineate areas of lung damage. Where there was concern of the functional capacity of remaining lung a quantitative perfusion scan was used to determine the necessity of a pneumonectomy over a lobectomy. To facilitate analysis a classification system was used to divide the chest roentgenogram into six zones and grade them (grades 1 to 5) on changes associated with acute or old tuberculosis as follows: (1) gross and extensive cavitation: a single cavity larger than 2 cm/three or more cavities of any size; (2) minimal cavitation: cavitation smaller than 2 cm and less than three cavities; (3) nodules: rounded opacities varying in size from 0.5 to 2 cm; (4) fibrosis: areas of chronic atelectasis or scaring; and (5) bullae: thin-walled bullae usually singular.

All operations were performed using a double-lumen endotracheal tube through serratus muscle-sparing posterolateral thoracotomies. Areas of gross cavitation and destruction were mobilized using an extrapleural approach to avoid contamination of the pleural space. All pneumonectomy stumps were stapled with lobectomy and segmentectomy bronchial stumps being oversewn with interrupted polyglactin sutures. No specific preemptive techniques such as muscle flaps or thoracoplasty was used to protect the bronchial stump during the initial operation. A sample of resected lung tissue was sent for tuberculosis culture, and routine histopathology including Ziehl-Nielsen staining.

Postoperative follow-up was conducted at a dedicated MDR-TB clinic where monthly sputum cultures were done until there were three consecutive negative cultures. Thereafter, sputum smear, culture, and a chest radiograph were performed every 3 months until completion of therapy. After termination of treatment the patient was reviewed every 6 months for 2 years, and if disease-free, discharged from the MDR-TB clinic.

Actuarial analysis of the relapse-free interval was performed using the Kalpan-Meier method using the SPSS statistical package (SPSS Inc, Chicago, IL).

	Results

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
Patient Characteristics
Of the 62 patients 33 (53%) were men and 29 (47%) women. There were 48 (77%) mixed race, 10 (16%) black, and 4 (7%) white patients, with an average age of 34 years (range, 16 to 72 years). Only 1 patient was diabetic and no patients were human immunodeficiency virus positive at the time of operation. The indication for lung resection of each patient is displayed in Table 1. Often, more than one indication was present in the same patient. During the preoperative evaluation 25 patients (40%) had a quantitative perfusion scan and 9 (15%) had computed tomography with overlap in 8 patients. The extent of lung resection is recorded in Table 2.

	Surgical Morbidity and Mortality

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

Sixteen complications occurred in 14 patients for an overall morbidity of 23%. These are: postoperative hemorrhage, 5 patients (8%); postpneumonectomy empyema, 4 (6%); wound infection, 2 (3%); pneumonectomy stump fistula, 2 (3%); postpericardiotomy syndrome, 1 (2%); respiratory failure, 1 (2%); and space problem, 1 patient (2%). Hemorrhage requiring reexploration was the most common complication that occurred in 5 patients. No septic complications developed in patients who were reexplored. Postpneumonectomy empyema occurred in 4 patients (3 left, 1 right); in 2 it was associated with concomitant stump dehiscence (1 left, 1 right). Of the empyemas not associated with fistulas, 1 patient had active MDR-TB cultured in the contents and in the remaining patient no overt cause or organism could be identified. All patients were initially treated with closed drainage before the creation of an Eloesser flap. Postpericardiotomy syndrome was diagnosed in 1 patient in whom the pericardium had been opened to facilitate vascular control. A transient space problem occurred in 1 patient who underwent a right upper and middle lobectomy with no untoward long-term sequelae.

	Results of Operation

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
A flow diagram of the overall results of operation is displayed in Figure 1. Six of the 24 (25%) patients who were still sputum positive at the time of operation (group A of Table 1) failed to convert after operation. However, 3 patients of this group of "early surgical failures," converted subsequently, on medical treatment and of these patients, 2 are now off medication and disease-free, and one is still on treatment with sputum smears and cultures remaining negative. Outcome in the other 3 patients was less favorable, with 2 succumbing to progressive disease. The remaining smear-positive patient declined a potentially curative completion pneumonectomy. Of note each patient who did not convert postoperatively had active M tuberculosis bacilli in the resection specimen, making the resection appropriate, but possibly incomplete because of residual ipsilateral or contralateral disease. Figure 2 relates the success of sputum conversion to the type of procedure performed in 24 group A patients. It would appear that a limited resection carries a greater risk of failure to convert after operation. Compared with patients who successfully converted with operation, there was no radiologic pattern of residual damaged associated with failure to sputum convert.

View larger version (21K): [in this window] [in a new window]   Fig 1. . Results of operation for 62 patients undergoing pulmonary resection for drug-resistant strains of Mycobacterium tuberculosis.

View larger version (15K): [in this window] [in a new window]   Fig 2. . Success of pulmonary resection in converting sputum in 24 drug-resistant strains of Mycobacterium tuberculosis sputum-positive patients related to the type of resection performed.

View larger version (13K): [in this window] [in a new window]   Fig 3. . Actuarial relapse rate for patients sputum negative after pulmonary resection. (AFB = acid-fast bacilli.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
The rationale for considering operation is to excise specific areas where M tuberculosis bacilli can evade the effects of host defenses and antibiotic therapy. Historically and intuitively these have been considered to be areas of gross cavitation where the local environment provides a "firewall" of protection. Through ablation of these areas one would presumably unshield the remaining bacilli and make them amenable to cure by chemotherapy. The majority of patients with MDR-TB display bilateral radiologic changes of varying degrees during some stage of their illness. In most cases one can make a reasonable prediction by means of plain chest roentgenogram which lung part contains the bacterial reservoir. In our series only 15% of patients had computed tomography performed where the anatomic location or presence of other areas of gross cavitation was in doubt. Whether the use of enhanced imaging techniques can improve the results of ancillary operation for MDR-TB remains a matter for further investigation.

Operation for MDR-TB is generally accepted as an ancillary treatment modality for selected MDR patients [8, 9]. The criteria for selection of patients who may benefit from operation remain vague and enigmatic, certainly to people unfamiliar with general treatment of pulmonary tuberculosis. One can distinguish between two main subsets of patients in whom operation may be indicated. The first is patients who fail to convert despite an adequate drug regimen (group A in Table 1). Rather arbitrarily we can define an adequate drug regimen as one that contains at least four drugs to which the resistant M tuberculosis strain is sensitive and from which at least three were not used previously [5]. We believe that the length of treatment should not exceed 6 months before failure is conceded and operation considered. The second group includes patients that have already in the course of treatment of MDR-TB converted to a sputum-negative status. Here, operation is preemptive to hopefully prevent a relapse with increased drug resistance and less room for adequate control with further drug therapy. In this group the indication for operation is less clearcut and subject to controversy. As yet no controlled study exists proving that the addition of operation favors long-term control and prevention of relapse over drug therapy alone. This group is not homogeneous and different personal approaches to the problem account for differences in categorizing of the patients. We divided this group into three groups: (1) patients who were likely to relapse, given a previous history of relapse, especially when on MDR drug treatment (group B in Table 1); (2) patients with a high level of drug resistance, ie, resistance to four or more drugs, especially when also resistant to an aminoglycoside (group C in Table 1); and finally (3) patients not falling into the previous categories, but in whom the likelihood of relapse was gauged by composite indications of radiology, compliance, and risk to the patient if subsequent relapse were to occur (group D in Table 1). This last category represents the most controversial indication, and certainly part of this group might do well without operation.

Unfortunately there is no diagnostic tool that tells us with certainty where the reservoir of resistant bacilli is located. On review of our data we found no pattern that could accurately predict whether success or failure on the basis of radiologic changes. No gross cavitation was left behind in any patient who did not convert after operation. Possibly the disease reservoir may lie in residual nodules, bullae, microcavitation, or even fibrosis. We found no correlation between the amount of radiologic residual disease and the failure to convert after operation or the ability to subsequently convert on further medical therapy. Our experience of a higher percentage of nonconversion with lobectomies and segmentectomies as compared to pneumonectomies suggest that there may be merit in choosing a more radical procedure over a lesser resection where doubt exists over complete excision of bacterial reservoirs. This approach may result in more space-related problems as in the case of extended lobectomies or postpneumonectomy complications.

Identification of risk factors predisposing to relapse is difficult. Too short postoperative treatment course can be one factor as evident in 2 of 6 patients in the current study who relapsed. The patients had inadequate courses ranging from 0 months (a preoperative nonconverter who defaulted for medical therapy after operation), to 4 months (treatment stopped by other clinic without taking date of operation into account). Patients who by our judgment had too short postoperative treatment courses converted on resumption of medical therapy and are currently disease free. On the other hand, 2 patients relapsed while still on treatment, the cause of the relapse being obscure. Reinfection always remains a continuing possibility, especially in areas with a high prevalence of pulmonary tuberculosis. In 1 patient relapsing after more than 2 years the organism was fully drug sensitive, raising the probability of reinfection. This patient converted on first-line tuberculosis drugs, and is still on medication. Finally a resection can be incomplete if small foci of drug-sheltered bacilli remain, only to reactivate at a later stage, as might be the case in residual ipsilateral disease or bilateral disease. In our series, to hypothesize that a more extensive resection is indicated would be difficult as 4 patients of the 6 who relapsed had undergone a pneumonectomy. The serious consequences of relapse are exemplified in the 3 patients who failed to convert after relapse, in that 1 died of progressive disease and the other 2 are still alive but remain on medication.

The length of postoperative drug therapy remains controversial. Operation may ablate the major reservoir of the bacilli, but the "cure" resides with the completeness of the antibiotic course. In addition, the initial treatment is likely to have the highest probability of success. Balanced against this is the expense involved in administering and monitoring third-line drug regimens. Although it appears prudent to continue drug therapy for 18 to 24 months in patients as suggested by Iseman and colleagues [6], it might be overzealous to generalize this concept. Our approach is a "tailored" plan taking into account residual disease, sputum status at operation, microbiology and histopathology of the resection specimen, and the initial indication for operation to formulate a logical length of postresection chemotherapy. The importance of continued monitoring of patients cannot be understated as 2 patients relapsed from failure of adherence to prescribed regimens after initial sputum conversion accounting for 33% of late failures.

The addition of operation in a treatment plan is only advisable if the procedures can be carried out with a low morbidity and mortality. Operation for inflammatory lung disease involves a subset of techniques that are not commonly practiced and should take place in a unit specializing in such procedures. The procedures can be carried out with a high probability of success and an acceptable mortality (1.6% in our group). General morbidity figures appear to be quite high (23%), but only 4 patients (6.5%) with postpneumonectomy empyema required prolonged admission and a further operation. We have not used muscle or omental flaps for bronchial stump reinforcement as preventive strategy as suggested by other researchers [9, 10] for certain circumstances. In our series the use of careful, nondevascularizing dissection and routine stapling of main bronchi resulted in only two fistulas (3%).

We conclude from our observations that pulmonary resection can play an important ancillary role in the treatment of MDR-TB. This operation can be performed safely in specialized units with acceptable morbidity and mortality and must be combined with appropriate and well-monitored pre- and postoperative antituberculous drug therapy.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 
Address reprint requests to Dr De Groot, Department of Cardiothoracic Surgery, University of Cape Town, Medical School, Observatory 7925, Cape Town, South Africa.

	References

Top Footnotes Abstract Introduction Material and Methods Results Surgical Morbidity and Mortality Results of Operation Comment References

 

1. O'Brien RJ. Drug-resistant tuberculosis: etiology, management and prevention. Semin Respir Infect 1994;9:104–12.[Medline]
2. Iseman M. Evolution of drug-resistant tuberculosis: a tale of two species. Proc Natl Acad Sci 1994;91:2428–9.[Abstract/Free Full Text]
3. Weyer K, Groenewald P, Zwarenstein M, Lombard CJ. Tuberculosis drug resistance in the Western Cape. S Afr Med J 1995;85:499–504.[Medline]
4. Goble M, Iseman M, Madsen L, Waite D, Ackerson L, Horsburgh R. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampacin. N Engl J Med 1993;328:527–32.[Abstract/Free Full Text]
5. Iseman M. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993;329:784–91.[Free Full Text]
6. Iseman MD, Madsen L, Goble M, Pomerantz M. Surgical intervention in the treatment of pulmonary disease caused by drug-resistant Mycobacterium tuberculosis. Am Rev Respir Dis 1990;141:623–5.[Medline]
7. 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]
8. Treasure RL, Seaworth BJ. Current role of surgery in Mycobacterium tuberculosis. Ann Thorac Surg 1995;59:1405–7.[Abstract/Free Full Text]
9. Rizzi A, Rocco G, Robustellini M, Rossi G, Della Pona C, Massera F. Results of surgical management of tuberculosis: experience in 206 patients undergoing operation. Ann Thorac Surg 1995;59:896–900.[Abstract/Free Full Text]
10. Brown J, Pomerantz M. Extrapleural pneumonectomy for tuberculosis. Chest Surg Clin N Am 1995;5:289–96.[Medline]

This article has been cited by other articles:

				H. Wang, H. Lin, and G. Jiang Pulmonary Resection in the Treatment of Multidrug-Resistant Tuberculosis: A Retrospective Study of 56 Cases Ann. Thorac. Surg., November 1, 2008; 86(5): 1640 - 1645. [Abstract] [Full Text] [PDF]

				L P. Ormerod Role of surgery in pulmonary multidrug-resistant tuberculosis Thorax, May 1, 2007; 62(5): 377 - 377. [Full Text] [PDF]

				J. G Somocurcio, A. Sotomayor, S. Shin, S. Portilla, M. Valcarcel, D. Guerra, and J. Furin Surgery for patients with drug-resistant tuberculosis: report of 121 cases receiving community-based treatment in Lima, Peru Thorax, May 1, 2007; 62(5): 416 - 421. [Abstract] [Full Text] [PDF]

				R. Naidoo Active Pulmonary Tuberculosis: Experience with Resection in 106 Cases Asian Cardiovasc Thorac Ann, April 1, 2007; 15(2): 134 - 138. [Abstract] [Full Text] [PDF]

				H. J. Kim, C. H. Kang, Y. T. Kim, S-W. Sung, J. H. Kim, S. M. Lee, C-G. Yoo, C-T. Lee, Y. W. Kim, S. K. Han, et al. Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis Eur. Respir. J., September 1, 2006; 28(3): 576 - 580. [Abstract] [Full Text] [PDF]

				Adjuvant resectional surgery improves cure rates in multidrug-resistant tuberculosis. J. Thorac. Cardiovasc. Surg., March 1, 2006; 131(3): 693 - 696.

				R. Naidoo and A. Reddi Lung Resection for Multidrug-Resistant Tuberculosis Asian Cardiovasc Thorac Ann, June 1, 2005; 13(2): 172 - 174. [Abstract] [Full Text] [PDF]

				Y. Shiraishi, Y. Nakajima, N. Katsuragi, M. Kurai, and N. Takahashi Resectional surgery combined with chemotherapy remains the treatment of choice for multidrug-resistant tuberculosis J. Thorac. Cardiovasc. Surg., October 1, 2004; 128(4): 523 - 528. [Abstract] [Full Text] [PDF]

				D Shitrit, D Bendayan, M Saute, and M R Kramer Multidrug resistant tuberculosis following lung transplantation: treatment with pulmonary resection Thorax, January 1, 2004; 59(1): 79 - 80. [Abstract] [Full Text] [PDF]

				G. Kaplan, F. A. Post, A. L. Moreira, H. Wainwright, B. N. Kreiswirth, M. Tanverdi, B. Mathema, S. V. Ramaswamy, G. Walther, L. M. Steyn, et al. Mycobacterium tuberculosis Growth at the Cavity Surface: a Microenvironment with Failed Immunity Infect. Immun., December 1, 2003; 71(12): 7099 - 7108. [Abstract] [Full Text] [PDF]

				J. Timm, F. A. Post, L.-G. Bekker, G. B. Walther, H. C. Wainwright, R. Manganelli, W.-T. Chan, L. Tsenova, B. Gold, I. Smith, et al. Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients PNAS, November 25, 2003; 100(24): 14321 - 14326. [Abstract] [Full Text] [PDF]

				R. Loddenkemper, D. Sagebiel, and A. Brendel Strategies against multidrug-resistant tuberculosis Eur. Respir. J., July 1, 2002; 20(36_suppl): 66S - 77s. [Abstract] [Full Text] [PDF]

				R. Souilamas, M. Riquet, F. Le Pimpec Barthes, A. Chehab, A. Capuani, and E. Faure Surgical treatment of active and sequelar forms of pulmonary tuberculosis Ann. Thorac. Surg., February 1, 2001; 71(2): 443 - 447. [Abstract] [Full Text] [PDF]

				D. F. Blyth Pneumonectomy for inflammatory lung disease Eur. J. Cardiothorac. Surg., October 1, 2000; 18(4): 429 - 434. [Abstract] [Full Text] [PDF]

				S.-W. Sung, C. H. Kang, Y. T. Kim, S. K. Han, Y.-S. Shim, and J. H. Kim Surgery increased the chance of cure in multi-drug resistant pulmonary tuberculosis Eur. J. Cardiothorac. Surg., August 1, 1999; 16(2): 187 - 193. [Abstract] [Full Text] [PDF]

This Article Abstract 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): Marc Van Leuven Ulrich O. Von Oppell Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van Leuven, M. Articles by Willcox, P. A. Search for Related Content PubMed PubMed Citation Articles by Van Leuven, M. Articles by Willcox, P. A. Related Collections Related Article