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Ann Thorac Surg 2006;81:2026-2030
© 2006 The Society of Thoracic Surgeons
a Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
b Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
Accepted for publication January 5, 2006.
* Address correspondence to Dr Watanabe, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan (Email: masazumi{at}sc.itc.keio.ac.jp).
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Abstract |
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METHODS: Patients with localized pulmonary lesions persisting despite extensive state-of-the art antimicrobial chemotherapy became candidates for surgical resection. Twenty-two patients who were expected to retain sufficient postoperative pulmonary function were included in this study. These patients received chemotherapy for 2 to 37 months (mean, 17). Surgical procedures were lobectomy (n = 15), segmentectomy (n = 4), and partial lung resection (n = 6). Three patients underwent bilateral resections.
RESULTS: Mycobacterium avium complex causing bronchiectasis or cavitary lesions was detected preoperatively in all 22 patients. There was no major operative morbidity or mortality. Postoperative chemotherapy was continued for 6 to 35 months. All patients were alive and well at follow-ups ranging from 6 to 164 months (median, 46). Both vital capacity and forced expiratory volume in 1 second after surgery were maintained at 89% and 84% of the preoperative values, respectively. Mycobacterium avium complex disappeared from sputum after surgery in all patients. In 1 patient, 4 months after resection of a cavitary lesion, MAC-positive sputum presumed to be from the contralateral lung lesion became negative during continuation of chemotherapy.
CONCLUSIONS: The long-term outcomes of patients operated on for MAC resistant to antimicrobial chemotherapy were excellent. For such patients, we recommend surgery before the disease becomes exceedingly advanced and nonresectable. Additionally, in extensive disease, the excision of large cavitary bacterial foci may assist the medical management of contralateral lesions.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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The surgical indications in this series of patients were (1) MAC disease refractory to multiple drug therapy, including clarithromycin, rifampicin, ethambutol, or levofloxacin; (2) localized pulmonary lesions; and (3) sufficient predictive postoperative pulmonary function.
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Results |
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The MAC infections were confirmed in all patients from cultures or MAC-polymerase chain reaction methods performed in sputum or bronchoalveolar lavage fluid before surgery, according to the criteria of the American Thoracic Society [3]. All patients had received preoperative medications for 2 to 37 months (mean, 17). Clarithromycin was administered in 18 patients, combined with a new quinolone agent such as levofloxacin, ofloxacin or sparfloxacin in 9, and with rifampicin and ethambutol in 6 patient. Single-drug therapy was performed in 3 patients because they refused combined drug therapy because of adverse effects. In 9 recent cases, drugs were selected according to the results of microdilution antimycobacterial susceptibility test.
The performance status at the time of surgery was 0 in 19 patients and 1 in 3 patients.
Medical Therapy in Our Hospital
The outline of MAC medical therapy at the outpatient clinic of internal medicine in the recent 5-year period is as follows. Patients who were found at health screenings without symptoms were followed up for 3 to 6 months at the outpatient clinic. If the findings on chest roentgenogram worsened during this period, chemotherapy was started even in asymptomatic patients. Twenty-five patients with primary MAC disease were treated in our hospital during this 5-year period. Two patients had cavitary lesions, and other patients had bronchiectatic lesions or granular shadows. Each patient was treated by rifampicin, ethambutol, clarithromycin, and levofloxacin basically. The findings of sputum culture converted from positive to negative in 20 patients within 6 months. In the other 5 patients, the sputum culture remained positive, and consequently, these 5 patients underwent pulmonary resection. (Note: 5 of these 22 patients who underwent surgery are included in this study. The other patients in this study were referred to us from other facilities after receiving initial medical therapy.)
Surgical Procedures and Pathology
Bilateral lung resections were performed in 3 patients, including sequential bilateral resections within 1 day in 1 patient (no. 4). Resections of multiple lung regions were performed in 10 patients. The primary surgical procedures consisted of lobectomy in 14, bilobectomies in 1, segmentectomy in 4, and wedge resection of the lung in 6 patients. All wedge resections were performed using stapling devices. In 1 patient with lung cancer, the tumor was excised by left lower lobectomy, and partial resection of the upper lobe was performed for MAC. Wedge resection was performed by thoracoscopy using three ports in 3 patients. Lobectomy was performed assisted by thoracoscopy in 1 patient. We limited the thoracoscopic procedures to cases with small lesions because direct palpation is important to secure enough surgical margin in MAC patients. Thoracoplasty was performed in 1 patient (no. 11), with right upper lobectomy, because of insufficient expansion of remaining middle and lower lobes and existence of large postresectional pleural space.
Microscopic findings showed granulomatous inflammation with necrosis in all cases. In all surgical specimens, MAC was confirmed by microbiological methods including polymerase chain reaction.
Postoperative Follow-Up
Patients after surgery received follow-up every 3 or 4 months. Chest roentgenographic finding was checked in every patient. Smears, cultures, and polymerase chain reaction examinations of sputum were performed in patients with sputum. There was no postoperative mortality or major complication. One patient needed home oxygen therapy soon after discharge, but it was discontinued 2 months after surgery. All patients were alive 6 to 164 months after surgery. The median survival was 46 months. The results of postoperative pulmonary function testing, which was performed at more than 6 months after surgery (range, 6 to 156 months; median, 52), were available in 18 patients and are shown together with the preoperative data in Table 2. Both vital capacity and forced expiratory volume in 1 second were reduced significantly after resection. Both values, however, were maintained at 89% and 84% of preoperative values, respectively. The results were not significantly different between patients who received lobectomy or wider resection (n = 11). The performance status after surgery was unchanged in all patients. The nutritional status of these patients was good and was not different before and after surgery.
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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Our main surgical indication is the persistence of localized lesions despite administration of multiple drugs listed earlier. Despite the administration of clarithromycin for 6 to 37 months in 18 patients who had cavitary or bronchiectatic lesions, the MAC lesions had persisted; and these organized MAC-infected lesions were uncontrollable by drug therapy alone, including clarithromycin. As recommended by several others [9, 10], we proceeded with surgical treatment early, when medical treatment appeared ineffective, before the lesions had become inoperable. In all our patients, the findings of MAC in the sputum became negative after surgery. Compared with reported postoperative conversion rates between 87% and 100% [9–13], our favorable results may attributable to the early performance of surgery.
Reports of long-term results of medical treatment for MAC pulmonary disease are very few. In the study of Kobashi and colleagues [14], the response rate of 115 patients treated according to proposed guidelines (rifampicin plus ethambutol plus streptomycin plus clarithromycin) was significantly better than that before the guidelines were established in primary MAC disease. However, poor outcomes, namely, "worsening" and "death," were still high in secondary MAC disease, at 23.1% and 10.3%. Although our follow-up is shorter, complete resection appeared to improve prognosis.
The MAC diseases were found at health maintenance examination in 10 asymptomatic patients of 22 (45%) in this series. The other 12 patients had mild symptoms. Because we performed surgery at an early stage of the disease, the rates of wedge or segmental resections were higher than reported by others. None of our patients required a pneumonectomy, and none suffered a major postoperative complication. Reported rates of major complications, such as bronchopleural fistulae and respiratory failure, associated with more invasive surgery, have been 0% to 42% [9–13]. Therefore, it appears important to avoid invasive surgery, such as pneumonectomy, if possible. Both vital capacity and forced expiratory volume in 1 second after resection were reduced slightly in this series. The performance status after surgery, however, was maintained even in lobectomy cases.
Our surgical procedures did not routinely include thoracoplasty, even after upper lobectomy, which was performed in 4 of our patients. We performed thoracoplasty in a single patient, who presented with a huge residual pleural space. Several authors [10, 13] have recommended muscle flaps to buttress the bronchial stump, and obliterate the empty space after pneumonectomy.
We performed three thoracoscopic wedge resections in this series of patients. Although it is a less invasive and technically easier procedure, resections of bronchiectatic lesions with secure surgical margins are difficult. Wedge resection was performed mainly for small cavitary lesion keeping enough margin along the bronchial wall with palpation in this series. Therefore, we limited our thoracoscopic wedge resections to one side and performed minithoracotomies on the other side in 1 patient (no. 4).
We observed 2 noteworthy patients, in whom contralateral lesions improved without organizing pulmonary changes, after resection of large cavitary lesions. We hypothesize that the resection of major bacterial foci may facilitate the chemotherapeutic management of lesions not associated with cavities or bronchiectasis.
In conclusion, we recommend that surgical treatment of MAC pulmonary lesions be performed before the disease becomes too advanced, and difficult to resect. Patients treated with a clarithromycin-containing regimen for more than 6 months for MAC pulmonary disease with cavitary or bronchiectatic lesions, even when asymptomatic, should be viewed as candidates for surgery, as it is associated with low morbidity and mortality. In extensive disease, after the resection of major cavitary bacterial foci, the contralateral lesions can be further managed postoperatively by chemotherapy.
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