- Email: [email protected]
SURGICAL EXPERIENCE IN THE MANAGEMENT OF ATYPICAL MYCOBACTERIAL INFECTIONS
SURGICAL EXPERIENCE I N THE OF ATYPICAL MYCOBACTERIAL Sam W. Law, M.D.* (by invitation),
INFECTIONS
Daniel E. Jenkins,
Irving Chofnas, M.D.***
David Bahar, M.D.**** (by invitation),
(by invitation),
MANAGEMENT
(by invitation),
(by
invitation),
Frances Whit comb,
H. T. Barkley, M.D.,******
Michael E. De Bakey, M.D.,*******
M.D.**
Houston,
M.S.*****
and Texas
T
HE atypical or unclassified Mycobacteria are now widely recognized and accepted as the causative agents of granulomatous pulmonary disease in humans. The pulmonary disease caused by these atypical acid-fast organisms is similar, both clinically and roentgenographically, to disease caused by Mycobacterium tuberculosis. Identification of the atypical mycobacterial infection is primarily dependent upon the astuteness of the bacteriologist, and may not occur until after the patient has been hospitalized and treated from 4 to 6 weeks as having a typical tuberculous infection. The subsequent management and evaluation of response to therapy is, therefore, frequently governed by guide lines established for the treatment of disease caused by M. tuberculosis. However, increasing experience with disease caused by the atypical Mycobacteria suggests that there are sufficient differentiating clinical features to justify estab lishing specific treatment programs and evaluation criteria. The frequent observation of in vitro resistance to the antituberculous chemotherapeutic drugs by the atypical Mycobacteria, either on pre-treatment studies or emerging early in the course of treatment, has been a source of significant concern. Similarly, the response of these patients to drug therapy may be slow or absent. In 180 patients with atypical mycobacterial pulmonary disease, principally Group I I I infections, Corpe and Liang 1 observed a sputum Prom the Cora and Webb Mading Department of Surgery, the Departments of Medicine and Microbiology, Baylor University College of Medicine, the Veterans Administration Hospital, and the Pulmonary Disease Section of Jefferson Davis Hospital, Houston, Texas. Supported in part by the U. S. Public Health Service (E-3373). Read a t the Forty-third Annual Meeting of The American Association for Thoracic Sur gery a t Houston, Texas, April 8-10, 1963. •Chief, Surgical Service, Veterans Administration Hospital. ♦•Professor of Medicine, Baylor University College of Medicine. •••Chief, Pulmonary Disease Section, Veterans Administration Hospital. ••••Assistant Director, Tuberculosis Division, Jefferson Davis Hospital. •••••Research Bacteriologist, Pulmonary Disease Laboratory, Veterans Administration Hospital. ••••••Chief of Surgery, Tuberculosis Division, Jefferson Davis Hospital. •••••••Professor and Chairman, Cora and Webb Mading Department of Surgery, Baylor University College of Medicine. 689
690
LAW E T AL.
J. Thoracic and Cardiovas. Surg.
conversion rate of 22 per cent after 6 months of conventional antitubereulous chemotherapy. In the same hospital there was a sputum conversion rate of 90 per cent after 6 months of similar therapy in patients with disease caused by M. tuberculosis. Bahar, Chofnas, and Jenkins 2 have reported a sputum con version rate of 60 per cent after 6 months of drug therapy in 73 patients with disease due to Mycobacterium kansasii, or Group I organisms. This delayed response to medical treatment and the frequent presence of drug resistance have caused serious concern about the safety of surgical inter vention in atypical mycobacterial disease. However, these same factors signifi cantly increase the potential usefulness of resective surgery in the control of this disease. This report will evaluate the safety and effectiveness of surgery in the management of pulmonary disease caused by atypical Mycobacteria from the extensive experience in this center, principally with Group I organisms, and from the experience recorded by others. 24 22 20 18 16
H I Jeff. Davis
rjV.A.H. ^^
-12 «10 « 8 a- 6 4 2 20-29 30-39 40-49 50-59 60-69 Age in Years Pig. 1.—Age of patients. MATERIAL
In the Baylor Affiliated Hospitals, from June 3, 1952, through June 30, 1962, there have been 68 elective thoracic surgical procedures performed on 64 patients with infections caused by atypical Mycobacteria. Each patient has had clinical and roentgenographic evidence of granulomatous pulmonary disease, and each operation was designed to convert positive sputum or to remove a major disease residual. No patient is included who has had an incidental single isolation of atypical Mycobacteria, and no patient exhibiting a mixed infection, with isolation of both atypical Mycobacteria and M. tuberculosis, is included. The 64 patients have ranged in age from 29 to 68 years (Fig. 1); 57 were Caucasian and 7 were Negro; 61 were male and 3 were female. Forty-four of the operations were performed on 43 patients at the Veterans Administration Hospital, and 24 operations were performed on 21 patients through the Tuber culosis Division of the Jefferson Davis Hospital, a city-county institution. This may partially explain the age and sex distribution, but the high incidence of this disease in the older white male has been previously noted.2"'1G
Vol. 46. No. 5 November, 1963
ATYPICAL MYCOBACTEKIAL I N F E C T I O N S
691
On admission to the hospital, the pulmonary disease present in these pa tients was classified3 as minimal in 3 patients, moderately advanced in 35 patients, 6 of which were bilateral, and far advanced in 26 patients, 19 of which were bilateral (Table I ) . TABLE I. |
E X T E N T OP D I S E A S E ON ADMISSION
UNILATERAL
|
Minimal 3 Moderately advanced 29* F a r advanced 7t Totals 39 •Three complications occurred (or encountered). tTwo complications occurred.
BILATERAL
6 19* 25
|
TOTALS
3 35 26 64
Bacteriology.—The criteria and classification of Runyon 4 have been used in the identification of the atypical Mycobacteria in this laboratory throughout the period of this report. The interchange of cultures with Dr. Runyon 's labora tory has been sufficient to establish unequivocally the uniformity of identifica tion and classification. In 56 of the patients included in this report, the causative organisms were Runyon's Group I or photochromogens, now designated Mycobacterium kansasii; in 2 patients the causative organisms were Runyon's Group II, or skotochromogens; in 5 patients the organisms were Runyon's Group III, or non-chromogens; and in one patient the organisms were Runyon's Group IV, or rapid growers. Al though this report includes every patient with atypical mycobacterial pulmonary disease who underwent surgery in this center, the major interest is in the extensive experience with pulmonary disease caused by Mycobacterium kansasii, or Group I organisms. The same species of acid-fast organisms was found throughout the course of the disease in each patient, and the organisms found in the positive surgical specimens were always the same as had previously been isolated from the sputum. A positive sputum culture had been obtained during the 90 days pre ceding the surgical procedure in 47 of the 68 patients (69 per cent). Atypical acid-fast organisms were found on smear or culture or both in 47 of the 60 surgical specimens (78 per cent). Thus, viable atypical acid-fast organisms were recovered from the sputum preoperatively or from the surgical specimen in 58 of the 68 operations (85 per cent). In vitro antituberculous drug susceptibility studies were performed re peatedly on the organisms obtained from each patient. These studies have been performed and interpreted according to the Laboratory Methods of the Veterans Administration-Armed Forces Cooperative Study on the Chemotherapy of Tuberculosis. A previous report 2 " has discussed the problems of natural re sistance and rapidly emerging resistance of these atypical organisms to the individual antituberculous drugs. In the retrospective study of this group of patients, the last available preoperative susceptibility tests have been used to
LAW ET AL.
692
J. Thoracic and Cardiovas. Surg.
place each patient in one of three arbitrary groups, based on the estimated effectiveness of the chemotherapeutie program: "effective chemotherapy," pa tients whose organisms were susceptible to two or more of the drugs being administered; "partially effective chemotherapy," patients whose organisms demonstrated resistance to some drags, but the patient was receiving one drug to which the organisms were susceptible; and "ineffective chemotherapy," pa tients whose organisms were resistant to all of the antituberculous drugs which the patient was receiving, or the patient received no drugs preoperatively. (See Table V.)
Fig. 2.—Duration of preoperative chemotherapy. MEDICAL TREATMENT
The medical treatment of these patients has consisted of hospitalization, a limited but confining rest program, and antimicrobial drugs. 2 The majority of the patients have received isoniazid, 5 to 10 mg. of body weight per day, in combination with sodium para-aminosalicylate, 15 Gm. daily, or streptomycin, 1 Gm. twice weekly. Some patients have received, in addition, courses of kanamyein, cycloserine, pyrazinamide, a sulfonamide, or tetracycline. There has not been a uniform policy of additional drug coverage in the preoperative period. The duration of preoperative chemotherapy in these patients has varied from none in 5 patients to over 5 years in 2 patients (Fig. 2). The small number of patients and the wide variability in type and extent of disease encountered in this group of patients prevents identification of an optimum duration of preoperative chemotherapy and emphasizes the necessity of individualizing each patient's treatment program. Preoperative bronchoscopy has been performed routinely. With the excep tion of the 2 patients with total destruction of a lung requiring pneumonectomy, endobronchial disease has not been encountered. Since it has not been customary
Vol. 46 No S
ATYPICAL MYCOBACTERIAL I N F E C T I O N S
November, 1963
fiq3
U J O
to bronchoscope these patients prior to initiation of chemotherapy, the possible role of endobronchitis in untreated disease due to the atypical Myeobacteria cannot be evaluated. SURGICAL TREATMENT
Every patient considered for surgery has been evaluated by a MedicalSurgical Conference. Each patient for whom surgery was recommended had demonstrated some response to treatment with roentgenographic evidence of either clearing or stability of the pulmonary lesion. The primary indications for surgery have been failure to convert sputum, the persistence of a cavity beyond the third month of treatment, unresolved large nodular or caseous re sidual, and destroyed lung. Other factors considered in the decision to recom mend surgery have been the demonstration of resistance in drug susceptibility studies, the younger age group, and the presence of a socioeconomic background which would make prolonged cooperation in treatment doubtful. Excisional surgery has been recommended in every patient with sufficient pulmonary reserve to tolerate resection. The extent of each resection performed has been based on the surgeon's evaluation of the disease found at thoracotomy, without consideration of the patient's sputum status or drug susceptibility studies. The guiding principle has been the maximum preservation of function ing pulmonary tissue consistent with adequate removal of the disease. Segmental resection has been used when the major disease focus could be removed through a clean intersegmental plane. The term "lobectomy plus" includes bi-lobectomy as well as lobectomy plus segmentectomy. The proportionate number of each type of operative procedure performed in each year of this study has remained relatively uniform (Table I I ) . The collapse procedures include one thoracoplasty and seven extraperiosteal Ivalon plombages. In 2 patients the plombage was a planned pre-resection col lapse. In the remaining 6 patients, collapse was selected as the only feasible surgical procedure for a patient in whom the disease could not be controlled with medical therapy alone, but with a pulmonary reserve too limited to permit excisional surgery. Multiple pi-ocedures were performed in 3 patients. In each instance the sequence of surgical attack was planned at the initial therapy conference as TABLE I I .
11952 Collapse Wedge Segmentectomy Lobectomy Lobectomy plus Pneumonectomy Totals
1953 1954
1955
SURGICAL
1956
1
1
1
2 1
1
It 4
1 It 1 3
2 2
PROCEDURES*
1957 1958 2 2 1 3 2 6 1 It 8
10
1959 1 1 4 6 It 13
1960 1961 | 1962 1 1 2t 4 5t 1 11
2 5t 1 10
4t
5
TOTALS
8 3 21 28 6 2 68
•The proportionate number of each type of operative procedure performed during each year of this study has remained relatively uniform. The term "lobectomy plus" includes biIobectomy and lobectomy plus segmentectomy. tOne complication occurred.
J. Thoracic and Cardiovas. Surg.
LAW E T AL.
694
the ideal management of extensive disease. One patient had a left extraperiosteal plombage followed by left upper lobectomy, another patient had a left apical-posterior segmentectomy followed by right upper lobectomy, and one patient had a left extraperiosteal plombage, a right apical-posterior segmenjtectomy, and then a left upper lobectomy. The operative procedures and the postoperative care of the patients have been performed by residents under the supervision of the teaching staff. COMPLICATIONS OF SURGERY
There has been no operative mortality in this group of patients. Nineteen complications have occurred in the performance of 68 operative procedures, a total complication rate of 28 per cent (Table I I I ) . TABLE I I I .
Resections—60 Bronchopleural Delayed expansion Operative spread Wound infection Serum hepatitis Subclavian artery injury Intestinal obstruction Cardiac arrhythmia Total Collapse—8 Infection of plombage Postoperative psychosis Total
COMPLICATIONS OF SURGERY
fistula
4 4 3 2 1 1 1 1 17 1 1 2
6.6 6.6 5.0 3.3 1.6 1.6 1.6 1.6 28.8% 12.5 12.5 25%
In comparing this series of patients with other reports, it is evident that some authors have restricted their attention to those complications considered to be directly related to the activity of the acid-fast disease, the drug resistance of the organisms, or compromising successful control of the disease. For this reason, this artificial distinction will be made here, and primary attention will be directed to eight of the complications. These include 4 bronchopleural fistulas, 3 instances of disease spread, and a pyogenic infection of an extraperiosteal Ivalon plombage (11.7 per cent). Four bronchopleural fistulas have occurred following the 60 resective pro cedures, an incidence of 6.6 per cent. Two fistulas followed lobectomy, and one developed after a right upper lobectomy and superior segmentectomy. Tailoring thoracoplasties have controlled the fistulas, and the patients remain sputum negative. The fourth fistula developed after right apical-posterior segmentectomy. Because of rapid subsidence of systemic signs and of poor gen eral condition in a psychotic patient who will require prolonged hospitalization, a course of observation was elected. The patient continues to improve, the pleural pocket is decreasing in size, and the sputum is negative. A thoracoplasty will probably be required eventually.
Vol. 46, No. 5 November, 1963
A T Y P I C A L MYCOBACTERIAL I N F E C T I O N S
695 vo °
Disease spread or reactivation occurred postoperatively in 3 patients. In one patient, during the first month after bi-lobectomy, roentgenographic changes appeared but cleared rapidly on continued drug therapy. The patient has not had positive sputum since operation. Disease spread occurred on the contralateral side following bi-lobectomy in a patient with Group I I I or non-chromogenic organisms, who has continued to have positive sputum. A cavity in the left lung of a third patient reopened after right pneumonectomy and he con tinued sputum positive until his death 4 years later. The last 2 patients will be mentioned again as the only 2 patients in this group whose disease has not been controlled by the medical-surgical program. The infection of the Ivalon plombage (the procedure had been performed in this patient because of persistence of cavity despite sputum negativity for 13 months) required conversion to a thoracoplasty on the sixteenth postopera tive day. The staphylococcal infection was controlled with difficulty, but the subscapular space closed, and the patient remained sputum negative. In relating the operative procedures and complications to the species of atypical organism, it is noted that 60 operative procedures were performed in 56 patients with Mycobact&rium kansasii, Group I, or photochromogenic or ganisms (Table I V ) . All of the complications have occurred in this group ex cept those mentioned below. There have been two surgical procedures per formed in patients with Group II, or skotochromogenic organisms, a lobectomy and a pneumonectomy, each performed without complication. In the 5 patients with Group III, non-chromogens or Battey strains, there has been one plombage without complication, one segmentectomy followed by delayed expansion, one lobectomy which was followed by a wound infection, and two "lobectomy plus" procedures, one of which was followed by a disease spread. Thus, in the 5 pa tients with Group I I I infections, there were three complications, only one of which was related to the acid-fast disease (20 per cent). The patient with Group IV organisms underwent lobectomy uneventfully. The principal complications encountered in this series of patients are pre sented in Table V in relation to the patient's sputum status at surgery, and the estimated effectiveness of the chemotherapy administered preoperatively. The high incidence of complications in the "lobectomy plus" and "pneumonec-
TABLE
IV.
BACTERIOLOGIC CLASSIFICATION |
GROUP I
|
GROUP II
|
AND
SURGICAL
GROUP
in
|
COMPLICATIONS* GROUP IV
|
TOTALS
1 8 Collapse 7t 3 Wedge 3 1 21 Segmentecotmy 201 1 1 1 28 Lobectomy 25} 6 Lobectomy plus 2t 4* 1 2 Pneumonectomy It 1 60 2 5 68 Totals •All of the principal complications encountered occurred in the patients with Group I infections, except for one instance of disease spread which occurred in a patient with Group III infection following bi-lobectomy. tOne complication occurred. {Two complications occurred.
696
LAW ET AL.
J. Thoracic and Cardiovas. Surg.
tomy" groups is probably related to efforts to control extensive disease. In comparing the "segmentectomy" and "lobectomy" groups, it may be seen that the complications encountered were not directly related to sputum positivity or drug resistance of the organisms. The records of this group of patients have been repeatedly analyzed in relation to the possible protective role of preoperative sputum negativity or bacterial drug susceptibility, in relation to the preoperative roentgenographic response of the patient's disease, and in relation to the adequacy and length of preoperative drug therapy. It has not been possible to correlate any of these factors with the occurrence of surgical complications, or the patient's response to surgery. It has become increasingly evident that carefully planned and skillfully performed surgery with meticulous postopera tive care are of the utmost importance in the successful conduct of these pa tients through an operation. TABLE V.
CHEMOTHERAPY EFFECTIVENESS AND SURGICAL COMPLICATIONS* S P U T U M POSITIVE
S P U T U M NEGATIVE EFFECTIVE
PARTIALLY EFFECTIVE
INEFFEC TIVE
EFFECTIVE
PARTIALLY EFFECTIVE
INEFFEC TIVE
TOTALS
8 5 3 1 2 21 2 9t 4 1 3 2 28 13 1 5 4 2t 3t 6 2* 4t 2 1 It 34 68 3 10 7 11 Totals 3 ♦The principal complications encountered have not been easily correlated with the patient's sputum status at the time of surgery, or with an arbitrary estimate of the effectiveness of the chemotherapeutic program. tOne complication occurred. JTwo complications occurred. Collapse Wedge Segmentectomy Lobectomy Lobectomy plus Pneumonectomy
1+
]
1
RESULTS OF FOLLOW-UP
It has been possible to maintain regular contact and to obtain follow-up evaluation on every patient included in this series. Uncontrolled Infection.—There have been only 2 patients in whom com bined medical and surgical measures have failed to control the atypical mycobacterial pulmonary disease. These patients are described above under operative spread of disease. One patient died of his disease 4 years after pneumonectomy, and the other continues to have positive sputum. Reactivation.—After having achieved quiescence or inactivity postoperatively, there have been 4 patients in whom disease reactivation has occurred. One occurred at 6% years following segmentectomy, and in one patient the disease reactivated 2y2 years following bilateral resections. Antimicrobial therapy had been discontinued in both patients, and re-institution of drug therapy resulted in prompt sputum conversion and clearing of the roentgeno graphic changes. Reactivation occurred in one patient 8 months following right upper and middle bi-lobectomy. This patient was sputum negative following surgery and had been allowed to leave the hospital on antituberculous drugs.
Vol. 46. No. 5 November, 1963
ATYPICAL MYCOBACTERIAL I N F E C T I O N S
697
He returned at 8 months after a prolonged alcoholic bout during which time he had stopped medications. Readmission to the hospital and continuation of the neglected chemotherapy resulted in prompt clearing of the roentgeno graphic changes and conversion of the sputum. The last reactivation occurred in a patient 7 months after right upper lobectomy. This patient had been sputum negative preoperatively, the organisms were drug susceptible, the surgical specimen was negative, and the sputum continued negative postoperatively. While the patient was still on chemotherapy, roentgenographic changes suggested disease activity in the right lower lobe, but these changes then cleared rapidly. Deaths.—Four late deaths unrelated to surgery or to activity of the atypi cal mycobacterial disease have occurred. Each of the 4 patients had been sputum negative since surgery, and each had returned to full activity. Autopsies dem onstrated no evidence of residual acid-fast disease. DISCUSSION
The surgical experience with atypical mycobacterial infections presented in this report may be favorably compared with that reported in the manage ment of tuberculosis caused by mammalian tubercle bacilli. In over 4,000 re sections for pulmonary tuberculosis collected from the recent literature (Table VI), the operative mortality averaged 6.5 per cent and the incidence of bronchopleural fistula and empyema averaged 9 per cent. Good results in control of the disease were attained in about 85 per cent of the patients.
TABLE V I .
COLLECTED RESECTIONS FOR PULMONARY
RESECTIONS PATIENTS
COMPLI CATIONS
TUBERCULOSIS*
BPF & EMPY EMA
OPERA TIVE MORTAL ITY
GOOD RESULTS
Foster et al.,5 1961 268 252 8.6% 83% 20.5% 4.1% Eldred & Sampson,e 1960 288 274 24% 7.3% 10% Floyd et al.,? 1959 430 430 18.8% 10.5% 2.3% Gebauer & Mason,s 1959 362 354 17% 4% 89% 3% Barrett et al.,» 1958 1,567 1,528 9.4% 6.2% 82.5% 2.9% Mowlem et al.,i» 1958 403 338 22% 7.7% 89% 8.2% Moore et a l . , " 1958 1,130 1.080 34% 15.5% 10% 75% Totals 4,448 4,256 6.5% 19.7% 9% ♦In over 4,000 resections for typical tuberculosis collected from the recent literature, the results expected today may be compared with the results obtained in this series of atypical mycobacterial infections.
The recorded surgical experience with atypical mycobacterial infections has originated from only five centers. The first report of surgical intervention in this disease was from the Baylor Affiliated Hospitals by Chofnas and New ton12 in 1955. These same four patients were also mentioned by Florence 13 in 1955. Jenkins and his associates2 have given further progress reports from this center. Only Group I, Mycobacterium kansasii infections were included in these
698
LAW ET
AL.
J. Thoracic and Cardiovas. Surg.
earlier reports. The present report summarizes the total surgical experience with atypical acid-fast organisms in this center. Surgical experience with predominantly Group III, or non-chromogenic infections, has been reported from three areas in the southeastern United States. Crow and co-workers14 reported the early experience at the Battey State Hospital, Rome, Georgia, in 1957, and this was incorporated in the later report by Corpe and Liang 1 in 1960. Twenty-six resections were performed in 25 patients. There were five complications (19 per cent), three of which were followed by death. A good result was obtained in 88 per cent of the patients. Of 155 patients treated with medical measures only in that hospital, there had been 31 deaths, a medical mortality rate of 20 per cent. On the basis of this experience, these authors advocated early resections in suitable candidates, and endorsed resections of less than a lobe when indicated. Taylor, 15 in 1961, reported the surgical experience of the North Carolina Sanitorium with atypical acid-fast organisms, again predominantly Group III. These patients had been included in the larger report by Floyd and his col leagues.7 There were six complications (28.5 per cent) in 21 operative pro cedures. This author concluded that the early results of surgery and the com plication rate in these patients compared favorably with the results in similar patients with infections due to M. tuberculosis treated in the same institution at the same time. In 1961, Seiler16 compiled the surgical experience with atypical mycobaeterial infections, 80 per cent of which were Group III, from several Florida hospitals. There had been 92 resections performed in 82 patients, with ten complications (10.9 per cent), two of which resulted in death. After an aver age follow-up of 18.9 months, 87.8 per cent of the patients were classified as having good results. On the basis of this combined experience, Seiler suggested that a high degree of success can be expected from surgical intervention in this disease, although some increase in morbidity and mortality can be antici pated. Segmental resection was not recommended. The only reports of unfavorable experience in the surgical management of atypical acid-fast disease have originated in the Midwest. Initially reported by Lester and associates,17 in 1958, and later by Harrison and co-authors 18 in 1959, this experience included 30 operative procedures in 24 patients with Mycobacterium kansasii (Group I, or photochromogenic) infections, with a major complication rate of 30 per cent. Only 14 of these operative procedures were pulmonary resections, and the major complication rate in this group was 35.7 per cent. Also reported were 10 patients with Group II, or skotochromogenic, infections successfully treated surgically without major complications. On the basis of this experience, these authors advocated greater attention to achieving negative sputum status prior to undertaking surgical therapy, and have strongly recommended lobectomy as the minimal extent of resection to be employed. Although the total surgical experience with atypical mycobacterial pul monary disease is limited, the results reported thus far (Table VII) compare
ATYPICAL MYCOBACTERIAL INFECTIONS
Vol. 46, No. 5
November, 1963
699
favorably with the results expected today in the surgical treatment of typical tuberculosis (Table V I ) . The experience with Group I infections presented here and the experience reported with Group I I I infections 1 ' 15 ' 16 suggest pos sible differences in the response of these infections, but no definite statement can be made from the available material. The need for further accumulation of accurately reported surgical experience in atypical mycobacterial disease is obvious. The current pessimistic or overly cautious attitude toward this disease should be discarded. TABLE V I I .
AUTHOR
R E S U L T S OF SURGERY IN ATYPICAL MYCOBACTERIAL D I S E A S E *
PATIENTS
BACTER IOLOGY
COMPLICA TIONS
MORTALITY
Harrison et al. 1 8 1959
24 10
I II
30% 0
0 0
Corpe & Liangi 1960
2 1 22
I II III
19%
12%
Taylor™ 1961
5 3 12
I 1 II III
28.5%
Sellers 1961
82
I I I ( 80%)
10.8%
UNCON TROLLED
GOOD RESULTS
2 pts. 0
91.5% 100%
0
88%
5%
2 pts.
85%
2.4%
8 pts.
87.8%
I 1 56 2 II Law et al. 2 pts. 11.7% 0 97% 5 1963 III 1 IV •Comparison of the total reported experience in the surgical management of atypical myco bacterial disease reveals that there has been an acceptable morbidity and mortality, and that the ultimate good results are excellent. This is true for both Group III and Group I infections.
The availability of potent antimicrobial drugs must be given pre-eminent credit for the development of resective surgery for pulmonary tuberculosis during the past decade. However, the contributions made by improved surgical techniques, advances in anesthesia, the availability of whole blood transfusions, and increased knowledge of cardiopulmonary physiology are too frequently forgotten. There is little evidence to support the comparison of the risk of sur gery in atypical Mycobacteria with the risk in drug resistant M. tuberculosis, or the risk in either of these with risk of surgery in the pre-chemotherapy era. The experience with surgical intervention in pulmonary disease caused by atypical Mycobacteria, principally Mycobacterium kansasii, that has been gained during the past 10 years in the Baylor Affiliated Hospitals is the basis for cer tain recommendations. An adequate and carefully planned medical program, including multiple drug chemotherapy, should be initiated. 2 The continued excretion of positive sputum and the emergence of drug resistant organisms are indications, rather than contraindications, for surgical intervention; how ever, roentgenographic evaluation of the disease should show clearing or sta bility. Whenever possible, a decision about the need for surgical intervention should be made early (i.e., third to sixth month), and the operation accom plished promptly.
700
LAW ET AL.
J. Thoracic and Cardiovas. Surg.
The extent of pulmonary tissue to be resected is decided on the basis of the disease found at thoracotomy and the patient's general condition. Segmentectomy has given results equal to or better than the results of lobectomy in our hands. Carefully planned and skillfully performed surgery coupled with meticulous postoperative care will result in minimal complications. I t is the current policy to continue conventional chemotherapy for one year, or more, postoperatively. SUMMARY
During the past 10 years, 68 elective surgical procedures have been per formed in 64 patients for granulomatous pulmonary disease caused by atypical Mycobacteria. There has been no operative mortality. Complications of surgery have occurred in 28 per cent, of which 11.7 per cent have been major compli cations. One patient continues to have positive sputum, and one patient died of his disease 4 years after surgery. After achieving negative sputum status postoperatively, reactivation of disease occurred in 4 patients, but has subse quently been controlled by chemotherapy. There have been 4 late deaths unre lated to the atypical mycobacterial disease. Sputum postivity and drug resistance of the organisms have not influenced the morbidity or ultimate control of the disease. The judicious and effective utilization of standard surgical measures, in combination with a vigorous chemotherapeutic program, has achieved a good result in 97 per cent of this group of patients. Pulmonary resections of limited extent have been found safe and effective. Skillfully performed surgery and meticulous postoperative care have been found to be the major factors in achieving good results. REFEBKNCES 1. Corpe, K. F . , and Liang, J . : Surgical Resection in Pulmonary Tuberculosis Due to Atypi cal Mycobacterium Tuberculosis, J . THORACIC & CARDIOVAS. SURG. 40: 93, 1960.
2a. Jenkins, D. E., Bahar, D., Chofnas, I., Foster, R., and Barkley, H . T.: The Clinical Problem of Infection With Atypical Acid-Fast Bacilli, Tr. Am. Clin. & Climatol. A. 7 1 : 21, 1959. 2b. Bahar, D., Chofnas, I., and Jenkins, D. E . : Long-Term Results of Medical a n d Surgical Treatment of Pulmonary Disease Due to Mycobacteriwm Tcansasii, Am. Rev. Resp. Dis. 84: 127, 1961. (Abst.) 3. Diagnostic Standards and Classification of Tuberculosis. National Tuberculosis Associa tion, New York, 1961, p . 39. 4. Runyon, E. H., Runyon, L. C , Brisbay, J . E_^ Dietz, T. M., Raniga, P . L., and Smith, M. J . : Classification of Mycobacterial Pathogens: An Evaluation of Some New Diagnostic Procedures in Transactions of the Twenty-first Research Conference in Pulmonary Diseases, Veterans Administration—Armed Forces, Washington, D. C , 1962, Government Printing Office, p . 153. 5. Foster, J . H., Killen, D. A., Diveley, W. L., MeCracken, R. L., and Hubbard, W. W.: Pulmonary Resection in the Treatment of Tuberculosis, Dis. Chest 40: 5, 1961. 6. Eldred, W. J., and Sampson, P . C : An Inquiry Into t h e Causes and Prevention of Com plications in Resection Surgery for Pulmonary Tuberculosis, J . THORACIC & CAR DIOVAS. SURG. 3 9 : 716,1960.
7. Floyd, R. D, Hollister, W F . , and Sealy, W. C : Complications in 430 Consecutive Pul monary Resections for Tuberculosis, Surg. Gynec. & Obst. 109: 467, 1959. 8. Gebauer, P . W., and Mason, C. B . : Analysis and Late Results of Resection for Pulmonary Tuberculosis in Hawaii, Am. Rev. Resp. Dis. 80: 6, 1959.
Vol. 46, No. 5
A T Y P I C A L MYCOBACTERIAL I N F E C T I O N S
November, 1963
701 '
V ±
9. Barrett, B . X , Neal, H . S., Day, J . C , Chapman, P . T., O'Eourke, P . V., O'Brien, E . J., and T u t t l e W. M.: Pulmonary Besection in t h e Treatment of Tuberculosis, J . THORACIC SURG. 36: 803, 1958.
10. Movvlem, A., Connolly, C. J., and Zimmerman, B . : The Surgical Treatment of Pulmonary Tuberculosis in the Mentally 111, Surgery 4 3 : 913, 1958. 11. Moore, J . A., Walkup, H . E., Bayl, J . E., and Chapman, J . P., J r . : E n d Eesults of Pul monary Besection for Tuberculosis, Ann. Surg. 147: 659, 1958. 12. Chofnas, I., and Newton, J . : Pneumonitis Due to Chromogenic Acid-Fast Bacilli in Trans actions of Fourteenth Conference on the Chemotherapy of Tuberculosis, Veterans Ad ministration-Army-Navy, Washington, D. C , 1955, Government Printing Office, p . 205. 13. Florence, H . : Atypical Acid-Fast (Chromogenic) Organisms Complicating Pulmonary Dis ease, Dis. Chest. 30: 250, 1956. 14. Crow, H . E., King, C. T., Smith, C. E., Corpe, B . F . , and Stergus, I . : A Limited Clin ical, Pathologic, and Epidemiologic Study of Patients With Pulmonary Lesions Associated With Atypical Acid-Fast Bacilli in the Sputum, Am. Bev. Tuberc. 7 5 : 199, 1957. 15. Taylor, A. J . : The Surgical Treatment of Patients With Infections of the Lung Due to Unclassified Acid-Fast Bacilli, Am. Bev. Besp. Dis. 83: 127, 1961. 16. Seiler, H . I I . : Pulmonary Besection in the Treatment of Atypical Myeobacterial Infec tions. Presented to Southern Thoracic Society, Hot Springs, Arkansas, Sept. 6-8, 1961. 17. Lester, W., J r . , Botkin, J., and Colton, B . : An Analysis of Forty-nine Cases of Pulmonary Disease Caused by Photochromogenic Mycobacteria in Transactions of Seventeenth Conference on Chemotherapy of Tuberculosis. Veterans Administration-Armed Forces, Washington, D. C , 1958, Government Printing Office, p . 289. 18. Harrison, B. W., Beimann, A. F . , Long, E. T., Lester, W., J r . , and Adams, W. E . : Adverse Surgical Experience in the Treatment of Pulmonary Disease Caused by Atypical Acid-Fast Bacilli, J . THORACIC & CARDIOVAS. SURG. 3 8 : 481, 1959.
(For Discussion, see page 713)
INFECTIONS
Daniel E. Jenkins,
Irving Chofnas, M.D.***
David Bahar, M.D.**** (by invitation),
(by invitation),
MANAGEMENT
(by invitation),
(by
invitation),
Frances Whit comb,
H. T. Barkley, M.D.,******
Michael E. De Bakey, M.D.,*******
M.D.**
Houston,
M.S.*****
and Texas
T
HE atypical or unclassified Mycobacteria are now widely recognized and accepted as the causative agents of granulomatous pulmonary disease in humans. The pulmonary disease caused by these atypical acid-fast organisms is similar, both clinically and roentgenographically, to disease caused by Mycobacterium tuberculosis. Identification of the atypical mycobacterial infection is primarily dependent upon the astuteness of the bacteriologist, and may not occur until after the patient has been hospitalized and treated from 4 to 6 weeks as having a typical tuberculous infection. The subsequent management and evaluation of response to therapy is, therefore, frequently governed by guide lines established for the treatment of disease caused by M. tuberculosis. However, increasing experience with disease caused by the atypical Mycobacteria suggests that there are sufficient differentiating clinical features to justify estab lishing specific treatment programs and evaluation criteria. The frequent observation of in vitro resistance to the antituberculous chemotherapeutic drugs by the atypical Mycobacteria, either on pre-treatment studies or emerging early in the course of treatment, has been a source of significant concern. Similarly, the response of these patients to drug therapy may be slow or absent. In 180 patients with atypical mycobacterial pulmonary disease, principally Group I I I infections, Corpe and Liang 1 observed a sputum Prom the Cora and Webb Mading Department of Surgery, the Departments of Medicine and Microbiology, Baylor University College of Medicine, the Veterans Administration Hospital, and the Pulmonary Disease Section of Jefferson Davis Hospital, Houston, Texas. Supported in part by the U. S. Public Health Service (E-3373). Read a t the Forty-third Annual Meeting of The American Association for Thoracic Sur gery a t Houston, Texas, April 8-10, 1963. •Chief, Surgical Service, Veterans Administration Hospital. ♦•Professor of Medicine, Baylor University College of Medicine. •••Chief, Pulmonary Disease Section, Veterans Administration Hospital. ••••Assistant Director, Tuberculosis Division, Jefferson Davis Hospital. •••••Research Bacteriologist, Pulmonary Disease Laboratory, Veterans Administration Hospital. ••••••Chief of Surgery, Tuberculosis Division, Jefferson Davis Hospital. •••••••Professor and Chairman, Cora and Webb Mading Department of Surgery, Baylor University College of Medicine. 689
690
LAW E T AL.
J. Thoracic and Cardiovas. Surg.
conversion rate of 22 per cent after 6 months of conventional antitubereulous chemotherapy. In the same hospital there was a sputum conversion rate of 90 per cent after 6 months of similar therapy in patients with disease caused by M. tuberculosis. Bahar, Chofnas, and Jenkins 2 have reported a sputum con version rate of 60 per cent after 6 months of drug therapy in 73 patients with disease due to Mycobacterium kansasii, or Group I organisms. This delayed response to medical treatment and the frequent presence of drug resistance have caused serious concern about the safety of surgical inter vention in atypical mycobacterial disease. However, these same factors signifi cantly increase the potential usefulness of resective surgery in the control of this disease. This report will evaluate the safety and effectiveness of surgery in the management of pulmonary disease caused by atypical Mycobacteria from the extensive experience in this center, principally with Group I organisms, and from the experience recorded by others. 24 22 20 18 16
H I Jeff. Davis
rjV.A.H. ^^
-12 «10 « 8 a- 6 4 2 20-29 30-39 40-49 50-59 60-69 Age in Years Pig. 1.—Age of patients. MATERIAL
In the Baylor Affiliated Hospitals, from June 3, 1952, through June 30, 1962, there have been 68 elective thoracic surgical procedures performed on 64 patients with infections caused by atypical Mycobacteria. Each patient has had clinical and roentgenographic evidence of granulomatous pulmonary disease, and each operation was designed to convert positive sputum or to remove a major disease residual. No patient is included who has had an incidental single isolation of atypical Mycobacteria, and no patient exhibiting a mixed infection, with isolation of both atypical Mycobacteria and M. tuberculosis, is included. The 64 patients have ranged in age from 29 to 68 years (Fig. 1); 57 were Caucasian and 7 were Negro; 61 were male and 3 were female. Forty-four of the operations were performed on 43 patients at the Veterans Administration Hospital, and 24 operations were performed on 21 patients through the Tuber culosis Division of the Jefferson Davis Hospital, a city-county institution. This may partially explain the age and sex distribution, but the high incidence of this disease in the older white male has been previously noted.2"'1G
Vol. 46. No. 5 November, 1963
ATYPICAL MYCOBACTEKIAL I N F E C T I O N S
691
On admission to the hospital, the pulmonary disease present in these pa tients was classified3 as minimal in 3 patients, moderately advanced in 35 patients, 6 of which were bilateral, and far advanced in 26 patients, 19 of which were bilateral (Table I ) . TABLE I. |
E X T E N T OP D I S E A S E ON ADMISSION
UNILATERAL
|
Minimal 3 Moderately advanced 29* F a r advanced 7t Totals 39 •Three complications occurred (or encountered). tTwo complications occurred.
BILATERAL
6 19* 25
|
TOTALS
3 35 26 64
Bacteriology.—The criteria and classification of Runyon 4 have been used in the identification of the atypical Mycobacteria in this laboratory throughout the period of this report. The interchange of cultures with Dr. Runyon 's labora tory has been sufficient to establish unequivocally the uniformity of identifica tion and classification. In 56 of the patients included in this report, the causative organisms were Runyon's Group I or photochromogens, now designated Mycobacterium kansasii; in 2 patients the causative organisms were Runyon's Group II, or skotochromogens; in 5 patients the organisms were Runyon's Group III, or non-chromogens; and in one patient the organisms were Runyon's Group IV, or rapid growers. Al though this report includes every patient with atypical mycobacterial pulmonary disease who underwent surgery in this center, the major interest is in the extensive experience with pulmonary disease caused by Mycobacterium kansasii, or Group I organisms. The same species of acid-fast organisms was found throughout the course of the disease in each patient, and the organisms found in the positive surgical specimens were always the same as had previously been isolated from the sputum. A positive sputum culture had been obtained during the 90 days pre ceding the surgical procedure in 47 of the 68 patients (69 per cent). Atypical acid-fast organisms were found on smear or culture or both in 47 of the 60 surgical specimens (78 per cent). Thus, viable atypical acid-fast organisms were recovered from the sputum preoperatively or from the surgical specimen in 58 of the 68 operations (85 per cent). In vitro antituberculous drug susceptibility studies were performed re peatedly on the organisms obtained from each patient. These studies have been performed and interpreted according to the Laboratory Methods of the Veterans Administration-Armed Forces Cooperative Study on the Chemotherapy of Tuberculosis. A previous report 2 " has discussed the problems of natural re sistance and rapidly emerging resistance of these atypical organisms to the individual antituberculous drugs. In the retrospective study of this group of patients, the last available preoperative susceptibility tests have been used to
LAW ET AL.
692
J. Thoracic and Cardiovas. Surg.
place each patient in one of three arbitrary groups, based on the estimated effectiveness of the chemotherapeutie program: "effective chemotherapy," pa tients whose organisms were susceptible to two or more of the drugs being administered; "partially effective chemotherapy," patients whose organisms demonstrated resistance to some drags, but the patient was receiving one drug to which the organisms were susceptible; and "ineffective chemotherapy," pa tients whose organisms were resistant to all of the antituberculous drugs which the patient was receiving, or the patient received no drugs preoperatively. (See Table V.)
Fig. 2.—Duration of preoperative chemotherapy. MEDICAL TREATMENT
The medical treatment of these patients has consisted of hospitalization, a limited but confining rest program, and antimicrobial drugs. 2 The majority of the patients have received isoniazid, 5 to 10 mg. of body weight per day, in combination with sodium para-aminosalicylate, 15 Gm. daily, or streptomycin, 1 Gm. twice weekly. Some patients have received, in addition, courses of kanamyein, cycloserine, pyrazinamide, a sulfonamide, or tetracycline. There has not been a uniform policy of additional drug coverage in the preoperative period. The duration of preoperative chemotherapy in these patients has varied from none in 5 patients to over 5 years in 2 patients (Fig. 2). The small number of patients and the wide variability in type and extent of disease encountered in this group of patients prevents identification of an optimum duration of preoperative chemotherapy and emphasizes the necessity of individualizing each patient's treatment program. Preoperative bronchoscopy has been performed routinely. With the excep tion of the 2 patients with total destruction of a lung requiring pneumonectomy, endobronchial disease has not been encountered. Since it has not been customary
Vol. 46 No S
ATYPICAL MYCOBACTERIAL I N F E C T I O N S
November, 1963
fiq3
U J O
to bronchoscope these patients prior to initiation of chemotherapy, the possible role of endobronchitis in untreated disease due to the atypical Myeobacteria cannot be evaluated. SURGICAL TREATMENT
Every patient considered for surgery has been evaluated by a MedicalSurgical Conference. Each patient for whom surgery was recommended had demonstrated some response to treatment with roentgenographic evidence of either clearing or stability of the pulmonary lesion. The primary indications for surgery have been failure to convert sputum, the persistence of a cavity beyond the third month of treatment, unresolved large nodular or caseous re sidual, and destroyed lung. Other factors considered in the decision to recom mend surgery have been the demonstration of resistance in drug susceptibility studies, the younger age group, and the presence of a socioeconomic background which would make prolonged cooperation in treatment doubtful. Excisional surgery has been recommended in every patient with sufficient pulmonary reserve to tolerate resection. The extent of each resection performed has been based on the surgeon's evaluation of the disease found at thoracotomy, without consideration of the patient's sputum status or drug susceptibility studies. The guiding principle has been the maximum preservation of function ing pulmonary tissue consistent with adequate removal of the disease. Segmental resection has been used when the major disease focus could be removed through a clean intersegmental plane. The term "lobectomy plus" includes bi-lobectomy as well as lobectomy plus segmentectomy. The proportionate number of each type of operative procedure performed in each year of this study has remained relatively uniform (Table I I ) . The collapse procedures include one thoracoplasty and seven extraperiosteal Ivalon plombages. In 2 patients the plombage was a planned pre-resection col lapse. In the remaining 6 patients, collapse was selected as the only feasible surgical procedure for a patient in whom the disease could not be controlled with medical therapy alone, but with a pulmonary reserve too limited to permit excisional surgery. Multiple pi-ocedures were performed in 3 patients. In each instance the sequence of surgical attack was planned at the initial therapy conference as TABLE I I .
11952 Collapse Wedge Segmentectomy Lobectomy Lobectomy plus Pneumonectomy Totals
1953 1954
1955
SURGICAL
1956
1
1
1
2 1
1
It 4
1 It 1 3
2 2
PROCEDURES*
1957 1958 2 2 1 3 2 6 1 It 8
10
1959 1 1 4 6 It 13
1960 1961 | 1962 1 1 2t 4 5t 1 11
2 5t 1 10
4t
5
TOTALS
8 3 21 28 6 2 68
•The proportionate number of each type of operative procedure performed during each year of this study has remained relatively uniform. The term "lobectomy plus" includes biIobectomy and lobectomy plus segmentectomy. tOne complication occurred.
J. Thoracic and Cardiovas. Surg.
LAW E T AL.
694
the ideal management of extensive disease. One patient had a left extraperiosteal plombage followed by left upper lobectomy, another patient had a left apical-posterior segmentectomy followed by right upper lobectomy, and one patient had a left extraperiosteal plombage, a right apical-posterior segmenjtectomy, and then a left upper lobectomy. The operative procedures and the postoperative care of the patients have been performed by residents under the supervision of the teaching staff. COMPLICATIONS OF SURGERY
There has been no operative mortality in this group of patients. Nineteen complications have occurred in the performance of 68 operative procedures, a total complication rate of 28 per cent (Table I I I ) . TABLE I I I .
Resections—60 Bronchopleural Delayed expansion Operative spread Wound infection Serum hepatitis Subclavian artery injury Intestinal obstruction Cardiac arrhythmia Total Collapse—8 Infection of plombage Postoperative psychosis Total
COMPLICATIONS OF SURGERY
fistula
4 4 3 2 1 1 1 1 17 1 1 2
6.6 6.6 5.0 3.3 1.6 1.6 1.6 1.6 28.8% 12.5 12.5 25%
In comparing this series of patients with other reports, it is evident that some authors have restricted their attention to those complications considered to be directly related to the activity of the acid-fast disease, the drug resistance of the organisms, or compromising successful control of the disease. For this reason, this artificial distinction will be made here, and primary attention will be directed to eight of the complications. These include 4 bronchopleural fistulas, 3 instances of disease spread, and a pyogenic infection of an extraperiosteal Ivalon plombage (11.7 per cent). Four bronchopleural fistulas have occurred following the 60 resective pro cedures, an incidence of 6.6 per cent. Two fistulas followed lobectomy, and one developed after a right upper lobectomy and superior segmentectomy. Tailoring thoracoplasties have controlled the fistulas, and the patients remain sputum negative. The fourth fistula developed after right apical-posterior segmentectomy. Because of rapid subsidence of systemic signs and of poor gen eral condition in a psychotic patient who will require prolonged hospitalization, a course of observation was elected. The patient continues to improve, the pleural pocket is decreasing in size, and the sputum is negative. A thoracoplasty will probably be required eventually.
Vol. 46, No. 5 November, 1963
A T Y P I C A L MYCOBACTERIAL I N F E C T I O N S
695 vo °
Disease spread or reactivation occurred postoperatively in 3 patients. In one patient, during the first month after bi-lobectomy, roentgenographic changes appeared but cleared rapidly on continued drug therapy. The patient has not had positive sputum since operation. Disease spread occurred on the contralateral side following bi-lobectomy in a patient with Group I I I or non-chromogenic organisms, who has continued to have positive sputum. A cavity in the left lung of a third patient reopened after right pneumonectomy and he con tinued sputum positive until his death 4 years later. The last 2 patients will be mentioned again as the only 2 patients in this group whose disease has not been controlled by the medical-surgical program. The infection of the Ivalon plombage (the procedure had been performed in this patient because of persistence of cavity despite sputum negativity for 13 months) required conversion to a thoracoplasty on the sixteenth postopera tive day. The staphylococcal infection was controlled with difficulty, but the subscapular space closed, and the patient remained sputum negative. In relating the operative procedures and complications to the species of atypical organism, it is noted that 60 operative procedures were performed in 56 patients with Mycobact&rium kansasii, Group I, or photochromogenic or ganisms (Table I V ) . All of the complications have occurred in this group ex cept those mentioned below. There have been two surgical procedures per formed in patients with Group II, or skotochromogenic organisms, a lobectomy and a pneumonectomy, each performed without complication. In the 5 patients with Group III, non-chromogens or Battey strains, there has been one plombage without complication, one segmentectomy followed by delayed expansion, one lobectomy which was followed by a wound infection, and two "lobectomy plus" procedures, one of which was followed by a disease spread. Thus, in the 5 pa tients with Group I I I infections, there were three complications, only one of which was related to the acid-fast disease (20 per cent). The patient with Group IV organisms underwent lobectomy uneventfully. The principal complications encountered in this series of patients are pre sented in Table V in relation to the patient's sputum status at surgery, and the estimated effectiveness of the chemotherapy administered preoperatively. The high incidence of complications in the "lobectomy plus" and "pneumonec-
TABLE
IV.
BACTERIOLOGIC CLASSIFICATION |
GROUP I
|
GROUP II
|
AND
SURGICAL
GROUP
in
|
COMPLICATIONS* GROUP IV
|
TOTALS
1 8 Collapse 7t 3 Wedge 3 1 21 Segmentecotmy 201 1 1 1 28 Lobectomy 25} 6 Lobectomy plus 2t 4* 1 2 Pneumonectomy It 1 60 2 5 68 Totals •All of the principal complications encountered occurred in the patients with Group I infections, except for one instance of disease spread which occurred in a patient with Group III infection following bi-lobectomy. tOne complication occurred. {Two complications occurred.
696
LAW ET AL.
J. Thoracic and Cardiovas. Surg.
tomy" groups is probably related to efforts to control extensive disease. In comparing the "segmentectomy" and "lobectomy" groups, it may be seen that the complications encountered were not directly related to sputum positivity or drug resistance of the organisms. The records of this group of patients have been repeatedly analyzed in relation to the possible protective role of preoperative sputum negativity or bacterial drug susceptibility, in relation to the preoperative roentgenographic response of the patient's disease, and in relation to the adequacy and length of preoperative drug therapy. It has not been possible to correlate any of these factors with the occurrence of surgical complications, or the patient's response to surgery. It has become increasingly evident that carefully planned and skillfully performed surgery with meticulous postopera tive care are of the utmost importance in the successful conduct of these pa tients through an operation. TABLE V.
CHEMOTHERAPY EFFECTIVENESS AND SURGICAL COMPLICATIONS* S P U T U M POSITIVE
S P U T U M NEGATIVE EFFECTIVE
PARTIALLY EFFECTIVE
INEFFEC TIVE
EFFECTIVE
PARTIALLY EFFECTIVE
INEFFEC TIVE
TOTALS
8 5 3 1 2 21 2 9t 4 1 3 2 28 13 1 5 4 2t 3t 6 2* 4t 2 1 It 34 68 3 10 7 11 Totals 3 ♦The principal complications encountered have not been easily correlated with the patient's sputum status at the time of surgery, or with an arbitrary estimate of the effectiveness of the chemotherapeutic program. tOne complication occurred. JTwo complications occurred. Collapse Wedge Segmentectomy Lobectomy Lobectomy plus Pneumonectomy
1+
]
1
RESULTS OF FOLLOW-UP
It has been possible to maintain regular contact and to obtain follow-up evaluation on every patient included in this series. Uncontrolled Infection.—There have been only 2 patients in whom com bined medical and surgical measures have failed to control the atypical mycobacterial pulmonary disease. These patients are described above under operative spread of disease. One patient died of his disease 4 years after pneumonectomy, and the other continues to have positive sputum. Reactivation.—After having achieved quiescence or inactivity postoperatively, there have been 4 patients in whom disease reactivation has occurred. One occurred at 6% years following segmentectomy, and in one patient the disease reactivated 2y2 years following bilateral resections. Antimicrobial therapy had been discontinued in both patients, and re-institution of drug therapy resulted in prompt sputum conversion and clearing of the roentgeno graphic changes. Reactivation occurred in one patient 8 months following right upper and middle bi-lobectomy. This patient was sputum negative following surgery and had been allowed to leave the hospital on antituberculous drugs.
Vol. 46. No. 5 November, 1963
ATYPICAL MYCOBACTERIAL I N F E C T I O N S
697
He returned at 8 months after a prolonged alcoholic bout during which time he had stopped medications. Readmission to the hospital and continuation of the neglected chemotherapy resulted in prompt clearing of the roentgeno graphic changes and conversion of the sputum. The last reactivation occurred in a patient 7 months after right upper lobectomy. This patient had been sputum negative preoperatively, the organisms were drug susceptible, the surgical specimen was negative, and the sputum continued negative postoperatively. While the patient was still on chemotherapy, roentgenographic changes suggested disease activity in the right lower lobe, but these changes then cleared rapidly. Deaths.—Four late deaths unrelated to surgery or to activity of the atypi cal mycobacterial disease have occurred. Each of the 4 patients had been sputum negative since surgery, and each had returned to full activity. Autopsies dem onstrated no evidence of residual acid-fast disease. DISCUSSION
The surgical experience with atypical mycobacterial infections presented in this report may be favorably compared with that reported in the manage ment of tuberculosis caused by mammalian tubercle bacilli. In over 4,000 re sections for pulmonary tuberculosis collected from the recent literature (Table VI), the operative mortality averaged 6.5 per cent and the incidence of bronchopleural fistula and empyema averaged 9 per cent. Good results in control of the disease were attained in about 85 per cent of the patients.
TABLE V I .
COLLECTED RESECTIONS FOR PULMONARY
RESECTIONS PATIENTS
COMPLI CATIONS
TUBERCULOSIS*
BPF & EMPY EMA
OPERA TIVE MORTAL ITY
GOOD RESULTS
Foster et al.,5 1961 268 252 8.6% 83% 20.5% 4.1% Eldred & Sampson,e 1960 288 274 24% 7.3% 10% Floyd et al.,? 1959 430 430 18.8% 10.5% 2.3% Gebauer & Mason,s 1959 362 354 17% 4% 89% 3% Barrett et al.,» 1958 1,567 1,528 9.4% 6.2% 82.5% 2.9% Mowlem et al.,i» 1958 403 338 22% 7.7% 89% 8.2% Moore et a l . , " 1958 1,130 1.080 34% 15.5% 10% 75% Totals 4,448 4,256 6.5% 19.7% 9% ♦In over 4,000 resections for typical tuberculosis collected from the recent literature, the results expected today may be compared with the results obtained in this series of atypical mycobacterial infections.
The recorded surgical experience with atypical mycobacterial infections has originated from only five centers. The first report of surgical intervention in this disease was from the Baylor Affiliated Hospitals by Chofnas and New ton12 in 1955. These same four patients were also mentioned by Florence 13 in 1955. Jenkins and his associates2 have given further progress reports from this center. Only Group I, Mycobacterium kansasii infections were included in these
698
LAW ET
AL.
J. Thoracic and Cardiovas. Surg.
earlier reports. The present report summarizes the total surgical experience with atypical acid-fast organisms in this center. Surgical experience with predominantly Group III, or non-chromogenic infections, has been reported from three areas in the southeastern United States. Crow and co-workers14 reported the early experience at the Battey State Hospital, Rome, Georgia, in 1957, and this was incorporated in the later report by Corpe and Liang 1 in 1960. Twenty-six resections were performed in 25 patients. There were five complications (19 per cent), three of which were followed by death. A good result was obtained in 88 per cent of the patients. Of 155 patients treated with medical measures only in that hospital, there had been 31 deaths, a medical mortality rate of 20 per cent. On the basis of this experience, these authors advocated early resections in suitable candidates, and endorsed resections of less than a lobe when indicated. Taylor, 15 in 1961, reported the surgical experience of the North Carolina Sanitorium with atypical acid-fast organisms, again predominantly Group III. These patients had been included in the larger report by Floyd and his col leagues.7 There were six complications (28.5 per cent) in 21 operative pro cedures. This author concluded that the early results of surgery and the com plication rate in these patients compared favorably with the results in similar patients with infections due to M. tuberculosis treated in the same institution at the same time. In 1961, Seiler16 compiled the surgical experience with atypical mycobaeterial infections, 80 per cent of which were Group III, from several Florida hospitals. There had been 92 resections performed in 82 patients, with ten complications (10.9 per cent), two of which resulted in death. After an aver age follow-up of 18.9 months, 87.8 per cent of the patients were classified as having good results. On the basis of this combined experience, Seiler suggested that a high degree of success can be expected from surgical intervention in this disease, although some increase in morbidity and mortality can be antici pated. Segmental resection was not recommended. The only reports of unfavorable experience in the surgical management of atypical acid-fast disease have originated in the Midwest. Initially reported by Lester and associates,17 in 1958, and later by Harrison and co-authors 18 in 1959, this experience included 30 operative procedures in 24 patients with Mycobacterium kansasii (Group I, or photochromogenic) infections, with a major complication rate of 30 per cent. Only 14 of these operative procedures were pulmonary resections, and the major complication rate in this group was 35.7 per cent. Also reported were 10 patients with Group II, or skotochromogenic, infections successfully treated surgically without major complications. On the basis of this experience, these authors advocated greater attention to achieving negative sputum status prior to undertaking surgical therapy, and have strongly recommended lobectomy as the minimal extent of resection to be employed. Although the total surgical experience with atypical mycobacterial pul monary disease is limited, the results reported thus far (Table VII) compare
ATYPICAL MYCOBACTERIAL INFECTIONS
Vol. 46, No. 5
November, 1963
699
favorably with the results expected today in the surgical treatment of typical tuberculosis (Table V I ) . The experience with Group I infections presented here and the experience reported with Group I I I infections 1 ' 15 ' 16 suggest pos sible differences in the response of these infections, but no definite statement can be made from the available material. The need for further accumulation of accurately reported surgical experience in atypical mycobacterial disease is obvious. The current pessimistic or overly cautious attitude toward this disease should be discarded. TABLE V I I .
AUTHOR
R E S U L T S OF SURGERY IN ATYPICAL MYCOBACTERIAL D I S E A S E *
PATIENTS
BACTER IOLOGY
COMPLICA TIONS
MORTALITY
Harrison et al. 1 8 1959
24 10
I II
30% 0
0 0
Corpe & Liangi 1960
2 1 22
I II III
19%
12%
Taylor™ 1961
5 3 12
I 1 II III
28.5%
Sellers 1961
82
I I I ( 80%)
10.8%
UNCON TROLLED
GOOD RESULTS
2 pts. 0
91.5% 100%
0
88%
5%
2 pts.
85%
2.4%
8 pts.
87.8%
I 1 56 2 II Law et al. 2 pts. 11.7% 0 97% 5 1963 III 1 IV •Comparison of the total reported experience in the surgical management of atypical myco bacterial disease reveals that there has been an acceptable morbidity and mortality, and that the ultimate good results are excellent. This is true for both Group III and Group I infections.
The availability of potent antimicrobial drugs must be given pre-eminent credit for the development of resective surgery for pulmonary tuberculosis during the past decade. However, the contributions made by improved surgical techniques, advances in anesthesia, the availability of whole blood transfusions, and increased knowledge of cardiopulmonary physiology are too frequently forgotten. There is little evidence to support the comparison of the risk of sur gery in atypical Mycobacteria with the risk in drug resistant M. tuberculosis, or the risk in either of these with risk of surgery in the pre-chemotherapy era. The experience with surgical intervention in pulmonary disease caused by atypical Mycobacteria, principally Mycobacterium kansasii, that has been gained during the past 10 years in the Baylor Affiliated Hospitals is the basis for cer tain recommendations. An adequate and carefully planned medical program, including multiple drug chemotherapy, should be initiated. 2 The continued excretion of positive sputum and the emergence of drug resistant organisms are indications, rather than contraindications, for surgical intervention; how ever, roentgenographic evaluation of the disease should show clearing or sta bility. Whenever possible, a decision about the need for surgical intervention should be made early (i.e., third to sixth month), and the operation accom plished promptly.
700
LAW ET AL.
J. Thoracic and Cardiovas. Surg.
The extent of pulmonary tissue to be resected is decided on the basis of the disease found at thoracotomy and the patient's general condition. Segmentectomy has given results equal to or better than the results of lobectomy in our hands. Carefully planned and skillfully performed surgery coupled with meticulous postoperative care will result in minimal complications. I t is the current policy to continue conventional chemotherapy for one year, or more, postoperatively. SUMMARY
During the past 10 years, 68 elective surgical procedures have been per formed in 64 patients for granulomatous pulmonary disease caused by atypical Mycobacteria. There has been no operative mortality. Complications of surgery have occurred in 28 per cent, of which 11.7 per cent have been major compli cations. One patient continues to have positive sputum, and one patient died of his disease 4 years after surgery. After achieving negative sputum status postoperatively, reactivation of disease occurred in 4 patients, but has subse quently been controlled by chemotherapy. There have been 4 late deaths unre lated to the atypical mycobacterial disease. Sputum postivity and drug resistance of the organisms have not influenced the morbidity or ultimate control of the disease. The judicious and effective utilization of standard surgical measures, in combination with a vigorous chemotherapeutic program, has achieved a good result in 97 per cent of this group of patients. Pulmonary resections of limited extent have been found safe and effective. Skillfully performed surgery and meticulous postoperative care have been found to be the major factors in achieving good results. REFEBKNCES 1. Corpe, K. F . , and Liang, J . : Surgical Resection in Pulmonary Tuberculosis Due to Atypi cal Mycobacterium Tuberculosis, J . THORACIC & CARDIOVAS. SURG. 40: 93, 1960.
2a. Jenkins, D. E., Bahar, D., Chofnas, I., Foster, R., and Barkley, H . T.: The Clinical Problem of Infection With Atypical Acid-Fast Bacilli, Tr. Am. Clin. & Climatol. A. 7 1 : 21, 1959. 2b. Bahar, D., Chofnas, I., and Jenkins, D. E . : Long-Term Results of Medical a n d Surgical Treatment of Pulmonary Disease Due to Mycobacteriwm Tcansasii, Am. Rev. Resp. Dis. 84: 127, 1961. (Abst.) 3. Diagnostic Standards and Classification of Tuberculosis. National Tuberculosis Associa tion, New York, 1961, p . 39. 4. Runyon, E. H., Runyon, L. C , Brisbay, J . E_^ Dietz, T. M., Raniga, P . L., and Smith, M. J . : Classification of Mycobacterial Pathogens: An Evaluation of Some New Diagnostic Procedures in Transactions of the Twenty-first Research Conference in Pulmonary Diseases, Veterans Administration—Armed Forces, Washington, D. C , 1962, Government Printing Office, p . 153. 5. Foster, J . H., Killen, D. A., Diveley, W. L., MeCracken, R. L., and Hubbard, W. W.: Pulmonary Resection in the Treatment of Tuberculosis, Dis. Chest 40: 5, 1961. 6. Eldred, W. J., and Sampson, P . C : An Inquiry Into t h e Causes and Prevention of Com plications in Resection Surgery for Pulmonary Tuberculosis, J . THORACIC & CAR DIOVAS. SURG. 3 9 : 716,1960.
7. Floyd, R. D, Hollister, W F . , and Sealy, W. C : Complications in 430 Consecutive Pul monary Resections for Tuberculosis, Surg. Gynec. & Obst. 109: 467, 1959. 8. Gebauer, P . W., and Mason, C. B . : Analysis and Late Results of Resection for Pulmonary Tuberculosis in Hawaii, Am. Rev. Resp. Dis. 80: 6, 1959.
Vol. 46, No. 5
A T Y P I C A L MYCOBACTERIAL I N F E C T I O N S
November, 1963
701 '
V ±
9. Barrett, B . X , Neal, H . S., Day, J . C , Chapman, P . T., O'Eourke, P . V., O'Brien, E . J., and T u t t l e W. M.: Pulmonary Besection in t h e Treatment of Tuberculosis, J . THORACIC SURG. 36: 803, 1958.
10. Movvlem, A., Connolly, C. J., and Zimmerman, B . : The Surgical Treatment of Pulmonary Tuberculosis in the Mentally 111, Surgery 4 3 : 913, 1958. 11. Moore, J . A., Walkup, H . E., Bayl, J . E., and Chapman, J . P., J r . : E n d Eesults of Pul monary Besection for Tuberculosis, Ann. Surg. 147: 659, 1958. 12. Chofnas, I., and Newton, J . : Pneumonitis Due to Chromogenic Acid-Fast Bacilli in Trans actions of Fourteenth Conference on the Chemotherapy of Tuberculosis, Veterans Ad ministration-Army-Navy, Washington, D. C , 1955, Government Printing Office, p . 205. 13. Florence, H . : Atypical Acid-Fast (Chromogenic) Organisms Complicating Pulmonary Dis ease, Dis. Chest. 30: 250, 1956. 14. Crow, H . E., King, C. T., Smith, C. E., Corpe, B . F . , and Stergus, I . : A Limited Clin ical, Pathologic, and Epidemiologic Study of Patients With Pulmonary Lesions Associated With Atypical Acid-Fast Bacilli in the Sputum, Am. Bev. Tuberc. 7 5 : 199, 1957. 15. Taylor, A. J . : The Surgical Treatment of Patients With Infections of the Lung Due to Unclassified Acid-Fast Bacilli, Am. Bev. Besp. Dis. 83: 127, 1961. 16. Seiler, H . I I . : Pulmonary Besection in the Treatment of Atypical Myeobacterial Infec tions. Presented to Southern Thoracic Society, Hot Springs, Arkansas, Sept. 6-8, 1961. 17. Lester, W., J r . , Botkin, J., and Colton, B . : An Analysis of Forty-nine Cases of Pulmonary Disease Caused by Photochromogenic Mycobacteria in Transactions of Seventeenth Conference on Chemotherapy of Tuberculosis. Veterans Administration-Armed Forces, Washington, D. C , 1958, Government Printing Office, p . 289. 18. Harrison, B. W., Beimann, A. F . , Long, E. T., Lester, W., J r . , and Adams, W. E . : Adverse Surgical Experience in the Treatment of Pulmonary Disease Caused by Atypical Acid-Fast Bacilli, J . THORACIC & CARDIOVAS. SURG. 3 8 : 481, 1959.
(For Discussion, see page 713)