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Coccidioidal pulmonary cavities with rupture
J THORAC CARDIOVASC SURG 84: 172-177, 1982
Original Communications
Coccidioidal pulmonary cavities with rupture Twenty-three patients with spontaneous rupture of a pulmonary cavity with a pyopneumothorax resulting from coccidioidomycosis are presented. Clinical and laboratory findings, medical and surgical treatment, and complications are detailed. Skin tests are not helpful in making a diagnosis. Although complement fixation titers were elevated in all patients and cultures were positive in 21, these laboratory tests should not delay surgical treatment. Surgical treatment included seven lobectomies, thirteen partial lobectomies, and one pneumonectomy. Two patients did not undergo surgical resection. Seventeen required some degree of decortication. There were three major complications and no deaths. Prompt operation is recommended when the diagnosis is suspected. Reasons for postponement include delay in seeking treatment, poorly controlled diabetes, and other complicating medical factors. The extent of surgical resection may have to be limited because of the extensive contamination of the pleural space. Amphotericin B was administered in 10 patients. The drug should be administered when the cavity ruptures in the acute phase of the disease, in all patients with diabetes, in delayed operations, in patients with concomitant medical problems, and when the extent of resection is limited to obtain immediate obliteration of the pleural space.
R. T. Cunningham, M.D., Bakersfield, Calif., and Hans Einstein, M.D., Los Angeles, Calif.
Read at the Seventh Annual Meeting of The Samson Thoracic Surgical Society, Maui, Hawaii, June 24-27, 1981. Address for reprints: R. T. Cunningham, M.D., 2028 17th St., Bakersfield, Calif. 9330 I.
our private practice in Bakersfield, California. Age distribution of the patients ranged from 11 to 47 years, with the mean age being 24. There were 17 male and six female patients. Racial distribution included 19 Caucasians, two Orientals, and two Mexican-Americans. There were no Afro-Americans or Filipinos in the series. Coccidioidal infections are not well controlled in these specific racial groups and tend to disseminate rather than remain localized in pulmonary cavities. Seven of the 23 patients had an established history of coccidioidomycosis before the cavity ruptured. Of these seven, two were under observation for the acute phase at the time of rupture. The remaining five patients had also been diagnosed as having chronic cavitary coccidioidomycosis but were not under medical supervision at the time of rupture. The other 16 patients had no prior history of a coccidioidal infection nor was the presence of a cavity known before rupture occurred. Each case was reviewed individually, with the main focus being on management and treatment specifically related to the occurrence of a spontaneous rupture of a coccidioidal cavity (Table I). Follow-up was attempted on all cases by a mailed questionnaire.
172
0022-5223/82/080172+06$00.60/0
Considerable experience has been recorded in the literature regarding the incidence and treatment of pulmonary cavities resulting from coccidioidomycosis, but there is very little pertaining to the management and treatment of spontaneous rupture of those pulmonary cavities.!"" Because the diagnosis is difficult to recognize, proper surgical treatment is frequently delayed. Surgical management differs from that of other pulmonary coccidioidal cavities and amphotericin B is used more frequently. We will relate in this paper 25 years' experience with the sequelae of pulmonary coccidioidomycosis in 23 related cases of ruptured coccidioidal cavity. Patients From 1955 to 1980, 23 instances of spontaneous rupture of coccidioidomycosis cavities were observed in
© 1982 The'"C. V. Mosby Co.
Volume 84 Number 2 August, 1982
Coccidioidal pulmonary cavities
I73
Fig. 1. Chest roentgenogram of Patient 22 taken a few hours after the onset of symptoms of rupture . There is a significant amount of fluid, but no cavity is visible.
Fig. 2. Chest roentgenogram of Patient 9 taken 3 days after the onset of symptoms of rupture . There is a significant amount of fluid, but no cavity is visible.
Results
Treatment. Treatment for the patients consisted of closed chest drainage , surgical resection, decortication, administration of amphotericin B, or a combination of these . Only two of the patients were treated satisfactorily with intubation and closed chest drainage. The other 21 received some form of surgical resection depending on the extent and location of the ruptured cavity. In 14 the disease was localized enough to be managed by partial lobectomy. The other seven required lobectomies. One diabetic patient required pneumonectomy following multiple wedge resections. Indications for the use of amphotericin B are many in this circumstance. Ten patients were so treated. Three patients received the drug because of a long delay before operation, two because the rupture took place in the acute phase of the disease , and one patient with diabetes had active pulmonary tuberculosis at the time of rupture. Other reasons for the antifungal therapy in our group included closed chest drainage only, diabetes, postoperative bronchopleural fistula, and a high or rising complement fixation titer (> I : 64), indicating threatened extrapulmonary dissemination. When amphotericin B is started before the operation , the usual preoperative dose is 300 to 500 mg with completion of at least I gm total in the postoperative period . In some patients with diabetes or other compli cations, the dosage may exceed I gm. When administered only postoperatively, a minimum dose of I gm is recommended. Complications and treatments. Delays in surgical
Laboratory studies. The following laboratory studies and results were obtained on this group of patients (Table II): Cultures of the chest fluid were positive for Coccidioides immitis in 21 cases . Serologic tests were positive in all cases, with complement fixation titers ranging from I : 4 dilution and going as high as I: 256. Coccidioidin skin tests were available in only 15 patients. Of these, five were positive and IOnegative at a I : 100 dilution. The remaining eight patients had no documented skin test. Diagnosis. Rupture of a coccidioidomycosis cavity is not always obvious but must be considered in the differential diagnosis with the following history and abnormal x-ray findings. The patient will have had chest pain and shortness of breath, perhaps for a few days . Hemoptysis is rarely present. Usually, the patient will not be acutely ill and may have only a low-grade fever. A history of a coccidioidomycosis infection will be uncommon . Chest roentgenograms are not particularly useful in diagnosing coccidioidomycosis and are not likely to reveal a ruptured cavity . 5 . 6 The film may only show varying degrees of pneumothorax (Figs. I and 2). Suspicion should be aroused by a patient who has been in an endemic area and has a spontaneous pneumothorax with a significant amount of fluid developing in the pleural cavity over a few hours. fluid that is cloudy on aspiration or following intubation should further alert the clinician to the possible presence of a ruptured cavity.
The Journal of
1 74 Cunningham and Einstein
Thoracic and Cardiovascular Surgery
Table I. Composite chart of all patients History ofcocci.
Age (yr)
Sex
Race
I 2 3 4 5 6 7 8 9
27 16 17 II 15 24 30 24 47
F F F F M M M M M
Caucasian Caucasian Caucasian Caucasian Mexican- American Caucasian Caucasian Mexican-American Caucasian
Yes No No No No No No No Yes
10
47
F
Caucasian
II 12 13 14 15 16 17 18 19 20
22 27 43 31 26 18 29 19 19 16
M M M M M M M M M M
21 22
24 II
23
38
Case
Skin test
Culture
Serology
Resection
Positive Negative Negative Negative Negative Positive Negative
Positive Positive Positive Positive Negative Positive Positive Negative Positive
1:8 1:256 1:32 I: 16 I: 16 I: 16 1:4 I: 16 I: 16
Lobectomy Lobectomy Intubation only Partial lobectomy Partial lobectomy Partial lobectomy Lobectomy Intubation only Pneumonectomy
No
Negative
Positive
I: 128
Partial lobectomy
Caucasian Caucasian Caucasian Oriental Oriental Caucasian Caucasian Caucasian Caucasian Caucasian
Yes Yes No Yes Yes No No No No Yes
Positive Negative
Positive
Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive
I: 128 1:64 1:2 I: 16 1:4 1:8 1:2 1:32 1:32 1:32
Partial lobectomy Partial lobectomy Partial lobectomy Lobectomy Partial lobectomy Lobectomy Partial lobectomy Partial lobectomy Partial lobectomy Lobectomy
M F
Caucasian Caucasian
No Yes
Positive
Positive Positive
1:4 I: 128
Partial lobectomy Lobectomy
M
Caucasian
No
Positive
1:4
Partial lobectomy
Negative Negative Negative
Legend: RUL, Right upper lobe. RLL, Right lower lobe. LLL, Left lower lobe. LUL, Left upper lobe. BPF, Bronchopleural fistula. TB, Tuberculosis.
Table II. Laboratory studies No. ofcases Cultures Positive Negative Complement fixation titers I: 16 or less I: 64 or less Over 1:64 Skin tests Positive Negative Unavailable
21 2 14
5 4 5 10
8
treatment and pre-existmg medical conditions accounted for the majority of problems in management and complications. The surgical complications were two bronchopleural fistulas and a recurrent cavity. Three patients had had chest tubes inserted by their
local physicians and were first seen 6 weeks later because the bronchopleural fistula failed to close and the lung did not re-expand. They all received preoperative amphotericin treatment prior to decortication with resection. The antifungal treatment was then continued postoperatively. One patient had mild diabetes and active pulmonary tuberculosis. She was treated by chest intubation with suction while her condition was stabilized. Thirty-two days later the fistula was still open. The patient then underwent wedge resection and extensive decortication. Another diabetic patient originally treated conservatively with intubation and amphotericin B was finally operated upon because the fistula failed to close after 35 days. Cavities were removed from both the upper and lower lobes of the left lung. He returned later with a bronchopleural fistula and empyema that necessitated pneumonectomy and window drainage. Even with these extenuating circumstances, there were no deaths from rupture of the coccidioidomycosis cavities.
Volume 84
Coccidioidal pulmonary cavities
Number 2
August. 1982
Decortication
Amphotericin B Preop.
Yes Yes
I
Postop.
Days to operation
Location of lesion
Yes Yes
60 9
Yes
Yes
Yes Yes
35
RUL RLL LLL RLL LLL RLL LLL LLL LUL,LLL
Yes
Yes
Yes
32
LLL
Yes
Yes
Yes
60 4
RLL RLL LUL RUL RLL LLL LLL LUL RUL RLL
Yes
6 10 8 5
Yes
Yes
Yes
Yes Yes Yes Yes Yes
Yes
Yes
Yes
II 18 8 19 50 75 15 5
Yes
Yes
Yes
3 5
LLL LLL
40
LUL
Yes
Discussion
Our experiences indicate that patients with ruptured pulmonary cavities should have definitive operation as soon as the diagnosis is suspected. Pulmonary cavities resulting from coccidioidomycosis have a bronchial communication but are located in the intersegmental plane, sometimes crossing the major fissure. We have found that they are not amenable to single segmental resection but are best handled by wedge, multiple segmentectomy, lobectomy, or a combination of these procedures. Delays in surgical correction result in chronic fistulas and extensive fibrinothorax. Seventeen of our patients required varying degrees of decortication, and the thickness of and difficulty in removing the peel were directly related to the duration of the fistula. The need for decortication further contributes to the difficulty in re-expansion of the remaining lung and obliteration of the pleural space. Therefore, we tend to limit the extent of the resection. Consequently, total lobectomy, as rec-
17 5
Comments Postop. BPF
Postop. BPF and diabetes Active TB and diabetes
Ruptured cavity, acute phase Ruptured cavity, acute phase Wedge, recurrent cavity 4 yr later
ommended by some, is not always advisable as in elective operations. 7 The lack of a history of a coccidioidomycosis infection in patients who have a pulmonary cavity is substantiated by our series, for only seven of the 23 patients were aware of the infection. Skin tests are frequently negative in cavitary disease, as previously illustrated, and the clinician should not ignore the possibility of a ruptured cavity. In our series only five of 15 patients had positive skin tests. Complement fixation titers, as a rule, were low and only four were positive in over the 1: 64 dilution. These factors are considered, by some, to indicate a poor immunologic response by the patient and probably suggest a poor prognosis. 8 We do not believe that routine administration of amphotericin B is indicated in the patient with well-controlled disease and a ruptured cavity who receives early surgical treatment. Similarly, we seldom use amphotericin B therapy in elective operations for nonruptured coccidioidomycosis cavities. t Amphotericin B should
The Journal of
I 7 6 Cunningham and Einstein
be given preoperatively and postoperatively if there is a delay in coming to operation. When the operation is performed without delay, amphotericin B is administered only postoperatively when indicated. Indications for postoperative therapy include bronchopleural fistula, rupture in the acute phase, suspected residual disease, diabetes, active contralateral disease, and concomitant medical problems. Elevation of the complement fixation titer alone was not used as an indication for amphotericin B therapy. In our series the four patients who had titers over the I: 64 dilution received amphotericin B and had a specific medical or surgical indication. The specific indicators were delay in coming to operation, concomitant active pulmonary tuberculosis, rupture in the acute phase of the disease, and postoperative bronchopleural fistula. Amphotericin B is the only antifungal drug that we have used, and we have found it successful as an adjunctive therapy in the treatment of ruptured coccidioidomycosis cavities.
2
3
4 5 6 7
8
REFERENCES Fosburg RG, Baisch BF, Trummer MJ: Limited pulmonary resection for coccidioidomycosis. Ann Thorac Surg 7: 420-427, 1969 Rivkin LM, Winn DE, Salyer JM: The surgical treatment of pulmonary coccidioidomycosis. J THoRAc CARDIOVASC SURG 42:402-412, 1961 Winn WA: A long term study of 300 patients with cavitary abscess lesions of the lung of coccidioidal origin. Chest 54:Suppl I: 12-16, 1968 Dratz OJ, Catanzaro A: State of the art. Coccidioidomycosis: Part II. Am Rev Respir Dis 117:727-771, 1978 Birsner JW: The Roentgen aspects of 500 cases of pulmonary coccidioidomycosis. AJR 72:556-573, 1954 Jamison HW: A Roentgen study of chronic pulmonary coccidioidomycosis. AJR 55:396-412, 1946 Grant AR, Mellick OW: The surgical treatment of cavitary pulmonary coccidioidomycosis. Arch Surg 94:559-570, 1967 Baker EJ, Hawkins JA, Waskow EA: Surgery for coccidioidomycosis in 52 diabetic patients with special reference to related immunologic factors. J THORAC CARDIOVASC SURG 75:680-687, 1978
Discussion DR. LOUIS DECARO Duarte, Calif.
I would like to ask Dr. Cunningham whether his group has used miconazole , a new drug in America with which there is about 5 years' experience for other types of internal mycosis in Europe. It produces less toxicity than amphotericin B.
Thoracic and Cardiovascular
Surgery
DR. EARL J. BAKER Phoenix, Ariz.
Dr. Cunningham has given our Society a unique review. I know of no prior presentation on this important subject. High points include culture of chest fluid for fungus and use of coccidioidal serology for diagnosis in the patient from an endemic area presenting with a pyopneumothorax. Early operation with obliteration of any residual pleural space is recommended. The zero mortality reported by Dr. Cunningham in this difficult patient group supports these tenets. Coccidioidomycosis is a disease of varied immunologic disaster. [Slide] The immunocompromising factors of male sex, age over 40 years, dark-skinned race, use of steroids, presence of lymphoid disease, pregnancy, and, most important, inadequate resection, are noted in this slide of 29 surgically treated, diabetic patients with coccidioidal cavitary disease. I suspect that, as in lung cancer, the proper use of debulking has a relationship to coccidioidomycosis, in that maximum disease extirpation is a direct aid to total host defense mechanisms. Thus we begin to leam. [Slide] The mean total number of these compromising factors, when related to final postoperative patient status, was as follows: stable 1.25; complicated, 2.3; and death, 3.2. A negative skin test in the known coccidioidal patient is the hallmark of definite immunocompromise. In Dr. Cunningham's series, the known skin tests were positive in five cases and negative in ten. Eleven of the 17 patients with acute pyothorax were male. Two of the three complications were due to inadequate resection, and one of these (occurring in the only insulin-dependent diabetic patient) required pneumonectomy for cure. The co-association of these factors in Dr. Cunningham's patients suggest that acute coccidioidal cavity rupture may be considered a new and additional index of severe imrnunocompromise, thus demarcating the patient who will require maximum treatment for cure. Dr. Cunningham, should all peripheral cavities in the patient with negative skin tests be removed? Would use of a Miscall type pleural tent have allowed for a more total removal of disease with concomitant space obliteration? Finally, what are your thoughts regarding the present use of coccidioidal vaccine? DR. C U N N I N G HAM (Closing) Amphotericin is the only drug that I know is effective. Miconazole has been used and tried for quite a while, but I do not think it is effective. There is another new drug on the market, ketoconazole, that I understand has just been approved for use. It has been used on an experimental basis up to now. It is an oral medication, easy to give, but we do not know enough about it at this time to recommend it. In our area where it is being given, the patients are told they will have to continue taking the drug for the rest of their lives. I think it is better to treat them surgically than to have them taking medicine for that long. I appreciate Dr. Baker's comments and I understand his feelings. We all are concerned about peripheral cavities. Cer-
Volume 84 Number 2
Coccidioidal pulmonary cavities
177
August. 1982
tainly a peripheral cavity combined with a negative skin test would encourage me to push for surgical removal. You will notice in this series that the majority of these patients did not have the slightest knowledge that they had had Valley Fever up until the cavity ruptured. As far as using a pleural tent, we have stayed away from opening up uninfected planes. We have not been doing pleural tents or thoracoplasties at the time, because I do not know how virulent this empyema is, and I would hate to spread it around the chest wall. We do not have a good drug for its treatment.
We are conducting a vaccine program in our area, along with the University of Arizona at Tucson and the Lemoore Naval Base. This vaccine for coccidioidomycosis was developed by Dr. Levine at the Navy Laboratory, Oakland, and the University of California at Berkeley, along with Dr. Pappagianis at Davis. We are having to follow strict protocol, but we feel that it is an effective vaccine. I hope that in 3 years we will be able to market it. Already companies have approached Dr. Levine regarding the marketing of this vaccine when it is approved by the Food and Drug Administration.
Original Communications
Coccidioidal pulmonary cavities with rupture Twenty-three patients with spontaneous rupture of a pulmonary cavity with a pyopneumothorax resulting from coccidioidomycosis are presented. Clinical and laboratory findings, medical and surgical treatment, and complications are detailed. Skin tests are not helpful in making a diagnosis. Although complement fixation titers were elevated in all patients and cultures were positive in 21, these laboratory tests should not delay surgical treatment. Surgical treatment included seven lobectomies, thirteen partial lobectomies, and one pneumonectomy. Two patients did not undergo surgical resection. Seventeen required some degree of decortication. There were three major complications and no deaths. Prompt operation is recommended when the diagnosis is suspected. Reasons for postponement include delay in seeking treatment, poorly controlled diabetes, and other complicating medical factors. The extent of surgical resection may have to be limited because of the extensive contamination of the pleural space. Amphotericin B was administered in 10 patients. The drug should be administered when the cavity ruptures in the acute phase of the disease, in all patients with diabetes, in delayed operations, in patients with concomitant medical problems, and when the extent of resection is limited to obtain immediate obliteration of the pleural space.
R. T. Cunningham, M.D., Bakersfield, Calif., and Hans Einstein, M.D., Los Angeles, Calif.
Read at the Seventh Annual Meeting of The Samson Thoracic Surgical Society, Maui, Hawaii, June 24-27, 1981. Address for reprints: R. T. Cunningham, M.D., 2028 17th St., Bakersfield, Calif. 9330 I.
our private practice in Bakersfield, California. Age distribution of the patients ranged from 11 to 47 years, with the mean age being 24. There were 17 male and six female patients. Racial distribution included 19 Caucasians, two Orientals, and two Mexican-Americans. There were no Afro-Americans or Filipinos in the series. Coccidioidal infections are not well controlled in these specific racial groups and tend to disseminate rather than remain localized in pulmonary cavities. Seven of the 23 patients had an established history of coccidioidomycosis before the cavity ruptured. Of these seven, two were under observation for the acute phase at the time of rupture. The remaining five patients had also been diagnosed as having chronic cavitary coccidioidomycosis but were not under medical supervision at the time of rupture. The other 16 patients had no prior history of a coccidioidal infection nor was the presence of a cavity known before rupture occurred. Each case was reviewed individually, with the main focus being on management and treatment specifically related to the occurrence of a spontaneous rupture of a coccidioidal cavity (Table I). Follow-up was attempted on all cases by a mailed questionnaire.
172
0022-5223/82/080172+06$00.60/0
Considerable experience has been recorded in the literature regarding the incidence and treatment of pulmonary cavities resulting from coccidioidomycosis, but there is very little pertaining to the management and treatment of spontaneous rupture of those pulmonary cavities.!"" Because the diagnosis is difficult to recognize, proper surgical treatment is frequently delayed. Surgical management differs from that of other pulmonary coccidioidal cavities and amphotericin B is used more frequently. We will relate in this paper 25 years' experience with the sequelae of pulmonary coccidioidomycosis in 23 related cases of ruptured coccidioidal cavity. Patients From 1955 to 1980, 23 instances of spontaneous rupture of coccidioidomycosis cavities were observed in
© 1982 The'"C. V. Mosby Co.
Volume 84 Number 2 August, 1982
Coccidioidal pulmonary cavities
I73
Fig. 1. Chest roentgenogram of Patient 22 taken a few hours after the onset of symptoms of rupture . There is a significant amount of fluid, but no cavity is visible.
Fig. 2. Chest roentgenogram of Patient 9 taken 3 days after the onset of symptoms of rupture . There is a significant amount of fluid, but no cavity is visible.
Results
Treatment. Treatment for the patients consisted of closed chest drainage , surgical resection, decortication, administration of amphotericin B, or a combination of these . Only two of the patients were treated satisfactorily with intubation and closed chest drainage. The other 21 received some form of surgical resection depending on the extent and location of the ruptured cavity. In 14 the disease was localized enough to be managed by partial lobectomy. The other seven required lobectomies. One diabetic patient required pneumonectomy following multiple wedge resections. Indications for the use of amphotericin B are many in this circumstance. Ten patients were so treated. Three patients received the drug because of a long delay before operation, two because the rupture took place in the acute phase of the disease , and one patient with diabetes had active pulmonary tuberculosis at the time of rupture. Other reasons for the antifungal therapy in our group included closed chest drainage only, diabetes, postoperative bronchopleural fistula, and a high or rising complement fixation titer (> I : 64), indicating threatened extrapulmonary dissemination. When amphotericin B is started before the operation , the usual preoperative dose is 300 to 500 mg with completion of at least I gm total in the postoperative period . In some patients with diabetes or other compli cations, the dosage may exceed I gm. When administered only postoperatively, a minimum dose of I gm is recommended. Complications and treatments. Delays in surgical
Laboratory studies. The following laboratory studies and results were obtained on this group of patients (Table II): Cultures of the chest fluid were positive for Coccidioides immitis in 21 cases . Serologic tests were positive in all cases, with complement fixation titers ranging from I : 4 dilution and going as high as I: 256. Coccidioidin skin tests were available in only 15 patients. Of these, five were positive and IOnegative at a I : 100 dilution. The remaining eight patients had no documented skin test. Diagnosis. Rupture of a coccidioidomycosis cavity is not always obvious but must be considered in the differential diagnosis with the following history and abnormal x-ray findings. The patient will have had chest pain and shortness of breath, perhaps for a few days . Hemoptysis is rarely present. Usually, the patient will not be acutely ill and may have only a low-grade fever. A history of a coccidioidomycosis infection will be uncommon . Chest roentgenograms are not particularly useful in diagnosing coccidioidomycosis and are not likely to reveal a ruptured cavity . 5 . 6 The film may only show varying degrees of pneumothorax (Figs. I and 2). Suspicion should be aroused by a patient who has been in an endemic area and has a spontaneous pneumothorax with a significant amount of fluid developing in the pleural cavity over a few hours. fluid that is cloudy on aspiration or following intubation should further alert the clinician to the possible presence of a ruptured cavity.
The Journal of
1 74 Cunningham and Einstein
Thoracic and Cardiovascular Surgery
Table I. Composite chart of all patients History ofcocci.
Age (yr)
Sex
Race
I 2 3 4 5 6 7 8 9
27 16 17 II 15 24 30 24 47
F F F F M M M M M
Caucasian Caucasian Caucasian Caucasian Mexican- American Caucasian Caucasian Mexican-American Caucasian
Yes No No No No No No No Yes
10
47
F
Caucasian
II 12 13 14 15 16 17 18 19 20
22 27 43 31 26 18 29 19 19 16
M M M M M M M M M M
21 22
24 II
23
38
Case
Skin test
Culture
Serology
Resection
Positive Negative Negative Negative Negative Positive Negative
Positive Positive Positive Positive Negative Positive Positive Negative Positive
1:8 1:256 1:32 I: 16 I: 16 I: 16 1:4 I: 16 I: 16
Lobectomy Lobectomy Intubation only Partial lobectomy Partial lobectomy Partial lobectomy Lobectomy Intubation only Pneumonectomy
No
Negative
Positive
I: 128
Partial lobectomy
Caucasian Caucasian Caucasian Oriental Oriental Caucasian Caucasian Caucasian Caucasian Caucasian
Yes Yes No Yes Yes No No No No Yes
Positive Negative
Positive
Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive
I: 128 1:64 1:2 I: 16 1:4 1:8 1:2 1:32 1:32 1:32
Partial lobectomy Partial lobectomy Partial lobectomy Lobectomy Partial lobectomy Lobectomy Partial lobectomy Partial lobectomy Partial lobectomy Lobectomy
M F
Caucasian Caucasian
No Yes
Positive
Positive Positive
1:4 I: 128
Partial lobectomy Lobectomy
M
Caucasian
No
Positive
1:4
Partial lobectomy
Negative Negative Negative
Legend: RUL, Right upper lobe. RLL, Right lower lobe. LLL, Left lower lobe. LUL, Left upper lobe. BPF, Bronchopleural fistula. TB, Tuberculosis.
Table II. Laboratory studies No. ofcases Cultures Positive Negative Complement fixation titers I: 16 or less I: 64 or less Over 1:64 Skin tests Positive Negative Unavailable
21 2 14
5 4 5 10
8
treatment and pre-existmg medical conditions accounted for the majority of problems in management and complications. The surgical complications were two bronchopleural fistulas and a recurrent cavity. Three patients had had chest tubes inserted by their
local physicians and were first seen 6 weeks later because the bronchopleural fistula failed to close and the lung did not re-expand. They all received preoperative amphotericin treatment prior to decortication with resection. The antifungal treatment was then continued postoperatively. One patient had mild diabetes and active pulmonary tuberculosis. She was treated by chest intubation with suction while her condition was stabilized. Thirty-two days later the fistula was still open. The patient then underwent wedge resection and extensive decortication. Another diabetic patient originally treated conservatively with intubation and amphotericin B was finally operated upon because the fistula failed to close after 35 days. Cavities were removed from both the upper and lower lobes of the left lung. He returned later with a bronchopleural fistula and empyema that necessitated pneumonectomy and window drainage. Even with these extenuating circumstances, there were no deaths from rupture of the coccidioidomycosis cavities.
Volume 84
Coccidioidal pulmonary cavities
Number 2
August. 1982
Decortication
Amphotericin B Preop.
Yes Yes
I
Postop.
Days to operation
Location of lesion
Yes Yes
60 9
Yes
Yes
Yes Yes
35
RUL RLL LLL RLL LLL RLL LLL LLL LUL,LLL
Yes
Yes
Yes
32
LLL
Yes
Yes
Yes
60 4
RLL RLL LUL RUL RLL LLL LLL LUL RUL RLL
Yes
6 10 8 5
Yes
Yes
Yes
Yes Yes Yes Yes Yes
Yes
Yes
Yes
II 18 8 19 50 75 15 5
Yes
Yes
Yes
3 5
LLL LLL
40
LUL
Yes
Discussion
Our experiences indicate that patients with ruptured pulmonary cavities should have definitive operation as soon as the diagnosis is suspected. Pulmonary cavities resulting from coccidioidomycosis have a bronchial communication but are located in the intersegmental plane, sometimes crossing the major fissure. We have found that they are not amenable to single segmental resection but are best handled by wedge, multiple segmentectomy, lobectomy, or a combination of these procedures. Delays in surgical correction result in chronic fistulas and extensive fibrinothorax. Seventeen of our patients required varying degrees of decortication, and the thickness of and difficulty in removing the peel were directly related to the duration of the fistula. The need for decortication further contributes to the difficulty in re-expansion of the remaining lung and obliteration of the pleural space. Therefore, we tend to limit the extent of the resection. Consequently, total lobectomy, as rec-
17 5
Comments Postop. BPF
Postop. BPF and diabetes Active TB and diabetes
Ruptured cavity, acute phase Ruptured cavity, acute phase Wedge, recurrent cavity 4 yr later
ommended by some, is not always advisable as in elective operations. 7 The lack of a history of a coccidioidomycosis infection in patients who have a pulmonary cavity is substantiated by our series, for only seven of the 23 patients were aware of the infection. Skin tests are frequently negative in cavitary disease, as previously illustrated, and the clinician should not ignore the possibility of a ruptured cavity. In our series only five of 15 patients had positive skin tests. Complement fixation titers, as a rule, were low and only four were positive in over the 1: 64 dilution. These factors are considered, by some, to indicate a poor immunologic response by the patient and probably suggest a poor prognosis. 8 We do not believe that routine administration of amphotericin B is indicated in the patient with well-controlled disease and a ruptured cavity who receives early surgical treatment. Similarly, we seldom use amphotericin B therapy in elective operations for nonruptured coccidioidomycosis cavities. t Amphotericin B should
The Journal of
I 7 6 Cunningham and Einstein
be given preoperatively and postoperatively if there is a delay in coming to operation. When the operation is performed without delay, amphotericin B is administered only postoperatively when indicated. Indications for postoperative therapy include bronchopleural fistula, rupture in the acute phase, suspected residual disease, diabetes, active contralateral disease, and concomitant medical problems. Elevation of the complement fixation titer alone was not used as an indication for amphotericin B therapy. In our series the four patients who had titers over the I: 64 dilution received amphotericin B and had a specific medical or surgical indication. The specific indicators were delay in coming to operation, concomitant active pulmonary tuberculosis, rupture in the acute phase of the disease, and postoperative bronchopleural fistula. Amphotericin B is the only antifungal drug that we have used, and we have found it successful as an adjunctive therapy in the treatment of ruptured coccidioidomycosis cavities.
2
3
4 5 6 7
8
REFERENCES Fosburg RG, Baisch BF, Trummer MJ: Limited pulmonary resection for coccidioidomycosis. Ann Thorac Surg 7: 420-427, 1969 Rivkin LM, Winn DE, Salyer JM: The surgical treatment of pulmonary coccidioidomycosis. J THoRAc CARDIOVASC SURG 42:402-412, 1961 Winn WA: A long term study of 300 patients with cavitary abscess lesions of the lung of coccidioidal origin. Chest 54:Suppl I: 12-16, 1968 Dratz OJ, Catanzaro A: State of the art. Coccidioidomycosis: Part II. Am Rev Respir Dis 117:727-771, 1978 Birsner JW: The Roentgen aspects of 500 cases of pulmonary coccidioidomycosis. AJR 72:556-573, 1954 Jamison HW: A Roentgen study of chronic pulmonary coccidioidomycosis. AJR 55:396-412, 1946 Grant AR, Mellick OW: The surgical treatment of cavitary pulmonary coccidioidomycosis. Arch Surg 94:559-570, 1967 Baker EJ, Hawkins JA, Waskow EA: Surgery for coccidioidomycosis in 52 diabetic patients with special reference to related immunologic factors. J THORAC CARDIOVASC SURG 75:680-687, 1978
Discussion DR. LOUIS DECARO Duarte, Calif.
I would like to ask Dr. Cunningham whether his group has used miconazole , a new drug in America with which there is about 5 years' experience for other types of internal mycosis in Europe. It produces less toxicity than amphotericin B.
Thoracic and Cardiovascular
Surgery
DR. EARL J. BAKER Phoenix, Ariz.
Dr. Cunningham has given our Society a unique review. I know of no prior presentation on this important subject. High points include culture of chest fluid for fungus and use of coccidioidal serology for diagnosis in the patient from an endemic area presenting with a pyopneumothorax. Early operation with obliteration of any residual pleural space is recommended. The zero mortality reported by Dr. Cunningham in this difficult patient group supports these tenets. Coccidioidomycosis is a disease of varied immunologic disaster. [Slide] The immunocompromising factors of male sex, age over 40 years, dark-skinned race, use of steroids, presence of lymphoid disease, pregnancy, and, most important, inadequate resection, are noted in this slide of 29 surgically treated, diabetic patients with coccidioidal cavitary disease. I suspect that, as in lung cancer, the proper use of debulking has a relationship to coccidioidomycosis, in that maximum disease extirpation is a direct aid to total host defense mechanisms. Thus we begin to leam. [Slide] The mean total number of these compromising factors, when related to final postoperative patient status, was as follows: stable 1.25; complicated, 2.3; and death, 3.2. A negative skin test in the known coccidioidal patient is the hallmark of definite immunocompromise. In Dr. Cunningham's series, the known skin tests were positive in five cases and negative in ten. Eleven of the 17 patients with acute pyothorax were male. Two of the three complications were due to inadequate resection, and one of these (occurring in the only insulin-dependent diabetic patient) required pneumonectomy for cure. The co-association of these factors in Dr. Cunningham's patients suggest that acute coccidioidal cavity rupture may be considered a new and additional index of severe imrnunocompromise, thus demarcating the patient who will require maximum treatment for cure. Dr. Cunningham, should all peripheral cavities in the patient with negative skin tests be removed? Would use of a Miscall type pleural tent have allowed for a more total removal of disease with concomitant space obliteration? Finally, what are your thoughts regarding the present use of coccidioidal vaccine? DR. C U N N I N G HAM (Closing) Amphotericin is the only drug that I know is effective. Miconazole has been used and tried for quite a while, but I do not think it is effective. There is another new drug on the market, ketoconazole, that I understand has just been approved for use. It has been used on an experimental basis up to now. It is an oral medication, easy to give, but we do not know enough about it at this time to recommend it. In our area where it is being given, the patients are told they will have to continue taking the drug for the rest of their lives. I think it is better to treat them surgically than to have them taking medicine for that long. I appreciate Dr. Baker's comments and I understand his feelings. We all are concerned about peripheral cavities. Cer-
Volume 84 Number 2
Coccidioidal pulmonary cavities
177
August. 1982
tainly a peripheral cavity combined with a negative skin test would encourage me to push for surgical removal. You will notice in this series that the majority of these patients did not have the slightest knowledge that they had had Valley Fever up until the cavity ruptured. As far as using a pleural tent, we have stayed away from opening up uninfected planes. We have not been doing pleural tents or thoracoplasties at the time, because I do not know how virulent this empyema is, and I would hate to spread it around the chest wall. We do not have a good drug for its treatment.
We are conducting a vaccine program in our area, along with the University of Arizona at Tucson and the Lemoore Naval Base. This vaccine for coccidioidomycosis was developed by Dr. Levine at the Navy Laboratory, Oakland, and the University of California at Berkeley, along with Dr. Pappagianis at Davis. We are having to follow strict protocol, but we feel that it is an effective vaccine. I hope that in 3 years we will be able to market it. Already companies have approached Dr. Levine regarding the marketing of this vaccine when it is approved by the Food and Drug Administration.