- Email: [email protected]
The role and results of surgery in the management of chronic pulmonary histoplasmosis
The role and results of surgery in the management of chronic pulmonary histoplasmosis One hundred fifty-five patients with pulmonary histoplasmosis were operated upon at the Missouri State Chest Hospital over a 20 year period. The clinical manifestations, management, and immediate and long-term results were analyzed. Thirty-four out of 38 patients with focal histoplasmomas had wedge resection without amphotericin B. Their postoperatiive courses were benign. Lobectomy was the commonest procedure among 23 patients with pulmonary infiltration and 92 patients with cavitary disease. The purpose of surgery is usually to remove the residual localized lesion and focus of infection. Amphotericin B therapy in addition to surgery further decreased the incidence of late death and progression of the disease. Postoperative complications, however, were more frequent in patients with cavitary disease who received the drug.
Salim B. Saab, M.D., * Ruben Ungaro, M.D., ** and Carl Almond, M.D., *** Columbia and Mt. Vernon, Mo.
HistOPlasma capsulatum was first described and named by Darling ' in 1906, but it was not until 1934 that its identity as a specific fungus was established." Information has been accumulating over the past two decades about the epidemiology, clinical manifestations, natural history, and prognosis of histoplasmosis. Its protean manifestations have been emphasized. The disease has the capacity of involving one organ, usually the lung, or multiple organs. Significant progress has been achieved in the development of diagnostic tests and improved laboratory methods, as well as in treatment of the infection. However, surgical intervention is still required in a good Received for publication March I, 1974. • Assistant Professor of Surgery, University of Missouri Medical Center, Columbia, Missouri, and Associate Chief of Surgery, Missouri State Chest Hospital, Mt. Vernon, Mo. "Resident in Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo., and Missouri State Chest Hospital, Mt. Vernon, Mo . •• • Professor of Surgery and Chief, Section of Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo. 65201.
number of patients for diagnostic and/or therapeutic purposes. The purpose of this paper is to review the experience with 155 patients on whom major thoracic surgical procedures were performed at the Missouri State Chest Hospital in Mt. Vernon, Missouri, over a 20 year period.
Clinical material and methods Between July, 1953, and June, 1973, 155 patients with pulmonary histoplasmosis required thoracic surgical operations at this hospital. The diagnosis was confirmed in all except the only infant in the group by growing the organism in cultures and/or identifying it in tissue specimens. Of the 155 patients, 106 (68 per cent) were male and 49 (32 per cent) were female. Seventy-eight patients (50 per cent) were farmers or had lived on a farm. The age range was 10 months to 75 years, with a peak incidence at 40 to 59 years (49 per cent) (Table I). Symptoms. Twenty-four patients (16 per 159
The Journol of
160
Saab, Ungaro, Almond
Thoracic and Cardiovascular Surgery
Table I. Age Patients Decade
No.
%
~ 9 10-19 20-29 30-39 40-49 50-59 60-69 70-79
2 7 18 24 33 43 24 4 155
1 5 12 15 21 28 15 3 100
Totals
Table II. Symptoms Patients
Asymptomatic Symptomatic Cough Chest pain Fever Weight loss Dyspnea Fatigue Hemoptysis
No.
%
24
16 84 63 43 36 35 33 32 23
131
97 67 55 54 51 49 36
cent) were asymptomatic but were hospitalized because of abnormal findings on chest x-ray examination. The main symptoms in the remaining 131 patients (84 per cent) are listed in Table II. Diagnostic studies. The diagnostic studies are summarized in Table III. Fifty per cent had a positive reaction to the purified protein derivative (P.P.D.), while 78 per cent had a positive histoplasmin skin test. Both tests were positive in 61 patients (40 per cent), whereas in 60 patients (39 per cent) the histoplasmin test was positive but the tuberculin skin test negative. In 15 patients (10 per cent) the histoplasmin skin test was negative and the P.P.D. positive. The complement fixation test was positive in 54 per cent. Both complement fixation and histoplasmin skin tests were positive in 46 per cent and negative in 8 per cent. The skin test was positive but the complement
fixation test negative in 30 per cent, whereas 8 per cent had a negative skin test with a positive complement fixation test. Sputum cultures grew Histoplasma capsulatum in only 48 patients (31 per cent). Forty-five of these had cavitary histoplasmosis and 3 had pulmonary infiltration. None of the patients with coin lesion had a positive sputum culture. The diagnosis was confirmed by histopathological study in 141 patients (91 per cent). Among 78 bronchoscopies performed, 11 yielded some positive information (7 per cent): Evidence of endobronchial disease was discovered in 4 patients, and biopsy revealed squamous cell carcinoma in another 4. The source of bleeding was identified as the right upper lobe in 2, and stenosis of the left upper lobe bronchus was found in I patient. Bronchograms were done on 16 patients. Of these studies, 5 revealed bronchiectasis and 1 showed stenosis of the right middle lobe bronchus. Pulmonary function tests indicated respiratory impairment in 36 patients (23 per cent). In 21 of these the impairment was obstructive in nature, in 6 it was restrictive, and in 9 it was mixed. Table IV summarizes the radiologic appearance and lobar involvement. Thirtyeight patients (25 per cent) had a solitary, unilateral pulmonary nodule (coin lesion). The lesion showed as a pulmonary infiltrate in 23 patients (15 per cent), bilateral in 7. Ninety-two patients (59 per cent) had a cavitary lesion, unilateral in 65, and bilateral in 27. Two patients presented with a right hilar mass. Except in patients with coin lesion, the upper lobes were most frequently involved. The right upper lobe was involved in 87 patients and the left upper lobe in 69. Associated diseases. Sixty-seven patients (43 per cent) had one or more diseases in addition to pulmonary histoplasmosis (Table V). Pulmonary tuberculosis was present in 22 patients (14 per cent), emphy-
Volume 68
Chronic pulmonary histoplasmosis
Number 1
16 1
July. 1974
Table III. Diagnostic tests Positive Test
P.P.D. Histoplasmin skin test Complement fixation Sputum culture Histopathology Bronchoscopy Bronchogram Pulmonary function tests
Negative
Not done
No.
%
No.
%
No.
77
50 78 54 31 91 7 4 23
77
50 19 37 69 8 43 6 66
1 4 14
121 84 48 141 II
6 36
30 57 107 13 67 IO
102
I I 77
139 17
%
3 9 1 I
50 90 I1
Legend: P.P.D., Purified protein derivative.
Table IV. Radiographic localization by type of lesion Type oj lesion
Coin lesion
Unilateral Bilateral RUL RML RLL LUL LLL Totals
38 0 7 0 7 9 15 38
Cavitary disease
Pulmonary infiltrate
Right hilar mass
65 27 68 17
16 7 12 4 6
2 0
13
49 7 92
II
5 23
2
Totals
121 34 87 21 26 69 27 155
Legend: RUL, Right upper lobe. RML, Right middle lobe. RLL, Right lower lobe. LUL, Left upper lobe. LLL, Left lower lobe.
serna in 15, and bronchogenic carcinoma in II patients. Results A total of 174 thoracic surgical procedures were performed on 155 patients. The 19 reoperations were done on 18 patients. In 5 of these the indication was recurrence or progression of the disease, and in 13 it was to treat complications: Six thoracoplasties were done to obliterate an apical space, and 6 were for postresection bronchopleural fistula. One patient required pleurectomy for empyema. Eight patients were lost to follow-up but were in improved condition at the time of discharge, The remaining 147 patients were followed for 2 months to 13 years, with an average of 48 months. Among 20 late deaths, the cause of death was not known in 2. Only 5 patients died because of progression of the disease, whereas 8 patients died
of bronchogenic carcinoma. The cause of death was pneumonia in 2, emphysema in 1, pulmonary embolism in 1, and acute monocytic leukemia in 1. Twenty-eight patients (18 per cent) developed complications in the immediate postoperative period. Tables VI to IX summarize the indications for surgery, the primary thoracic operations, the postoperative complications, and the long-term results in the entire group. Coin lesions. Thirty-eight patients belonged to this category. Wedge resection was done in 34, lobectomy in 3, and pneumonectomy in 1. The indication for surgery was to obtain a definite diagnosis and rule out neoplasm in 35, Of these, 1 patient had a Class IV sputum cytology, with a 2.5 em. nodule in the right lower lobe, but pathological study of the excised nodule showed no cancer. The patient is doing well 2 years postoperatively, Lobectomy in another pa-
1 62
The Journal of Thoracic and Cardiovascular
Saab, Ungaro, Almond
Surgery
Table VI. Indications for surgery
Table V. Associated diseases Type of disease
No.
Pulmonary tuberculosis Pulmonary emphysema Bronchogenic carcinoma Cardiac disease Aspergillosis Diabetes mellitus Peptic ulcer Liver cirrhosis Chronic brain syndrome Hypertension Cholelithiasis Pneumothorax with cystic lung disease Bronchial asthma Interstitial pneumonitis Malignant lymphoma Fibrosarcoma of chest wall Herniated cervical disc Total
22 15 11 5 4 4 2 2 2 2 2 1 1 I I 1 I 77
tient revealed carcinoma in situ of the left upper lobe in addition to the histoplasmoma. He is doing well 1 year after operation. Of the remaining 3 patients, 1 required a pneumonectomy for squamous cell carcinoma of the left main-stem bronchus diagnosed by bronchoscopy and associated with a histoplasmoma. The patient is free of recurrence 2 years after operation. The second patient had a Histoplasma granuloma in the left lower lobe, with spontaneous pneumothorax secondary to cystic disease in the left upper lobe. Wedge resection of the nodule was performed, with excision of the cystic lesion. The third patient presented with left pleural effusion and a coin lesion in the left lower lobe. Pleural biopsy was not diagnostic, and two histoplasmomas were resected from the left upper and lower lobes at thoracotomy. The patient died 10 months later due to acute monocytic leukemia and cerebrovascular accident. This patient, plus 1 patient who died of pulmonary emphysema 9 years after wedge resection of a histoplasmoma, were the only ones in this group to die late after operation. Immediate postoperative complications included atelectasis, which responded to bronchoscopy and suctioning in 1 patient, and wound dehiscence, which was treated
Indication Coin lesion Pulmonary infiltration Unresolved Associated bronchiectasis Right middle lobe syndrome Associated cystic disease Persistent pleural effusion Diagnostic biopsy Associated carcinoma Associated tuberculosis Cavitary disease Resection of cavitary disease Destroyed lung Bronchiectasis Bronchopleural fistula Bronchial stenosis Associated carcinoma Associated tuberculosis Severe hemoptysis Right hilar mass (diagnostic)
No. 38 23 11 I I I I 3 3 2 92 61 7 5 3 I 6 7 2 2
by secondary closure in the only patient who had a pneumonectomy. None of the patients with coin lesion received amphotericin B, and none showed evidence of recurrence or progression of the disease. There were no late deaths related to histoplasmosis in this group. Pulmonary infiltration. This group included 23 patients. Lobectomy was done in 8, and wedge resection, segmental resection, and lung biopsy in 4 each. Two patients underwent pneumonectomy for associated bronchogenic carcinoma, and 1 patient required pleurectomy for persistent pleural effusion. An associated unresectable bronchogenic carcinoma was present in 1 patient who had lung biopsy. Eleven patients required surgery for unresolved pulmonary infiltrates and 2 for associated pulmonary tuberculosis. Bronchiectasis, right middle lobe syndrome, and cystic lung disease led to surgery in 1 patient each. Surgery was the only treatment in 15 patients. Postoperative complications occurred in 4 of these (27 per cent), and the disease progressed in 2 ( 13 per cent) . Eight patients had surgery plus amphoteri-
Volume 68
Chronic pulmonary histoplasmosis
Number 1
163
July, 1974
Table VII. Primary pulmonary operations Cavitary disease
Pulmonary infiltrate
Type of operation
Coin lesion
Wedge resection Segmental resection Lobectomy Lobectomy and wedge Pneumonectomy Thoracoplasty Lung biopsy Pleurectomy Hilar lymph node biopsy
34
1
4
0
0 3
19
4
0
48 10 9 4
7 1 2 0
I
4 I 0
0 0 0 0 0 0
0 1 0 0 0 0
0 0
Hilar mass
2
Table VIII. Immediate postoperative complications No.
Treatment
Persistent air space
Type of complication
6
Bronchopleural fistula Atelectasis
5
Pneumoperitoneum (2) Thoracoplasty (4) Thoracoplasty Bronchoscopy (4) Tracheostomy (1) Secondary closure Deroofing of space and antituberculosis therapy Anticoagulation Digitalis and diuretics Pleurectomy Tube drainage Conservative Conservative
Wound infection Loculated fluid with Mycobacterium tuberculosis Thrombophlebitis Pulmonary edema Empyema Pleural effusion Pericarditis Serum hepatitis
cin B. The latter was started preoperatively when the diagnosis was known and postoperatively when the diagnosis was established later. Only 1 patient (12 per cent) had a postoperative complication, and none had progression of the disease. There were no operative or late deaths due to histoplasmosis in patients with pulmonary infiltration. Hilar mass. Chest x-ray films in 2 patients showed a right hilar mass. These 2 patients were a 10-month-old girl, the youngest patient in the series, and a 16-year-old boy. In both, the P.P.D. skin tests and cultures for Histoplasma capsulatum and acid-fast bacilli were negative, but the histoplasmin skin tests and complement fixation tests were positive. Thoracotomy was recommended to confirm the suspected diagnosis. In the infant, biopsy of enlarged hilar lymph nodes showed a caseating granuloma. The
6 4
patient was given 60 mg. of amphotericin B postoperatively, although Histoplasma capsulatum was not identified by histopathology. The x-ray appearance and febrile course improved over 6 months of followup. In the second patient, pathological study of the hilar lymph node biopsy confirmed the diagnosis of histoplasmosis, and he was given a full course of amphotericin B postoperatively. He is doing well 3 years after the operation. Cavitary disease. Ninety-two patients, the largest number in this series, had chronic cavitary histoplasmosis. Fifty-eight patients had a lobectomy or lobectomy plus wedge resection, 19 patients had segmental resection, 9 required a pneumonectomy, and 1 had a wedge resection. Thoracoplasty was done in 4 patients-for bronchopleural fistula in 3 and for a destroyed lung in a patient with mixed impairment of pulmonary
The Journal of
164
Saab, Ungaro, Almond
Thoracic and Cardiovascular Surgery
Table IX. Total results over the follow-up period Type of lesion Coin lesion Surgery Surgery + ampho. B Infiltrate Surgery Surgery + ampho. B Cavitary disease Surgery Surgery + ampho. B Hilar mass Surgery Surgery + ampho. B Totals
I
IProgression
Postoperative complications
Operative deaths
0
2 0
0 0
0 0
0 0
15 8
4 1
0 0
0 0
0
44 48
7 14
2
3 2
11
0
0
0 0
0 0
0 0
0 0
28
2
5
17
Late deaths due to Histo.
No.
38
2 155
Late deaths due to Histu.
disease
of
2
4
Table X. Results in patients with cavitary histoplasmosis Mode of treatment Surgery + adequate ampho. B preop. Surgery + adequate ampho. B postop. Surgery + adequate ampho. B pre. and postop. Totals Surgery only Surgery + incomplete ampho. B
IProgression
No.
Postoperative complications
Operative deaths
12
5
o
9
3
o
18
4
o
39 44 9
12 7 2
o
1
2
2
3
11
1
2
function. Lung biopsy was done in 1 patient only, who was found to have an associated unresectable carcinoma. The most frequent indication for surgery in this group was resection of chronic cavitary histoplasmosis in 61 patients. Other indications included destroyed lung in 7, associated tuberculosis in 7, associated carcinoma in 6, bronchiectasis in 5, bronchopleural fistula in 3, severe hemoptysis in 2, and bronchial stenosis in 1 patient. Pneumonectomy was performed in 6 patients with destroyed lung and 3 patients with associated bronchogenic carcinoma. Of the 3 patients with bronchopleural fistula and empyema treated by thoracoplasty, 1 patient was lost to follow-up and the other 2 died 6 months and 3 years after operation due to progression of the disease.
o
I
disease
o
o
o
o
of
2
In 45 patients, the diagnosis was known preoperatively by positive sputum cultures. In 26 patients, the diagnosis was suspected because of the x-ray appearance with positive complement fixation tests and/or positive histoplasmin skin test and negative P.P.D. test. It was confirmed postoperatively by pathological study. The diagnosis was made postoperatively only, by positive pathological examination, in the remaining 21 patients. Forty-four patients had surgery only (Group A). Seven of these (16 per cent) developed complications and 2 died (4.4 per cent) in the postoperative period. There were 3 late deaths due to histoplasmosis (7 per cent), and 11 patients (25 per cent) exhibited progression of disease. The other 48 patients were treated by operation and
Volume 68 Number 1 July, 1974
administration of amphotericin B (Group B). Postoperative complications occurred in 14 (29 per cent), but there were no operative deaths. There were 2 late deaths due to histoplasmosis (4 per cent). Progression of the disease was documented in 4 patients (8 per cent). Further analysis of the results of surgery in patients with cavitary histoplasmosis in relation to amphotericin B therapy is shown in Table X. Nine patients in Group B did not receive the complete course of amphotericin B that is considered adequate. Adequate dosage is defined as 35 mg. per kilogram of body weight, or a total of around 2 Gm., administered intravenously over a period of around 16 weeks. Of the remaining 39 patients who had adequate amphotericin B therapy in the preoperative, postoperative, or both periods, 12 patients (3 I per cent) developed postoperative complications, with no operative deaths. The disease process progressed in 2 patients (5 per cent), and there was 1 late death due to histoplasmosis (2.5 per cent). Discussion It is estimated that half a million new Histoplasma capsulatum infections occur annually in the United States." Although the clinical manifestations of the disease cover a wide spectrum, three principal types have been recognized- 4: 1. The acute pulmonary form, which is an influenza-like illness, usually is selflimited but can progress to pneumonitis or form a primary complex simulating the Gohn complex of tuberculosis. It usually requires no treatment except in the occasional severe case with protracted course. 2. Disseminated histoplasmosis, acute or chronic, indicates hematogenous extrapulmonary spread and may resemble miliary tuberculosis. It may be fulminating in nature or may progress slowly over a period of years. Urgent medical treatment is required to prevent a usually fatal outcome." 3. Chronic pulmonary histoplasmosis may be the result of reactivation or progression of the primary infection or may represent
Chronic pulmonary histoplasmosis
165
an exogenous reinfection. It is the form most commonly encountered in practice and interests the thoracic surgeon because it requires medical and surgical treatment. A definite diagnosis of histoplasmosis is established only if the fungus is grown in cultures, usually of sputum or tissue specimen, or if it is identified in tissues by differential staining, usually with methenamine silver. Experience at the Missouri State Chest Hospital indicates that isolation of the organism is more successful in patients with chronic cavitary disease than in those with other types. Multiple specimens have to be processed, and animal inoculation should be resorted to at times. Sputum cultures give the best yield, whereas bronchial and gastric washings provide the poorest yield. The histoplasmin skin test determines delayed hypersensitivity to histoplasmosis, which is usually demonstrated in 2 weeks after exposure. Its use lies in defining endemic areas, but its value as a diagnostic tool is limited in several ways: False-positive and false-negative results do occur, as does cross-reactivity with other fungi. Furthermore, the test does not distinguish between past and present infection." Histoplasmosis may be associated with other pulmonary diseases, particularly tuberculosis, other fungus diseases, and cancer. The association with pulmonary tuberculosis occurs in 10 to 27 per cent of patients.?" The diagnosis should be considered when chemotherapy for tuberculosis is not followed by the expected response or when other studies indicate its possibility. Chronic pulmonary histoplasmosis more commonly affects the white man above 40 years of age.": 0, 7 The symptoms are varied, the more frequent ones including cough, chest pain, fever, weight loss, fatigue, dyspnea, and hemoptysis. It imitates a variety of diseases, including tuberculosis, other fungus infections, sarcoidosis, and cancer. Of our 155 cases, 153 belong to this group. The two exceptions, who presented with hilar masses, probably should be included in the acute pulmonary disease category, in
The Journal of
166
Saab, Ungaro, Almond
Thoracic ond Cordiovascular Surgery
which surgery is performed for diagnostic purposes. The radiographic appearance in chronic pulmonary histoplasmosis is that of a coin lesion, or histoplasmoma, pulmonary infiltration, cavitation, or mediastinal mass. The lesion may involve part of a lung or the whole lung, and it is often bilateral. The apices are most frequently involved.':" It is progressive in nature, leading to fibrotic and destructive changes in the involved part. Mediastinal fibrosis is another possible sequelae. In untreated cases, the mortality rate is 34 per cent in 4 years, with an additional 23 per cent showing progression in 3 years." To date, experience indicates that the fungostatic drug, amphotericin B, given intravenously, is the drug of choice in the medical therapy of histoplasmosis. Its toxic and side effects are considerable but outweighed by the favorable influence on the course of disseminated and chronic progressive pulmonary histoplasmosis. H The optimum dose is not yet known, but an average course of 2.4 Gm. or 25 to 35 mg. per kilogram of body weight given over 16 weeks was found effective.5, 9 Surgery in chronic pulmonary histoplasmosis. The solitary pulmonary nodule. The lesion may be uncalcified or may contain concentric rings of calcium. It is most commonly caused by histoplasmosis but may be due to a neoplasm or other granulomas. The course is benign, and no treatment is indicated if the lesion is stable over a long period. However, surgery is most often required to establish the diagnosis, and wedge resection is all that is necessary. Amphotericin B therapy or coverage is not indicated, and complications are minimal. a, 4 This experience is confirmed in our series. Mediastinal granulomas. These lesions can cause hemoptysis, broncholiths, atelectasis, bronchiectasis, or endobronchial projections.'- n Surgery may therefore be required. Usually, the contents are evacuated and the wall is partially excised, with the part attached to other structures left intact.
Pulmonary infiltration. Unresolved infiltration is a form of chronic progressive disease and, if untreated, will progress to cavitation." Surgical intervention is indicated for diagnosis and/or resection of localized residual disease or for diagnosis in the diffuse variety. Amphotericin B should be administered when the diagnosis is estabIished.!''
Cavitary histoplasmosis. The purpose of surgery in this type of disease is to remove the residual lesion and focus of infection.v s, 10 This includes cavitation, bronchiectasis, bronchial stenosis with atelectasis, bronchopleural fistula with empyema, destroyed lung, and associated conditions. The favorable results after surgery have been reported by several investigators." 11, 12 In a total of 114 patients treated with surgery alone up until 1969, the over-all mortality rate was 9.6 per cent and the morbidity rate 20 per cent. The mortality rate was reduced to 6 per cent and the morbidity to 13 per cent in 15 patients who received amphotericin B in the preoperative and postoperative periods up to 1969. 7 There is general agreement that amphotericin B in combination with surgery has a favorable effect in reducing the mortality rate and recurrence or progression of the disease in long-term follow-up." u, 10, 13 This is also evident in our series. However, its effect on the incidence of immediate postoperative complications has not been defined. Beatty, Levine," and their colleagues found a decreased incidence of postoperative complications in their patients who had concomitant drug coverage and resection. Furcolow" reported an operative mortality rate of zero in such a group. The only 2 postoperative deaths in our series occurred among patients treated by surgery alone. However, the incidence of postoperative complications in this group was lower than that in patients who received amphotericin B also. The limited experience with thoracoplasty in our series is not encouraging. However, 1 patient who had a destroyed lung and limited pulmonary reserve was treated by thoracoplasty and amphotericin B and is
Volume 68 Number 1
Chronic pulmonary histoplasmosis
167
July, 1974
doing well 3 years after the operation. Hughes and associates" reported good results in a group of 5 patients undergoing plombage thoracoplasty. The procedure could be helpful, in addition to amphotericin B therapy, in patients with severe pulmonary impairment and other associated conditions that significantly increase the risks of pulmonary resection. We wish to express our appreciation for the secretarial assistance of Mrs. Mary Helen Wicks and Miss Rose Spychalski, Missouri State Chest Hospital. REFERENCES
2
3
4
5
Darling, S. T.: A Protozoan General Infection Producing Pseudotubercles in the Lungs and Focal Necroses in the Liver, Spleen, and Lymph Nodes, J. A M. A. 46: 1283, 1906. DeMonbreun, W. A.: The Cultivation and Cultural Characteristics of Darling's Histoplasma capsulatum, Am. J. Trop. Med. 14: 93, 1934. Buechner, H. A: Clinical Aspects of Fungus Diseases of the Lungs Including Laboratory Diagnosis and Treatment, in Banyai, A. L., and Gordon, B. L., editors: Advances in Cardiopulmonary Diseases, vol. III, Chicago, Ill., 1966, Year Book Medical Publishers, Inc., p. 123. Furcolow, M. L., and Buechner, H. A: Histoplasmosis, in Buechner, H. A., editor: Management of Fungus Diseases of the Lungs, Springfield, Ill., 1971, Charles C Thomas, Publisher, chap. 5. Furcolow, M. L.: Comparison of Treated and Untreated Severe Histoplasmosis: A Communicable Disease Center Cooperative My-
coses Study, J. A M. A. 183: 823, 1963. 6 Furcolow, M. L., Doto, I. L., Tosh, F. E., and Lynch, H. J.: Course and Prognosis of Untreated Histoplasmosis: A U. S. Public Health Service Cooperative Mycoses Study, J. A M. A. 177: 292, 1961. 7 Ahn, C., Kilman, J. W., Vasko, J. S., and Andrews, N. C.: The Therapy of Cavitary Pulmonary Histoplasmosis, J. THORAC. CARDIOVASCo SURG. 57: 42, 1969. 8 Veterans Administration-Armed Forces Cooperative Study on Histoplasmosis: Histoplasmosis Cooperative Study II. Chronic Pulmonary Histoplasmosis Treated With and Without Amphotericin B, Am. Rev. Resp. Dis. 89: 641, 1964. 9 Balows, A., editor: Histoplasmosis: Proceedings of the Second National Conference, Springfield, Ill., 1971, Charles C Thomas, Publisher. 10 Sutaria, M. K., Polk, J. W., Reddy, P., and Mohanty, S. K.: Surgical Aspects of Pulmonary Histoplasmosis, Thorax 25: 31, 1970. 11 Polk, J. W., Cubiles, J. A., and Buckingham, W. W.: The Surgical Treatment of Chronic Progressive Pulmonary Histoplasmosis, J. THORAC. SURG. 34: 323, 1957. 12 Dively, W., and McCracken, R.: Cavitary Pulmonary Histoplasmosis Treated by Pulmonary Resection: 13 Year Experience With 29 Cases, Ann. Surg. 163: 921, 1966. 13 Levene, N., Slash, M. Z., Torres, J., and Saliba, N. A: Surgical Aspects of Chronic Progressive Cavitary Pulmonary Histoplasmosis, Ann. Thorac. Surg. 5: 23, 1968. 14 Beatty, O. A, Levene, N., Saliba, A, and Coelho, J.: Surgical Therapy of Chronic Pulmonary Histoplasmosis With and Without Amphotericin B, J. THORAC. CARDIOYASC. SURG. 44: 228, 1962.
Salim B. Saab, M.D., * Ruben Ungaro, M.D., ** and Carl Almond, M.D., *** Columbia and Mt. Vernon, Mo.
HistOPlasma capsulatum was first described and named by Darling ' in 1906, but it was not until 1934 that its identity as a specific fungus was established." Information has been accumulating over the past two decades about the epidemiology, clinical manifestations, natural history, and prognosis of histoplasmosis. Its protean manifestations have been emphasized. The disease has the capacity of involving one organ, usually the lung, or multiple organs. Significant progress has been achieved in the development of diagnostic tests and improved laboratory methods, as well as in treatment of the infection. However, surgical intervention is still required in a good Received for publication March I, 1974. • Assistant Professor of Surgery, University of Missouri Medical Center, Columbia, Missouri, and Associate Chief of Surgery, Missouri State Chest Hospital, Mt. Vernon, Mo. "Resident in Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo., and Missouri State Chest Hospital, Mt. Vernon, Mo . •• • Professor of Surgery and Chief, Section of Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo. 65201.
number of patients for diagnostic and/or therapeutic purposes. The purpose of this paper is to review the experience with 155 patients on whom major thoracic surgical procedures were performed at the Missouri State Chest Hospital in Mt. Vernon, Missouri, over a 20 year period.
Clinical material and methods Between July, 1953, and June, 1973, 155 patients with pulmonary histoplasmosis required thoracic surgical operations at this hospital. The diagnosis was confirmed in all except the only infant in the group by growing the organism in cultures and/or identifying it in tissue specimens. Of the 155 patients, 106 (68 per cent) were male and 49 (32 per cent) were female. Seventy-eight patients (50 per cent) were farmers or had lived on a farm. The age range was 10 months to 75 years, with a peak incidence at 40 to 59 years (49 per cent) (Table I). Symptoms. Twenty-four patients (16 per 159
The Journol of
160
Saab, Ungaro, Almond
Thoracic and Cardiovascular Surgery
Table I. Age Patients Decade
No.
%
~ 9 10-19 20-29 30-39 40-49 50-59 60-69 70-79
2 7 18 24 33 43 24 4 155
1 5 12 15 21 28 15 3 100
Totals
Table II. Symptoms Patients
Asymptomatic Symptomatic Cough Chest pain Fever Weight loss Dyspnea Fatigue Hemoptysis
No.
%
24
16 84 63 43 36 35 33 32 23
131
97 67 55 54 51 49 36
cent) were asymptomatic but were hospitalized because of abnormal findings on chest x-ray examination. The main symptoms in the remaining 131 patients (84 per cent) are listed in Table II. Diagnostic studies. The diagnostic studies are summarized in Table III. Fifty per cent had a positive reaction to the purified protein derivative (P.P.D.), while 78 per cent had a positive histoplasmin skin test. Both tests were positive in 61 patients (40 per cent), whereas in 60 patients (39 per cent) the histoplasmin test was positive but the tuberculin skin test negative. In 15 patients (10 per cent) the histoplasmin skin test was negative and the P.P.D. positive. The complement fixation test was positive in 54 per cent. Both complement fixation and histoplasmin skin tests were positive in 46 per cent and negative in 8 per cent. The skin test was positive but the complement
fixation test negative in 30 per cent, whereas 8 per cent had a negative skin test with a positive complement fixation test. Sputum cultures grew Histoplasma capsulatum in only 48 patients (31 per cent). Forty-five of these had cavitary histoplasmosis and 3 had pulmonary infiltration. None of the patients with coin lesion had a positive sputum culture. The diagnosis was confirmed by histopathological study in 141 patients (91 per cent). Among 78 bronchoscopies performed, 11 yielded some positive information (7 per cent): Evidence of endobronchial disease was discovered in 4 patients, and biopsy revealed squamous cell carcinoma in another 4. The source of bleeding was identified as the right upper lobe in 2, and stenosis of the left upper lobe bronchus was found in I patient. Bronchograms were done on 16 patients. Of these studies, 5 revealed bronchiectasis and 1 showed stenosis of the right middle lobe bronchus. Pulmonary function tests indicated respiratory impairment in 36 patients (23 per cent). In 21 of these the impairment was obstructive in nature, in 6 it was restrictive, and in 9 it was mixed. Table IV summarizes the radiologic appearance and lobar involvement. Thirtyeight patients (25 per cent) had a solitary, unilateral pulmonary nodule (coin lesion). The lesion showed as a pulmonary infiltrate in 23 patients (15 per cent), bilateral in 7. Ninety-two patients (59 per cent) had a cavitary lesion, unilateral in 65, and bilateral in 27. Two patients presented with a right hilar mass. Except in patients with coin lesion, the upper lobes were most frequently involved. The right upper lobe was involved in 87 patients and the left upper lobe in 69. Associated diseases. Sixty-seven patients (43 per cent) had one or more diseases in addition to pulmonary histoplasmosis (Table V). Pulmonary tuberculosis was present in 22 patients (14 per cent), emphy-
Volume 68
Chronic pulmonary histoplasmosis
Number 1
16 1
July. 1974
Table III. Diagnostic tests Positive Test
P.P.D. Histoplasmin skin test Complement fixation Sputum culture Histopathology Bronchoscopy Bronchogram Pulmonary function tests
Negative
Not done
No.
%
No.
%
No.
77
50 78 54 31 91 7 4 23
77
50 19 37 69 8 43 6 66
1 4 14
121 84 48 141 II
6 36
30 57 107 13 67 IO
102
I I 77
139 17
%
3 9 1 I
50 90 I1
Legend: P.P.D., Purified protein derivative.
Table IV. Radiographic localization by type of lesion Type oj lesion
Coin lesion
Unilateral Bilateral RUL RML RLL LUL LLL Totals
38 0 7 0 7 9 15 38
Cavitary disease
Pulmonary infiltrate
Right hilar mass
65 27 68 17
16 7 12 4 6
2 0
13
49 7 92
II
5 23
2
Totals
121 34 87 21 26 69 27 155
Legend: RUL, Right upper lobe. RML, Right middle lobe. RLL, Right lower lobe. LUL, Left upper lobe. LLL, Left lower lobe.
serna in 15, and bronchogenic carcinoma in II patients. Results A total of 174 thoracic surgical procedures were performed on 155 patients. The 19 reoperations were done on 18 patients. In 5 of these the indication was recurrence or progression of the disease, and in 13 it was to treat complications: Six thoracoplasties were done to obliterate an apical space, and 6 were for postresection bronchopleural fistula. One patient required pleurectomy for empyema. Eight patients were lost to follow-up but were in improved condition at the time of discharge, The remaining 147 patients were followed for 2 months to 13 years, with an average of 48 months. Among 20 late deaths, the cause of death was not known in 2. Only 5 patients died because of progression of the disease, whereas 8 patients died
of bronchogenic carcinoma. The cause of death was pneumonia in 2, emphysema in 1, pulmonary embolism in 1, and acute monocytic leukemia in 1. Twenty-eight patients (18 per cent) developed complications in the immediate postoperative period. Tables VI to IX summarize the indications for surgery, the primary thoracic operations, the postoperative complications, and the long-term results in the entire group. Coin lesions. Thirty-eight patients belonged to this category. Wedge resection was done in 34, lobectomy in 3, and pneumonectomy in 1. The indication for surgery was to obtain a definite diagnosis and rule out neoplasm in 35, Of these, 1 patient had a Class IV sputum cytology, with a 2.5 em. nodule in the right lower lobe, but pathological study of the excised nodule showed no cancer. The patient is doing well 2 years postoperatively, Lobectomy in another pa-
1 62
The Journal of Thoracic and Cardiovascular
Saab, Ungaro, Almond
Surgery
Table VI. Indications for surgery
Table V. Associated diseases Type of disease
No.
Pulmonary tuberculosis Pulmonary emphysema Bronchogenic carcinoma Cardiac disease Aspergillosis Diabetes mellitus Peptic ulcer Liver cirrhosis Chronic brain syndrome Hypertension Cholelithiasis Pneumothorax with cystic lung disease Bronchial asthma Interstitial pneumonitis Malignant lymphoma Fibrosarcoma of chest wall Herniated cervical disc Total
22 15 11 5 4 4 2 2 2 2 2 1 1 I I 1 I 77
tient revealed carcinoma in situ of the left upper lobe in addition to the histoplasmoma. He is doing well 1 year after operation. Of the remaining 3 patients, 1 required a pneumonectomy for squamous cell carcinoma of the left main-stem bronchus diagnosed by bronchoscopy and associated with a histoplasmoma. The patient is free of recurrence 2 years after operation. The second patient had a Histoplasma granuloma in the left lower lobe, with spontaneous pneumothorax secondary to cystic disease in the left upper lobe. Wedge resection of the nodule was performed, with excision of the cystic lesion. The third patient presented with left pleural effusion and a coin lesion in the left lower lobe. Pleural biopsy was not diagnostic, and two histoplasmomas were resected from the left upper and lower lobes at thoracotomy. The patient died 10 months later due to acute monocytic leukemia and cerebrovascular accident. This patient, plus 1 patient who died of pulmonary emphysema 9 years after wedge resection of a histoplasmoma, were the only ones in this group to die late after operation. Immediate postoperative complications included atelectasis, which responded to bronchoscopy and suctioning in 1 patient, and wound dehiscence, which was treated
Indication Coin lesion Pulmonary infiltration Unresolved Associated bronchiectasis Right middle lobe syndrome Associated cystic disease Persistent pleural effusion Diagnostic biopsy Associated carcinoma Associated tuberculosis Cavitary disease Resection of cavitary disease Destroyed lung Bronchiectasis Bronchopleural fistula Bronchial stenosis Associated carcinoma Associated tuberculosis Severe hemoptysis Right hilar mass (diagnostic)
No. 38 23 11 I I I I 3 3 2 92 61 7 5 3 I 6 7 2 2
by secondary closure in the only patient who had a pneumonectomy. None of the patients with coin lesion received amphotericin B, and none showed evidence of recurrence or progression of the disease. There were no late deaths related to histoplasmosis in this group. Pulmonary infiltration. This group included 23 patients. Lobectomy was done in 8, and wedge resection, segmental resection, and lung biopsy in 4 each. Two patients underwent pneumonectomy for associated bronchogenic carcinoma, and 1 patient required pleurectomy for persistent pleural effusion. An associated unresectable bronchogenic carcinoma was present in 1 patient who had lung biopsy. Eleven patients required surgery for unresolved pulmonary infiltrates and 2 for associated pulmonary tuberculosis. Bronchiectasis, right middle lobe syndrome, and cystic lung disease led to surgery in 1 patient each. Surgery was the only treatment in 15 patients. Postoperative complications occurred in 4 of these (27 per cent), and the disease progressed in 2 ( 13 per cent) . Eight patients had surgery plus amphoteri-
Volume 68
Chronic pulmonary histoplasmosis
Number 1
163
July, 1974
Table VII. Primary pulmonary operations Cavitary disease
Pulmonary infiltrate
Type of operation
Coin lesion
Wedge resection Segmental resection Lobectomy Lobectomy and wedge Pneumonectomy Thoracoplasty Lung biopsy Pleurectomy Hilar lymph node biopsy
34
1
4
0
0 3
19
4
0
48 10 9 4
7 1 2 0
I
4 I 0
0 0 0 0 0 0
0 1 0 0 0 0
0 0
Hilar mass
2
Table VIII. Immediate postoperative complications No.
Treatment
Persistent air space
Type of complication
6
Bronchopleural fistula Atelectasis
5
Pneumoperitoneum (2) Thoracoplasty (4) Thoracoplasty Bronchoscopy (4) Tracheostomy (1) Secondary closure Deroofing of space and antituberculosis therapy Anticoagulation Digitalis and diuretics Pleurectomy Tube drainage Conservative Conservative
Wound infection Loculated fluid with Mycobacterium tuberculosis Thrombophlebitis Pulmonary edema Empyema Pleural effusion Pericarditis Serum hepatitis
cin B. The latter was started preoperatively when the diagnosis was known and postoperatively when the diagnosis was established later. Only 1 patient (12 per cent) had a postoperative complication, and none had progression of the disease. There were no operative or late deaths due to histoplasmosis in patients with pulmonary infiltration. Hilar mass. Chest x-ray films in 2 patients showed a right hilar mass. These 2 patients were a 10-month-old girl, the youngest patient in the series, and a 16-year-old boy. In both, the P.P.D. skin tests and cultures for Histoplasma capsulatum and acid-fast bacilli were negative, but the histoplasmin skin tests and complement fixation tests were positive. Thoracotomy was recommended to confirm the suspected diagnosis. In the infant, biopsy of enlarged hilar lymph nodes showed a caseating granuloma. The
6 4
patient was given 60 mg. of amphotericin B postoperatively, although Histoplasma capsulatum was not identified by histopathology. The x-ray appearance and febrile course improved over 6 months of followup. In the second patient, pathological study of the hilar lymph node biopsy confirmed the diagnosis of histoplasmosis, and he was given a full course of amphotericin B postoperatively. He is doing well 3 years after the operation. Cavitary disease. Ninety-two patients, the largest number in this series, had chronic cavitary histoplasmosis. Fifty-eight patients had a lobectomy or lobectomy plus wedge resection, 19 patients had segmental resection, 9 required a pneumonectomy, and 1 had a wedge resection. Thoracoplasty was done in 4 patients-for bronchopleural fistula in 3 and for a destroyed lung in a patient with mixed impairment of pulmonary
The Journal of
164
Saab, Ungaro, Almond
Thoracic and Cardiovascular Surgery
Table IX. Total results over the follow-up period Type of lesion Coin lesion Surgery Surgery + ampho. B Infiltrate Surgery Surgery + ampho. B Cavitary disease Surgery Surgery + ampho. B Hilar mass Surgery Surgery + ampho. B Totals
I
IProgression
Postoperative complications
Operative deaths
0
2 0
0 0
0 0
0 0
15 8
4 1
0 0
0 0
0
44 48
7 14
2
3 2
11
0
0
0 0
0 0
0 0
0 0
28
2
5
17
Late deaths due to Histo.
No.
38
2 155
Late deaths due to Histu.
disease
of
2
4
Table X. Results in patients with cavitary histoplasmosis Mode of treatment Surgery + adequate ampho. B preop. Surgery + adequate ampho. B postop. Surgery + adequate ampho. B pre. and postop. Totals Surgery only Surgery + incomplete ampho. B
IProgression
No.
Postoperative complications
Operative deaths
12
5
o
9
3
o
18
4
o
39 44 9
12 7 2
o
1
2
2
3
11
1
2
function. Lung biopsy was done in 1 patient only, who was found to have an associated unresectable carcinoma. The most frequent indication for surgery in this group was resection of chronic cavitary histoplasmosis in 61 patients. Other indications included destroyed lung in 7, associated tuberculosis in 7, associated carcinoma in 6, bronchiectasis in 5, bronchopleural fistula in 3, severe hemoptysis in 2, and bronchial stenosis in 1 patient. Pneumonectomy was performed in 6 patients with destroyed lung and 3 patients with associated bronchogenic carcinoma. Of the 3 patients with bronchopleural fistula and empyema treated by thoracoplasty, 1 patient was lost to follow-up and the other 2 died 6 months and 3 years after operation due to progression of the disease.
o
I
disease
o
o
o
o
of
2
In 45 patients, the diagnosis was known preoperatively by positive sputum cultures. In 26 patients, the diagnosis was suspected because of the x-ray appearance with positive complement fixation tests and/or positive histoplasmin skin test and negative P.P.D. test. It was confirmed postoperatively by pathological study. The diagnosis was made postoperatively only, by positive pathological examination, in the remaining 21 patients. Forty-four patients had surgery only (Group A). Seven of these (16 per cent) developed complications and 2 died (4.4 per cent) in the postoperative period. There were 3 late deaths due to histoplasmosis (7 per cent), and 11 patients (25 per cent) exhibited progression of disease. The other 48 patients were treated by operation and
Volume 68 Number 1 July, 1974
administration of amphotericin B (Group B). Postoperative complications occurred in 14 (29 per cent), but there were no operative deaths. There were 2 late deaths due to histoplasmosis (4 per cent). Progression of the disease was documented in 4 patients (8 per cent). Further analysis of the results of surgery in patients with cavitary histoplasmosis in relation to amphotericin B therapy is shown in Table X. Nine patients in Group B did not receive the complete course of amphotericin B that is considered adequate. Adequate dosage is defined as 35 mg. per kilogram of body weight, or a total of around 2 Gm., administered intravenously over a period of around 16 weeks. Of the remaining 39 patients who had adequate amphotericin B therapy in the preoperative, postoperative, or both periods, 12 patients (3 I per cent) developed postoperative complications, with no operative deaths. The disease process progressed in 2 patients (5 per cent), and there was 1 late death due to histoplasmosis (2.5 per cent). Discussion It is estimated that half a million new Histoplasma capsulatum infections occur annually in the United States." Although the clinical manifestations of the disease cover a wide spectrum, three principal types have been recognized- 4: 1. The acute pulmonary form, which is an influenza-like illness, usually is selflimited but can progress to pneumonitis or form a primary complex simulating the Gohn complex of tuberculosis. It usually requires no treatment except in the occasional severe case with protracted course. 2. Disseminated histoplasmosis, acute or chronic, indicates hematogenous extrapulmonary spread and may resemble miliary tuberculosis. It may be fulminating in nature or may progress slowly over a period of years. Urgent medical treatment is required to prevent a usually fatal outcome." 3. Chronic pulmonary histoplasmosis may be the result of reactivation or progression of the primary infection or may represent
Chronic pulmonary histoplasmosis
165
an exogenous reinfection. It is the form most commonly encountered in practice and interests the thoracic surgeon because it requires medical and surgical treatment. A definite diagnosis of histoplasmosis is established only if the fungus is grown in cultures, usually of sputum or tissue specimen, or if it is identified in tissues by differential staining, usually with methenamine silver. Experience at the Missouri State Chest Hospital indicates that isolation of the organism is more successful in patients with chronic cavitary disease than in those with other types. Multiple specimens have to be processed, and animal inoculation should be resorted to at times. Sputum cultures give the best yield, whereas bronchial and gastric washings provide the poorest yield. The histoplasmin skin test determines delayed hypersensitivity to histoplasmosis, which is usually demonstrated in 2 weeks after exposure. Its use lies in defining endemic areas, but its value as a diagnostic tool is limited in several ways: False-positive and false-negative results do occur, as does cross-reactivity with other fungi. Furthermore, the test does not distinguish between past and present infection." Histoplasmosis may be associated with other pulmonary diseases, particularly tuberculosis, other fungus diseases, and cancer. The association with pulmonary tuberculosis occurs in 10 to 27 per cent of patients.?" The diagnosis should be considered when chemotherapy for tuberculosis is not followed by the expected response or when other studies indicate its possibility. Chronic pulmonary histoplasmosis more commonly affects the white man above 40 years of age.": 0, 7 The symptoms are varied, the more frequent ones including cough, chest pain, fever, weight loss, fatigue, dyspnea, and hemoptysis. It imitates a variety of diseases, including tuberculosis, other fungus infections, sarcoidosis, and cancer. Of our 155 cases, 153 belong to this group. The two exceptions, who presented with hilar masses, probably should be included in the acute pulmonary disease category, in
The Journal of
166
Saab, Ungaro, Almond
Thoracic ond Cordiovascular Surgery
which surgery is performed for diagnostic purposes. The radiographic appearance in chronic pulmonary histoplasmosis is that of a coin lesion, or histoplasmoma, pulmonary infiltration, cavitation, or mediastinal mass. The lesion may involve part of a lung or the whole lung, and it is often bilateral. The apices are most frequently involved.':" It is progressive in nature, leading to fibrotic and destructive changes in the involved part. Mediastinal fibrosis is another possible sequelae. In untreated cases, the mortality rate is 34 per cent in 4 years, with an additional 23 per cent showing progression in 3 years." To date, experience indicates that the fungostatic drug, amphotericin B, given intravenously, is the drug of choice in the medical therapy of histoplasmosis. Its toxic and side effects are considerable but outweighed by the favorable influence on the course of disseminated and chronic progressive pulmonary histoplasmosis. H The optimum dose is not yet known, but an average course of 2.4 Gm. or 25 to 35 mg. per kilogram of body weight given over 16 weeks was found effective.5, 9 Surgery in chronic pulmonary histoplasmosis. The solitary pulmonary nodule. The lesion may be uncalcified or may contain concentric rings of calcium. It is most commonly caused by histoplasmosis but may be due to a neoplasm or other granulomas. The course is benign, and no treatment is indicated if the lesion is stable over a long period. However, surgery is most often required to establish the diagnosis, and wedge resection is all that is necessary. Amphotericin B therapy or coverage is not indicated, and complications are minimal. a, 4 This experience is confirmed in our series. Mediastinal granulomas. These lesions can cause hemoptysis, broncholiths, atelectasis, bronchiectasis, or endobronchial projections.'- n Surgery may therefore be required. Usually, the contents are evacuated and the wall is partially excised, with the part attached to other structures left intact.
Pulmonary infiltration. Unresolved infiltration is a form of chronic progressive disease and, if untreated, will progress to cavitation." Surgical intervention is indicated for diagnosis and/or resection of localized residual disease or for diagnosis in the diffuse variety. Amphotericin B should be administered when the diagnosis is estabIished.!''
Cavitary histoplasmosis. The purpose of surgery in this type of disease is to remove the residual lesion and focus of infection.v s, 10 This includes cavitation, bronchiectasis, bronchial stenosis with atelectasis, bronchopleural fistula with empyema, destroyed lung, and associated conditions. The favorable results after surgery have been reported by several investigators." 11, 12 In a total of 114 patients treated with surgery alone up until 1969, the over-all mortality rate was 9.6 per cent and the morbidity rate 20 per cent. The mortality rate was reduced to 6 per cent and the morbidity to 13 per cent in 15 patients who received amphotericin B in the preoperative and postoperative periods up to 1969. 7 There is general agreement that amphotericin B in combination with surgery has a favorable effect in reducing the mortality rate and recurrence or progression of the disease in long-term follow-up." u, 10, 13 This is also evident in our series. However, its effect on the incidence of immediate postoperative complications has not been defined. Beatty, Levine," and their colleagues found a decreased incidence of postoperative complications in their patients who had concomitant drug coverage and resection. Furcolow" reported an operative mortality rate of zero in such a group. The only 2 postoperative deaths in our series occurred among patients treated by surgery alone. However, the incidence of postoperative complications in this group was lower than that in patients who received amphotericin B also. The limited experience with thoracoplasty in our series is not encouraging. However, 1 patient who had a destroyed lung and limited pulmonary reserve was treated by thoracoplasty and amphotericin B and is
Volume 68 Number 1
Chronic pulmonary histoplasmosis
167
July, 1974
doing well 3 years after the operation. Hughes and associates" reported good results in a group of 5 patients undergoing plombage thoracoplasty. The procedure could be helpful, in addition to amphotericin B therapy, in patients with severe pulmonary impairment and other associated conditions that significantly increase the risks of pulmonary resection. We wish to express our appreciation for the secretarial assistance of Mrs. Mary Helen Wicks and Miss Rose Spychalski, Missouri State Chest Hospital. REFERENCES
2
3
4
5
Darling, S. T.: A Protozoan General Infection Producing Pseudotubercles in the Lungs and Focal Necroses in the Liver, Spleen, and Lymph Nodes, J. A M. A. 46: 1283, 1906. DeMonbreun, W. A.: The Cultivation and Cultural Characteristics of Darling's Histoplasma capsulatum, Am. J. Trop. Med. 14: 93, 1934. Buechner, H. A: Clinical Aspects of Fungus Diseases of the Lungs Including Laboratory Diagnosis and Treatment, in Banyai, A. L., and Gordon, B. L., editors: Advances in Cardiopulmonary Diseases, vol. III, Chicago, Ill., 1966, Year Book Medical Publishers, Inc., p. 123. Furcolow, M. L., and Buechner, H. A: Histoplasmosis, in Buechner, H. A., editor: Management of Fungus Diseases of the Lungs, Springfield, Ill., 1971, Charles C Thomas, Publisher, chap. 5. Furcolow, M. L.: Comparison of Treated and Untreated Severe Histoplasmosis: A Communicable Disease Center Cooperative My-
coses Study, J. A M. A. 183: 823, 1963. 6 Furcolow, M. L., Doto, I. L., Tosh, F. E., and Lynch, H. J.: Course and Prognosis of Untreated Histoplasmosis: A U. S. Public Health Service Cooperative Mycoses Study, J. A M. A. 177: 292, 1961. 7 Ahn, C., Kilman, J. W., Vasko, J. S., and Andrews, N. C.: The Therapy of Cavitary Pulmonary Histoplasmosis, J. THORAC. CARDIOVASCo SURG. 57: 42, 1969. 8 Veterans Administration-Armed Forces Cooperative Study on Histoplasmosis: Histoplasmosis Cooperative Study II. Chronic Pulmonary Histoplasmosis Treated With and Without Amphotericin B, Am. Rev. Resp. Dis. 89: 641, 1964. 9 Balows, A., editor: Histoplasmosis: Proceedings of the Second National Conference, Springfield, Ill., 1971, Charles C Thomas, Publisher. 10 Sutaria, M. K., Polk, J. W., Reddy, P., and Mohanty, S. K.: Surgical Aspects of Pulmonary Histoplasmosis, Thorax 25: 31, 1970. 11 Polk, J. W., Cubiles, J. A., and Buckingham, W. W.: The Surgical Treatment of Chronic Progressive Pulmonary Histoplasmosis, J. THORAC. SURG. 34: 323, 1957. 12 Dively, W., and McCracken, R.: Cavitary Pulmonary Histoplasmosis Treated by Pulmonary Resection: 13 Year Experience With 29 Cases, Ann. Surg. 163: 921, 1966. 13 Levene, N., Slash, M. Z., Torres, J., and Saliba, N. A: Surgical Aspects of Chronic Progressive Cavitary Pulmonary Histoplasmosis, Ann. Thorac. Surg. 5: 23, 1968. 14 Beatty, O. A, Levene, N., Saliba, A, and Coelho, J.: Surgical Therapy of Chronic Pulmonary Histoplasmosis With and Without Amphotericin B, J. THORAC. CARDIOYASC. SURG. 44: 228, 1962.