356

latently infected birds. Coupled with evidence that psittacosis has long-term effectslg and is a communicable disease of humans, our findings prompt tighter restrictions on the import of psittacines and suggest that psittacosis should be made a notifiable disease. We thank Dr G. A. Cullen (Central Veterinary Laboratory, Weybridge) for the examination of pathological specimens and Dr P. Keith for the epidemiological information.

Requests for reprints should be addressed to J.W.

REFERENCES K. F. Archs environ. Hlth, 1969, 19, 461. Olson, B. J., Treuting, W. L. Publ. Hlth Rep. (Wash), 1944, 59, 1299. Schacter, J. in Disease Transmitted from Animals to Man (edited by W. T. Hubbert); Springfield, Illinois, 1975. 4. Meyer, K. F. in Viral and Rickettsial Infection in Man (edited by F. L. Horsfall and I. Tamm), London,1965. 5. Br. med. J. 1972, i, 1. 6. Fraser. D. W. and others New Engl. J. Med. 1977, 297, 1189. 7. Bevan, B. J., Cullen, G. A., Read, W. M. F. Avian Path. 1978, 7, 203. 8. Horden, T., Gow, A. E. Lancet, 1930, i, 442. 9. Grist, N. R., McLean, C. Br. med. J. 1964, ii, 21. 10. Meyer, K. F., Eddie, B. Am. Rev. tuber. pulmon. Dis. 1956, 74, 566. 11. Yow, E. M., Brennan, J. C., Preston, J., Levy, S. Am. J. Med. 1959, 27, 739. 12. Fisher, H. R., Helsby, R. J. Br. med. J. 1931, i, 887. 13. Polayes, S. H., Lederer, M. Archs intern. Med. 1932, 49, 253. 14. Levison, D. A., Guthrie, W., Ward, C., Green, D. M., Robertson, P. G. C. Lancet, 1971, ii, 844. 15. Carr-Locke, D. L., Mair, H. J. Br. med J. 1976, ii, 853. 16. Dymock, J. W. Br. J. clin. Pract, 1971, 25, 5, 240. 17. Coil, R., Horner, I. Br. med. J. 1967, iv, 35. 18. Ward, C., Ward, A. M. Lancet, 1974, ii, 734. 19. Lancet, 1973, ii, 1246.

1. 2. 3.

Meyer,

First Case A dental nurse aged 19 complained of right-sided chest and back pain associated with tachycardia and wheeling bu - H( pyrexia. Her general practitioner prescribed broiichodilatorc and antibiotics. The chest pain subsided, but because of increasmg shortness of breath she was referred to hospital mr. days after the onset of symptoms, She was brèalt1Ì;;;sf and slightly cyanosed, and there were signs of G righi-siclea pi’tcumothorax, confirmed radiologically. During insertion of a right-sided chest drain with underwater seal she began to cough intensely, but the cough and breathlessness settled over the next hour. Then the cough returned with increasing amounts of white frothy sputum. A further dh-es- X-ray ng. 1 showed complete re-expansion with mulupie f1C·CSLtIdC shadows throughout the right lung field. She became iricreasingly dyspnodc and had a respiratory and cardiac a; re" After. routine resuscitative measures there was a sinjs tachyardia

lung

TWO UNEXPECTED DEATHS FROM PNEUMOTHORAX R. C. PEATFIELD N. McI.

P. R. EDWARDS

JOHNSON

Cardiothoracic Department, Central Middlesex Hospital, London NW10

patients with primary spontaneous pneumothorax died despite intensive treatment. In the first the pneumothorax had been present for 10 days, and, after insertion of a chest drain, pulmonary œdema developed unilaterally, followed by cardiac arrest. She was resuscitated, but later died of a tension pneumothorax on the other side, probably due to Two

Summary

Fig. I-Chest X-ray in case 1 showing full of fight lun!5’ with multiple fioccular opacities.

cardiac massage and artificial ventilation. In the second patient, after insertion of a chest drain, mediastinal emphysema spread to the head and neck, causing fatal obstruction of the hypopharynx. Introduction

pneumothorax is usually caused by spontaneous rupture of an apical lung bulla. Death is uncommon : Killen and Gobbet found only 57 deaths in 3347 published cases (1.7%). Most of these fatal cases IN adults

were

associated with serious conditions such

losis, chest

trauma,

bronchitis,

or

lung

as

tubercu-

tumour.

In

un-

the death-rate was only 0-9%, and these deaths were usually due to tension pneumothorax, hxmothorax, or bilateral simultaneous pneumothorax.2-4 We report here two cases of primary spontaneous pneumothorax which ended fatally through different complications.

complicated

cases

Fig. 2-Chest X-ray in same patient, nom showing more apsq:: right lung and a left-sided tension pneumothura.

357 and she eBer. mm so

was

breathing spontaneously. Breathing

was, how-

inadequate (arterial-blood pH 7.16, 1’oz 17.2 kPa [129 Hg], PCo2, 9.2 kPa [69 mm Hg], bicarbonate 24 mmol/1)

she

was

ventilated. She tolerated this well for about half an

hour, after which bradycardia developed and she had asystolic A chest X-ray at that time showed a tension the left (fig.2). Despite insertion of a drain on that side she could not be resuscitated. At necropsy bilateral cystic emphysematous bulls were found at the apices. The lungs were partly collapsed with some basal consolidation. There was evidence of considerable cerebral anoxia.

cardiac

arrest.

pneumothorax

on

Second Case A telephone engineer aged 58 was admitted as an emergency with right-sided pleuritic pain that had started the previous day. He was very short of breath and there were signs of a

right-sided pneumothorax, confirmed by chest X-ray which also revealed a pleural adhesion to the lateral wall of the right hemithorax (fig. 3). A chest drain was inserted with underwater seal and repeat chest X-ray showed satisfactory re-expansion. 48 hours after admission his neck began to swell and he complained of difficulty in swallowing. There was surgical emphysema of the neck, chest, shoulders, and back; both lungs were fully expanded but on the chest X-ray the aortic knuckle was outlined by air (fig. 4), indicating mediastinal emphysema. The entry site of the drain was resutured but the surgical emphysema continued to increase. Low-pressure suction was applied to the drain, to produce continuous bubbling of air, but the surgical emphysema progressed and soon prevented the patient from opening his eyes or mouth. Chest X-ray showed a persistent small right pneumothorax with greatly increased surgical emphysema. 24 hours after the onset of surgical emphysema he had a respiratory arrest, and intubation proved impossible because of soft-tissue swelling in the hypopharynx. By the time emergency tracheostomy was done he had a profound bradycardia which progressed to asystole. Resuscitative measures, including drainage of the left hemithorax, proved unsuccessful. Necropsy revealed severe bilateral lung emphysema with a large apical bulla.

Discussion

Fig. 3-chest X-ray in case 2 on admission, showing complete right pneumothorax and small pleural adhesion.

Fig 4-Chest X-ray two days later, and extensive surgical emphysema.

showing

full

re-expansion

In the first patient death was due to the contralateral tension pneumothorax, and this in turn was probably produced by the initial resuscitation-in particular, external cardiac massage and ventilation. Pneumothorax is notoriously hard to recognise in patients on ventilators. A contralateral prophylactic chest drain might have prevented her death, but would not have been without risk. Pulmonary oedema has been reported in only 19 cases of pneumothorax, though it isawellknown complication when pleural effusions are drained rapidly.6.7 In all but 1 of the 19 cases2,6-11 the pneumothorax had been present for at least three days, and in 9 cases suction had been applied to aid re-expansion. In animals pulmonary oedema cannot be produced unless the pneumothorax has been present for three days and suction is applied.12 Possible mechanisms include anoxia of the capillary endothelium leading to increased permeability,7,12 increased capillary leakage due to suction drainage,’, 12-16 and loss of surfactant in collapsed lungs.6,17 Of the 19 patients with pulmonary oedema after treatment of pneumothorax, 5 died and 2 required mechanical ventilation before recovery. Surgical emphysema is very common but rarely fatal. In cases associated with pneumothorax death has been attributed to three possible mechanisms---compression of the heart and great vessels by air, compression of the airway in the hypopharynx, and tension in the pneumothorax. We believe that the second mechanism was responsible for the death of our second patient. Mediastinal compression is thought to be reduced by escape of air into the subcutaneous tissues of the neck,’s·’9 as happened here; endotracheal intubation was impossible because of the soft tissue swelling in the neck; and the agonal sinus bradycardia was more suggestive of anoxia than of circulatory obstruction. Because most patients do well with conservative measures, there has been little discussion of the treatment of mediastinal emphysema. Extraction of air from the hemithorax may prevent air escape into the mediastinum, but this proved ineffective in our patient; we

358 believe that his pleural adhesion held the tear in the visceral pleura open, allowing a continuous leak with subpleural tracking. Macklin and Macklin’9 suggested that pleural adhesions which prevent part of the lung from collapsing may lead to local hyperexpansion, enabling the escape of air into the lung interstices (pulmonary interstital emphysema) and thence via the hilum into the mediastinum. After our experience in these two fatal cases we suggest that any pneumothorax of more than 72 hours’ duration should be drained slowly. If the patient begins to cough, possibly indicating the onset of pulmonary oedema, the tube should be clamped at once. If artificial ventilation proves necessary, great care should be taken in looking for a contralateral pneumothorax, and a prophylactic chest drain on the unaffected side should be considered. If a pleural adhesion prevents complete collapse in patients with continuing surgical emphysema, there may be a case for its division at thoracoscopy or for closure of the lung tear at thoracotomy. In a patient whose airway is endangered by mediastinal and severe

cervical emphysema, tracheostomy will ensure airway and release some of the interstitial air.20

We thank Dr M. W. McNicol and Dr J. F. Riordan for permission report on their patients, and Mrs B. Frost and Mrs P. Jennings for the typing.

to

REFERENCES 1. Kjaergaard, H. Acta med. scand. 1932, suppl. 43. 2. Killen, D. A., Gobbel, W. G. Spontaneous Pneumothorax. Boston, 1968. 3. Geisler, L. S., Savic, B. Prax. Pneumol. 1976, 30, 73. 4. Mills, M., Baisch, B. F. Ann. thorac, Surg. 1965, 1, 286. 5. Estafanous, F. G., et al. Anæsth. Analg. 1975, 54, 730. 6. Trapnell, D. H., Thurston, J. G. B. Lancet, 1970, i, 1367. 7. Carlson, R. I., et al. Surg. Forum, 1959, 9, 367. 8. Grant, M. J. A. New Z. med. J. 1971, 74, 250 9. Schwander, D., et al. Helv. chir. Acta, 1973, 40, 393. 10. Shanahan, M. X., et al. Anæsth. intens. Care, 1975, 3, 19. 11. Waqaruddin, M., Bernstein, A. Thorax, 1975, 30, 54. 12. Miller, W. C., et al. Am. Rev. resp. Dis. 1973, 108, 664. 13. Sautter, R. D., et al. Chest, 1971, 60, 399. 14. Humphreys, R. L., Berne, A. S. Radiology, 1970, 96, 509. 15. Childress, M. E., et al. Am. Rev. resp. Dis. 1971, 104, 119. 16. Ziskind, M. M., et al. ibid. 1965, 92, 632. 17. Ratliff, J. L., et al. Chest, 1973, 64, 654. 18. Millard, C. E. Postgrad. Med. 1971, 49, 117. 19. Macklin, M. T., Macklin, C. C. Medicine, Baltimore, 1944, 23, 281. 20. Rydell, J. R., Jennings, W. K. Archs Surg. 1955, 70, 647.

Preliminary Communications

larger 8 radiation

fields have not improved the curerate.7 Extensive disease (stage III or iv) has generally been treated with systemic chemotherapy. DeVita and his associates demonstrated that combination chemotherapy was curative in 30-40% of patients with advanced disease.9 Newer drug regimens containing doxorubicin (’Adriamycin’) appear to have further improved the results achieved with chemotherapy. 10 " This report summarises our experience with adriamy-

CHEMOTHERAPY OF LOCALISED HISTIOCYTIC LYMPHOMA THOMAS P. MILLER

STEPHEN E. JONES

Section of Hematology and Oncology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, U.S.A.

Summary

22

patients

with localised

(stage

an

I or

cin-containing combination chemotherapy rather than radiotherapy as primary treatment for localised diffuse lymphoma.

II)

diffuse lymphoma were treated with chemotherapy at the time of diagnosis. 14 patients received chemotherapy as the only treatment, and 8 received chemotherapy plus local irradiation. Doxorubicin-containing drug regimens were used in 20 patients. All 22 patients achieved a complete remission and remain alive with a median survival from the time of diagnosis of 27+ months. 21 patients (95%) have remained continuously free of disease with a median disease-free survival from the completion of chemotherapy of 23+ months. These findings provide a strong rationale for further clinical trials of chemotherapy alone or chemotherapy followed by regional radiotherapy for localised stages of diffuse lymphoma.

PATIENTS AND METHODS

Between November, 1971, and December, 1978, 22 patients treated for localised non-Hodgkin’s lymphoma. The orig-

were

inal

biopsy material, classified according to the scheme of Rappaport,12 showed the following histological distribution: 18 patients had diffuse histiocytic lymphoma, 2 patients had mixed histiocytic-lymphocytic lymphoma, and 2 patients had minimally nodular histiocytic lymphoma (the latter entity has a prognosis similar to D. H.L. 11). All patients were carefully staged by lymphangiography and bone-marrow core biopsy.i4’j8 peatients also underwent exploratory laparotomy.16 The extent of disease- was classified according to the criteria of the Ann

INTRODUCTION

histiocytic lymphoma (D.H.L.) is a highly malignant lymphoma characterised by rapid growth, a propensity for early dissemination through the bloodstream, and rapid recurrence after inadequate or unsuccessful treatment.I-3 Historically, the choice of treatment has been determined by the extent of disease at diagnosis. The more localised forms of the disease-i.e., lymphoma confined to one side of the diaphragm (stage I or 11)—have been treated with radiotherapy. Radiation therapy has proved curative in 45-65% of patients with very localised disease (stage 1).4-6 However, radiotherapy has been considerably less successful in patients with stage-II disease,.34 Higher dosages of radiation and DIFFUSE

.,

Arbor conference. 17 All patients received intensive intermittent combination chemotherapy. 14 patients received chemotherapy as the only therapy, and 8 patients were treated with both chemotherapy and radiation. 19 patients received the four-drug regimen, CHOP, which combines cyclophosphamide, adriamycin, vincristine, and prednisone in a schedule which is repeated every 21 days." 1 patient received HOP (adriamycin, vincristine, and prednisone) every 21 days.10 2 patients with heart-disease received combination chemotherapy without adriamycin.9 Patients treated with chemotherapy alone received between six and eleven courses of CHOP (average eight). Patients receiving both chemotherapy and radiotherapy were given involvedfield radiation with a minimum dosage of 4500 rad (range 4500-6000 rad). 5 patients received chemotherapy with two courses of CHOP before radiation therapy. Thus, 19 of 22 patients received chemotherapy as their first form of therapy. The remaining 3 patients began chemotherapy at the same