Eur J Cardiothorac Surg 2001;20:1113-1116
© 2001 Elsevier Science NL
Bilateral bronchioloalveolar lung carcinoma: is there a place for palliative pneumonectomy?
Fabrice Barlesia,
Christophe Doddolib,
Pascal Thomasb,c,
Jean-Pierre Kleisbauera,
Roger Giudicellib,
Pierre Fuentesb
a Department of Thoracic Oncology, Sainte-Marguerite Hospital, Marseille, France
b Department of Thoracic Surgery, Sainte-Marguerite Hospital, Marseille, France
c UPRES, EA 2201, Laboratoire de physiopathologie respiratoire, Faculté de médicine Nord, 35 Bd Pierre Dramard, Marseille, France
Received 13 June 2001;
received in revised form 17 August 2001;
accepted 22 August 2001.
Corresponding author. Tel.:+33-491-74-47-36; fax:+33-491-75-11-31
e-mail: fbarlesi{at}mail.ap-hm.fr
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Abstract
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Objective: Bronchioloalveolar lung carcinoma (BAC) is characterized by bronchial and lymphatic dissemination explaining multifocal and bilateral spreading. Bilateral BAC is usually considered as a contraindication to surgery. Regarding poor efficacy of symptomatic and oncological treatments, we hypothesized that surgery might play a role to palliate hypoxemia associated with serious intrapulmonary shunting, as well as continuous bronchorrhea. Methods: We retrospectively studied here four consecutive patients, who underwent palliative pneumonectomy. Results: The shunt was confirmed again at the time of the surgery by a pulmonary artery occlusion demonstrating immediate improvement in arterial oxygen saturation from 89% at baseline to 98% after occlusion. Lung resections consisted of a left pneumonectomy in three cases and a right pneumonectomy in one. PaO2 levels under 5 l/min oxygen therapy improved dramatically when comparing preoperative data (mean 50.5 mmHg) to post-operative results (mean 150 mmHg). One patient died postoperatively. Three patients, who experienced an uneventful immediate post-operative course, received chemotherapy after surgery. Improvement of quality of life is testified by the absence of both symptoms and any need for oxygen therapy for few months. Disabling symptoms reappeared at 1, 8 and 10 months. Survival of these patients was 3, 12 and 18 months. Conclusions: These results support the interest of consideration of a surgical resection for highly selected patients presenting with bilateral BAC and severe intrapulmonary shunting.
Key Words: Bronchioloalveolar carcinoma • Pulmonary shunt • Hypoxemia • Surgery
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1. Introduction
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Bronchioloalveolar lung carcinoma (BAC) is a rare form of non-small-cell lung cancer and despite an increasing frequency over the past few decades [1], this subtype of adenocarcinoma accounts for only 3–4% of cases of non-small-cell lung cancer [2,3]. BAC has variable histopathological, radiological and clinical expressions [4], but the original feature of this type of lung cancer is the intrapulmonary dissemination of the disease due to bronchial or lymphatic spread, leading to a high frequency of multifocal and bilateral presentations. A more favorable prognosis is reported for patients with Clara cell than with mucin-producing cell tumors [5]. However, prognosis in BAC is undoubtedly dependent on the extension of the disease and is more favorable for patients with strictly localized BAC [6], for which surgery, when possible, is the standard therapeutic option [6].
In contrast, diffuse BAC should be regarded as a metastatic disease, associated with a 4-month median survival time [7]. Thus, palliation of disabling symptoms associated with the disease is still a common objective in the treatment proposed for lung cancer and especially BAC patients. Few medical tools are available for an efficient palliation of respiratory distress often characterizing patients with BAC. Therapeutic possibilities include symptomatic, oncological and sometimes surgical treatments. Oral erythromycin or inhaled indomethacin could inhibit bronchial hypersecretion, and, accordingly, might sometimes result in a marked reduction in the volume of sputum [8,9]. While BAC is usually reported as chemoresistant tumor, the efficacy of cisplatin in this subtype of adenocarcinoma is in fact comparable to that of chemotherapy in the treatment of metastatic adenocarcinoma of the lung [10]. Tendency of BAC to metastasize widely throughout the bronchus, but less commonly elsewhere, combined with the inefficiency of medical treatments, justified attempts at lung transplantation [11]. Long term results of the transplantation in this indication are disappointing since recurrence of the original tumor within the donor lungs is common [12,13].
On the basis of these arguments, we hypothesized that surgery might be of some interest for patients with extensive loco-regional disease accompanied by significant intrapulmonary shunting [14]. Aim of this surgery should be the palliation of hypoxemia and relief of some disabling symptoms such as continuous bronchorrhea and dyspnea. We thus report our experience with four consecutive patients who presented with bilateral lesions, refractory hypoxemia and intense symptoms, who underwent pneumonectomy with a palliative intent.
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2. Materials and methods
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We retrospectively studied four consecutive patients having about the same clinical presentation admitted for a diffuse BAC and operated at our institution during the year 1999. All were very symptomatic with stage IV dyspnea, continuous bronchorrhea, and severe refractory hypoxemia. Attempted palliative therapies had failed to improve their condition, including physiotherapy, inhaled therapy in all cases and a platinum-based chemotherapy in one. The ineffectiveness of the medical regimen previously implemented, led us to propose a pulmonary resection. We checked these patients for the following information :- Confirmation of the histological diagnosis of BAC.
- Confirmation of bilateral involvement of the lung by computed tomographic (CT) scans.
- Oncological treatment administrated before surgery.
- Evaluation of respiratory function before (spirometry, arterial blood gas values, and estimation of the shunt fraction) and after surgery (arterial blood gas values).
- Evaluation of post-operative morbidity and mortality.
- Residual symptoms and survival.
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3. Results
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Four patients with bilateral BAC and documented shunting were operated at our institution in 1999. Patient's characteristics are summarized in Table 1. One patient had two courses of chemotherapy (Carboplatin, AUC 5 and Paclitaxel, 175 mg/m2, D1–D1=21 days) without objective response, before being referred to our hospital.
Evaluation of respiratory function before resection is summarized in Table 2 (mean of PaO2, 50.5 mmHg). This evaluation was performed under 5 L/min oxygenotherapy. Clinical status of these patients was too critical to permit an evaluation of PaO2 and saturation without supplement of O2.
All four patients had bilateral lesions but involving predominantly one of the two lungs as shown in Fig. 1
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All four patients were informed of the palliative value of the proposed surgery. The shunt was confirmed at the time of the surgery and before the lung resection by a pulmonary artery occlusion, demonstrating immediate improvement in arterial oxygen saturation from 89% at baseline to 98% after occlusion.
The lung resection consisted of a left pneumonectomy in three cases, and a right pneumonectomy in one case. One patient had mediastinal nodal involvement (pN2 disease). The histological slides were reviewed and showed BAC with mucin-producing cell tumors in each case.
All patients were extubated immediately after the surgical procedure in the operating room. For three patients, post-operative course was uneventful. One patient died at day 21 of myocardial infarction complicating an extensive pneumonia of the remaining lung.
Post-operative blood gas analysis under 5 L/min are given in Table 3 (mean of PaO2, 150 mmHg). All patients who survived the operation were discharged from hospital without need for oxygen therapy. Because of the controlateral involvement, all of them received chemotherapy in the month following surgery. This treatment was a platinum-based regimen in all cases (Cisplatin, 100 mg/m2, day 1, and weekly Vinorelbine, 25 mg/m2, D1–D1=28 days for two patients, and Carboplatin AUC 4 and weekly Vinorelbine 25 mg/m2, D1–D1=28 days, for the other one). Further adaptations of the treatment were made in keeping with the toxicities. Patients received a mean of six courses of chemotherapy.
The outcome is detailed in Table 4. Respiratory symptoms reappeared at 1, 8 and 10 months, with need for permanent oxygen therapy again. The survival of these patients was 3, 12 and 18 months.
During the previous 5-year period, seven patients with bilateral BAC and similar features were referred to our institution. All died from respiratory failure. The survival of these patients was from 1 to 11 months (mean of 6.4 months).
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4. Discussion
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In the disappointing context of the treatment of bilateral BAC, we report highly selected patients who underwent palliative pneumonectomy. These patients had bilateral forms of BAC, with unequal radiological involvement of the lungs, leading to refractory hypoxemia and disabling symptoms. The shunt was confirmed before pulmonary resection by occlusion of pulmonary artery (mean of SaO2 before, 89% and 98% after occlusion). In three cases, surgical resection improved control of respiratory symptoms. The pneumonectomy produced the expected effect against shunting in all these three patients who showed immediate improvement of PaO2 (mean of 50.5–150 mmHg under 5 L/min oxygen therapy). The possibility of an arrest of the oxygen therapy, during few months in two cases after pneumonectomy, should be interpreted as an improvement in the quality of life. Survivals of 3, 12 and 18 months for bilateral BAC should be considered as an appreciable result.
Extra-thoracic dissemination remains anecdotal. A real drowning often characterizes the final evolution of bilateral forms. Many efforts are made, often unsuccessfully, to improve symptoms of these patients [8,9]. However, an effective treatment for bronchorrhea and severe dyspnea in these patients has not been yet established. Chemotherapy based treatment could be considered, but often has poor efficacy [10]. Alternative treatment as surgery for patients with bilateral BAC was proposed, including bilateral lung sparing resections whenever possible and lung transplantation [11], the later with always-discussed long term results [12,13]. Improvement of symptoms after pneumonectomy was probably better, in three of our patients, than that usually offered by symptomatic [8,9] or oncological regimens [10,15], even if effects of chemotherapy on respiratory symptoms are poorly described in these published studies. These results support those reported for unilateral cancer with massive intrapulmonary shunting [14,16]. Improvement in the quality of life is unfortunately not confirmed by a quality of life questionnaire. However, it was certainly the case, at minimum regarding freedom from supplemental oxygen. The morbidity rate associated with surgery for unilateral BAC ranges from 20 to 45% [6,17]. Probably because of the highly selective nature of patients reported here, three patients who underwent this surgery had simple post-operative courses. However, one should point out that one patient died postoperatively at day 21. Initial good results obtained with the first patients led us to propose surgery despite his past medical history of two myocardial infarctions. Excluding this patient, survival of operated patients was 3, 12 and 18 months, with a length of 1, 8 and 10 months with minimal symptoms and without any need of oxygen therapy. This result should be compared to the survival of patients with bilateral BAC, treated with chemotherapy alone, either at our institution (6.4 months), or reported in the literature (4–15 months) [10,15,18]. Despite the difficulty of such a comparison, survival of patients who underwent palliative pneumonectomy does not seem to be worse.
Such surgery is clearly not to be a standard of practice. Regarding our results, palliative pneumonectomy is possible but difficult weapon in the treatment of disabling symptoms from bilateral BAC. Palliative pneumonectomy for BAC with unequal involvement of the lung and severe intrapulmonary shunt support its interest only for very highly selected patients. Functional evaluation is essential. Selective occlusion of the pulmonary artery of the most involved lung using a Swan-Ganz catheter demonstrating immediate improvement in arterial oxygen saturation, could be useful before surgery. However, to a great extent, its success is based on the critical selection of candidates for this surgery, and co-morbidity, especially cardiovascular pathology, has to be a definitive exclusion criteria. Thus, palliative pneumonectomy has to be discussed in a multidisciplinary manner, with physiologists, oncologists and thoracic surgeons. Progress in the treatment of BAC through the use of new drugs could improve the control of symptoms of these patients in the future, but the actual poor efficacy of symptomatic and oncological regimens lead to consider all the therapeutic possibilities, including palliative pneumonectomy.
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5. Conclusion
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Surgical management of patients presenting with bilateral BAC with unequal involvement of the lungs and major hypoxemia in relation to a severe intrapulmonary shunting should not be denied systematically. Both symptoms and respiratory function could be improved postoperatively with tolerable morbidity and comparable survival to the patients treated with chemotherapy. Such a surgery should be discussed in a multidisciplinary manner and has to be considered exclusively for very highly selected patients. This may be of paramount importance in the context of a highly disabling and life-limiting disease.
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References
|
|---|
-
Barsky S.H., Cameron R., Osann K.E., Tomita T., Holmes E.C. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer 1994;73:1163-1170.[Medline]
-
Travis W.D., Travis L.B., Devesa S.S. Lung cancer. Cancer 1995;75(suppl.):191-202.[Medline]
-
Dumont P., Gasser B., Rouge C., Massard G., Wihlm J.M. Bronchioloalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically treated patients. Chest 1998;113:391-395.[Abstract/Free Full Text]
-
Harpole D.H., Bigelow C., Young W.G., Jr, Wolfe W.G., Sabiston D.C., Jr Alveolar cell carcinoma of the lung: a retrospective analysis of 205 patients. Ann Thorac Surg 1988;46(5):502-507.[Abstract]
-
Manning J.T., Spjut H.J., Tschen J.A. Bronchioloalveolar carcinoma: the significance of two histologic types. Cancer 1984;54:525-534.[Medline]
-
Daly R., Trastek V., Pairolero P., Murtaugh P.A., Huang M.S., Allen M.S., Colby T.V. Bronchioloalveolar carcinoma: factors affecting survival. Ann Thorac Surg 1991;51:368-377.[Abstract]
-
Hsu C.P., Chen C.Y., Hsu N.Y. Bronchioloalveolar carcinoma. J Thorac Cardiovasc Surg 1995;110:374-381.[Abstract/Free Full Text]
-
Suga T., Sugiyama Y., Fujii T., Kitamura S. Bronchioloalveolar carcinoma with bronchorrhoea treated with erythromycin. Eur Respir J 1994;7:2249-2251.[Abstract]
-
Homma S., Kawabata M., Kishi K., Tsuboi E., Narui K., Nakatani T., Nakata K. Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma. Chest 1999;115:1465-1468.[Abstract/Free Full Text]
-
Feldman E., Eeagan R., Schaid D. Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognostic. Mayo Clin Proc 1992;67:27-32.[Medline]
-
Etienne B., Bertocchi M., Gamondes J.P., Wiesendanger T., Brune J., Mornex F. Successful double-lung transplantation for bronchioloalveolar carcinoma. Chest 1997;112:1423-1424.[Abstract/Free Full Text]
-
Garver R.I., Zorn G.L., Wu X., McGiffin D.C., Young K.R., Jr, Pinkard N.B. Recurrence of bronchioloalveolar carcinoma in transplanted lungs. N Engl J Med 1999;340:1071-1074.[Abstract/Free Full Text]
-
Paloyan E.B., Swinnen L.J., Montoya A., Lonchyna V., Sullivan H.J., Garrity E. Lung transplantation for advanced bronchioloalveolar carcinoma confined to the lungs. Transplantation 2000;69:2446-2448.[Medline]
-
Chetty K.G., Dick C., McGovern J., Conroy R.M., Mahutte C.K. Refractory hypoxemia due to intrapulmonary shunting associated with bronchioloalveolar carcinoma. Chest 1997;111:1120-1121.[Abstract/Free Full Text]
-
Edwards C.W. Alveolar carcinoma: a review. Thorax 1984;39:166-174.[Medline]
-
Fishman H.C., Danon J., Koopot N., Langston H.T., Sharp J.T. Massive intrapulmonary venoarterial shunting in alveolar cell carcinoma. Am Rev Respir Dis 1974;109:124-128.[Medline]
-
Greco R.J., Steiner R.M., Goldman S., Cotler H., Patchefsky A., Cohn H. Bronchioloalveolar cell carcinoma of the lung. Ann Thorac Surg 1986;41:652-656.[Abstract]
-
Breathnach O.S., Ishibe N., Williams J., Linnoila R.I., Caporaso N., Johnson B.E. Clinical features of patients with stage IIIB and IV bronchioloalveolar carcinoma of the lung. Cancer 1999;86:1165-1173.[Medline]
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Abstract
1. Introduction
