Structural lung damage after chemotherapy fact or fiction?
BACKGROUND
The hypothesis that chemotherapy increases morbidity after pneumonectomy remains under debate, as the results of previous surgical series remain controversial. The hypothesis of the study is that patients who received preoperative chemotherapy may have subclinical parenchymal damage, increasing their risk of respiratory complications.


METHODS
The study population was composed of 10 patients who underwent pneumonectomy after chemotherapy for lung cancer (cisplatin+gemcitabine) randomly selected from our database and compared with 10 matched patients who underwent pneumonectomy without previous chemotherapy during the same period. Healthy lung tissue was obtained from surgical specimens, processed according to standard methods and evaluated on ematossilin and eosin-stained sections. Two pathologists without information on the preoperative treatment were asked to review the slides in order to reach a consensus on the type and extent of lung damage. Relevant information was then compared with functional tests and postoperative outcome.


RESULTS
Severe and diffuse (more than 50% of lung parenchyma) interstitial alterations were detected in the lungs of eight patients, seven of which belonged to the chemotherapy group (70%, p 0.02). Six of these patients developed postoperative respiratory complications. In the chemotherapy group, patterns of interstitial involvement were variable interstitial inflammation and fibrosis associated with obliterative bronchiolitis [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885-8], bronchiolitis obliterans-organizing pneumonia [Leo F, Solli P, Veronesi G, et al. Does chemotherapy increase the risk of respiratory complications after pneumonectomy? J Thorac Cardiovasc Surg 2006;132:519-23], diffuse alveolar damage [Novoa N, Varela G, Jimenez MF. Morbidity after surgery for non-small cell lung carcinoma is not related to neoadjuvant chemotherapy. Eur J Cardiothor Surg 2001;20:700-4], DIP (desquamative interstitial pneumonia)-like reaction [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885-8] and UIP (usual interstitial pneumonia)-like changes [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885-8]. The only preoperative clinical predictor of severe diffuse damage was preoperative diffusion by carbon monoxide (Dlco).


CONCLUSIONS
Preoperative chemotherapy is associated with an increased risk of severe and diffuse pulmonary disease even in the presence of normal spirometric parameters. These alterations may play an important role in the occurrence of postoperative respiratory complications.
Leo
Francesco
F
Division of Thoracic Surgery, European Institute of Oncology, Via Ripamonti 435, 20100 Milan, Italy. francesco.leo@ieo.it
Pelosi
Giuseppe
G
Sonzogni
Angelica
A
Chilosi
Marco
M
Bonomo
Guido
G
Spaggiari
Lorenzo
L
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011013:Pneumonectomy; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D057234:Preoperative Period; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine