Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?

BACKGROUND: Patients receiving chemotherapy for lung cancer usually modify their lung function during treatment with increases in forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) and decreases in lung diffusion for carbon monoxide (DLCO). This prospective study was designed to evaluate functional changes in forced expiratory volume in 1 second, forced vital capacity, and DLCO after three courses of induction chemotherapy with cisplatinum and gemcitabine in stage IIIa lung cancer patients and to assess their impact on respiratory complications after lung resection. METHODS: From March 1998 to January 2001, 30 consecutive patients with N2 nonsmall cell lung cancer had surgical resection after neoadjuvant treatment. Pre-chemotherapy and postchemotherapy results of standard respiratory function tests and DLCO were compared in patients with and without postoperative respiratory complications. RESULTS: All 30 patients completed the chemotherapy protocol without respiratory complications. Significant improvements (p < 0.05) were recorded after chemotherapy in transition dyspnea score, PaO(2) (mean value from 79.8 to 86.4 mm Hg), forced expiratory volume in 1 second % (from 78.1% to 87.5%) and forced vital capacity % (from 88.1% to 103.3%). Lung diffusion for carbon monoxide was significantly impaired after chemotherapy (from 74.1% to 65.7%; p = 0.0006), as well as DLCO adjusted for alveolar volume (from 92.8% to 77.4%; p < 0.0001). One patient died after surgery and 4 patients (13.3%) experienced postoperative respiratory complications. Compared with patients without complications, these 4 patients had higher mean increase in FEV(1) after chemotherapy (+26.8% vs + 6.7%; p = 0.025), but greater mean decrease in DLCO/Va (-27.8% vs -13.6%; p = 0.03). Impact of change in DLCO on postoperative respiratory complications was not confirmed by multiple logistic regression analysis (p = 0.16). CONCLUSIONS: In lung cancer patients, forced expiratory volume in 1 second and forced vital capacity assessed after neoadjuvant chemotherapy are not reliable indicators of the likelihood of respiratory complications after surgery. The risk of respiratory complication may be directly linked to loss of DLCO/Va. Lung diffusion for carbon monoxide assessed after neoadjuvant chemotherapy is probably the most sensitive risk indicator of respiratory complications after surgery. We recommend that DLCO studies be performed before and after chemotherapy in lung cancer patients undergoing induction therapy.     

Capillary zone electrophoresis as a tool to monitor the last stages of the degradation of water-sensitive polymers

In order to monitor the formation of the water-soluble by-products from chain-scission of degradable polymers used in the biomedical field, four capillary electrophoresis methods are discussed with the aim of giving the limits and performance for each. Three of them (electroosmotic flow reversal by dynamic adsorption of a polycation, multilayer polyelectrolyte coatings and physical binding of polyethylene oxide) are based on the use of dynamic coatings onto the inner surface of a fused silica capillary, a simple means to adapt performance to specific separations via modification and control of the electroosmotic flow of fused capillary. Using oligomers of lactic acid considered as standards the methods are compared. Other examples of ester-containing macromolecules (poly(hydroxybutyrate)), as well as degradable polyanions are described, namely N-acetylneuraminate polymer and poly(beta-malic acid).     

Peptide receptor radiotherapy: a new option for the management of aggressive fibromatosis on behalf of the Italian Sarcoma Group

The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with (90)Y-DOTATOC. (90)Y-DOTATOC should be further investigated in this setting.     

Pharmacogenetics of anticancer drug sensitivity in non-small cell lung cancer

In mammalian cells, the process of malignant transformation is characterized by the loss or down-regulation of tumor-suppressor genes and/or the mutation or overexpression of proto-oncogenes, whose products promote dysregulated proliferation of cells and extend their life span. Deregulation in intracellular transduction pathways generates mitogenic signals that promote abnormal cell growth and the acquisition of an undifferentiated phenotype. Genetic abnormalities in cancer have been widely studied to identify those factors predictive of tumor progression, survival, and response to chemotherapeutic agents. Pharmacogenetics has been founded as a science to examine the genetic basis of interindividual variation in drug metabolism, drug targets, and transporters, which result in differences in the efficacy and safety of many therapeutic agents. The traditional pharmacogenetic approach relies on studying sequence variations in candidate genes suspected of affecting drug response. However, these studies have yielded contradictory results because of the small number of molecular determinants of drug response examined, and in several cases this approach was revealed to be reductionistic. This limitation is now being overcome by the use of novel techniques, i.e., high-density DNA and protein arrays, which allow genome- and proteome-wide tumor profiling. Pharmacogenomics represents the natural evolution of pharmacogenetics since it addresses, on a genome-wide basis, the effect of the sum of genetic variants on drug responses of individuals. Development of pharmacogenomics as a new field has accelerated the progress in drug discovery by the identification of novel therapeutic targets by expression profiling at the genomic or proteomic levels. In addition to this, pharmacogenetics and pharmacogenomics provide an important opportunity to select patients who may benefit from the administration of specific agents that best match the genetic profile of the disease, thus allowing maximum activity.     

Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.