Alfonso Fiorelli

Control of post-thoracotomy pain by transcutaneous electrical nerve stimulation: effect on serum cytokine levels, visual analogue scale, pulmonary function and medication

OBJECTIVES Transcutaneous electrical nerve stimulation (TENS) has been used to control post-thoracotomy pain with contrasting results. We aimed to assess the efficacy of TENS on post-thoracotomy pain in relation of four criterion measurements as: (i) cytokines; (ii) pain; (iii) respiratory function and (iv) intake of narcotic medication. METHODS Between January 2008 and October 2010, 58 patients underwent standard posterolateral thoracotomy for resectable lung cancer. Fifty patients were enrolled in the present study and randomized in two groups: TENS group (25 patients) who received postoperatively TENS for 5 days and placebo group (25 patients) without TENS. In both groups (i) serum cytokines (IL-6, IL-10, TNF-α) were measured by ELISA before surgery and at 6, 12, 24, 48, 72, 96 and 120 postoperative hours (POHs); (ii) at the same POHs, the pain score was measured using visual analogue scale (VAS) ranging from 0 to 10 levels; (iii) respiratory function (FEV 1% and FVC % of predicted value) were valuated on 72, 96 and 120 POHs; (iv) the total intake of narcotic medication given during postoperative period of 5 days was recorded. Repeated measures of analysis of variance assess the difference between two study groups. A value of P < 0.05 was considered statistically significant. RESULTS Of the 50 patients enrolled, two patients of TENS group and two patients of the placebo group were lost to follow-up. (i) Serum IL-6 (P = 0.001), IL-10 (P = 0.001) and TNF-α (P = 0.001) levels in TENS group were significantly lower than in the control group; (ii) VAS score in TENS group was significantly lower than in the control group (P < 0.001); (iii) recovery of FEV 1 (P = 0.02) and of FVC (P = 0.02) was statistically better in the TENS group than in control group; (iv) morphine requirement was lower in the TENS group with respect to placebo TENS (P = 0.004). After 48 POHs, no patient required supplementary dose of morphine. TENS group compared with placebo-group presented a significant reduction of non-opioid consumption (P = 0.002). CONCLUSIONS TENS is a valuable strategy to alleviate post-thoracotomy pain with reduction of cytokine production and of analgesic consumption, and with positive effects on pulmonary ventilation function.

Endobronchial treatment of giant emphysematous bullae with one-way valves: a new approach for surgically unfit patients

OBJECTIVE We aimed to evaluate the feasibility and short-term efficacy of endobronchial treatment with one-way valves for giant emphysematous bulla in surgically unfit patients. METHODS Nine consecutive patients with giant emphysematous bulla were enrolled in the last 3 years. Endobronchial valves were placed in the segmental bronchi to functionally isolate the airway that supplied the bulla, favouring the deflation of the bulla and its atelectasis. Mean value ± standard deviation of forced expiratory volume in 1s (FEV1), preoperative forced vital capacity (FVC) and residual volume (RV) were: 1.0 ± 0.2l (35 ± 9.9%), 1.5 ± 0.5l (42 ± 12%) and 5.5 ± 0.7 l (23 1 ± 32%), respectively; and the values for diffusion capacity for carbon monoxide was 31 ± 4.6% and for the 6-min walk test (6 MWT) was 156 ± 92 m); all patients required supplemental oxygen at rest. The St. Georges Respiratory Questionnaire (SGRQ) score was 85 ± 4.6. RESULTS At 24-48 h after the procedure, the mean value of FEV1 (from 35% to 47%, p < 0.01), FVC (from 42% to 52%, p < 0.01), diffusion lung capacity for carbon monoxide (DLCO) (from 31% to 33%, p < 0.05) and 6 MWT (from 156 m to 281 m, p < 0.01) significantly improved with respect to baseline value. Conversely, mean value of total lung capacity (TLC) (from 157% to 123%, p < 0.01) RV (from 231% to 158%, p < 0.01) and SGRQ score (from 85 to 37, p < 0.01) was significantly lower than baseline data; these changes were preserved during the entire follow-up. CONCLUSION Our preliminary data confirm the feasibility and the potential efficacy of this strategy with significantly immediate improvement of respiration and quality of life, which remains stable during 6 months of follow-up.

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

Purpose: Resistance to tyrosine kinase inhibitors (TKI) of EGF receptor (EGFR) is often related to activation of other signaling pathways and evolution through a mesenchymal phenotype. Experimental Design: Because the Hedgehog (Hh) pathway has emerged as an important mediator of epithelial-to-mesenchymal transition (EMT), we studied the activation of Hh signaling in models of EGFR-TKIs intrinsic or acquired resistance from both EGFR-mutated and wild-type (WT) non–small cell lung cancer (NSCLC) cell lines. Results: Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-mutated HCC827-GR cells, we found SMO (the Hh receptor) gene amplification, MET activation, and the functional interaction of these two signaling pathways. In HCC827-GR cells, inhibition of SMO or downregulation of GLI1 (the most important Hh-induced transcription factor) expression in combination with MET inhibition exerted significant antitumor activity. In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibition of SMO and EGFR exerted a strong antiproliferative activity with a complete inhibition of PI3K/Akt and MAPK phosphorylation. In addition, the inhibition of SMO by the use of LDE225 sensitizes EGFR-WT NSCLC cells to standard chemotherapy. Conclusions:This result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. Clin Cancer Res; 21(20); 4686–97. ©2015 AACR.

Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications

Our goal was to determine the role of vascular endothelial growth factor (VEGF) in diagnosing of pleural effusion (PE) in order to select patients deserving of more aggressive procedures. Seventy-nine consecutive patients with undiagnosed unilateral PE were enrolled. Pleural VEGF levels, measured using enzyme-linked immunosorbent assay (ELISA), were correlated to etiology of PEs and other markers (protein, lactic dehydrogenase, amylase, glucose). The median level of VEGF in exudates (n=65) was significantly higher than that in transudates (P=0.0001) and among exudates, it was significantly higher in malignant (n=49) than that in benign exudates (P=0.005). No significant differences were observed between malignant effusions due to lung cancer (n=11) and other malignant effusions [mesothelioma (n=13) and/or extra-thoracic cancer]. Among all variables evaluated, logistic regression found that only VEGF was significantly correlated with the presence of malignant disease (P=0.002). Analysis of the receiver operating characterists (ROC) curves showed that the areas under the curve of VEGF were significantly larger than that of amylase (P=0.02), glucose (P=0.01), lactic dehydrogenase (P=0.001) and protein (P=0.01). VEGF increased the diagnostic rate of cytological examination by 24%. VEGF may represent a helpful adjunct to conventional diagnostic tools in ruling out malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Iatrogenic Air Leak Successfully Treated by Bronchoscopic Placement of Unidirectional Endobronchial Valves

This report describes a patient with persistent air leak after inadvertent placement of a chest drain in a bulla. Chest drain and suction failed to stop the air leak, whereas the surgical repair was judged to be excessively aggressive. In closure, two large endobronchial valves were sequentially positioned in the superior and inferior division of the left upper lobe to completely close it. The result was the collapse of bulla with closure of fistula and complete lung expansion.

A simple technique to control placement of Dumon stent in subglottic tracheal stenosis

Airway stenting is the chosen treatment for patients affected by subglottic tracheal stenosis and unfit for surgery. Among the different types of prostheses, the Dumon stent is a valid option especially in patients without tracheotomy. Insertion is usually achieved by pushing the stent off from a loader using a prosthesis pusher. If the stent is expelled below the stenosis, rigid forceps grasping the proximal end of the stent retract it above the stenosis. However, in difficult cases such as rigid stenosis with a luminal diameter smaller than the profile of the stent, such a manoeuvre may be difficult in non-expert hands. Thus, we proposed a simple and safe technique to facilitate the placement of a Dumon stent. We passed a long thread from outside to the inside of the stent. After the dilatation of the stenosis, the stent was pushed and, if needed, easily retracted with the thread into the proper position to ensure airway patency and to avoid migration. In addition, our procedure could be useful also to rapidly remove the stent if its size turned out to be inaccurate for the stenosis. With such a simple method we successfully treated 7 consecutive patients affected by complex subglottic stenosis and unfit for surgery.

Pre-emptive local analgesia in video-assisted thoracic surgery sympathectomy.

OBJECTIVE Our goal is to determine whether infiltration with a short-acting local anaesthetic such as lidocaine before the surgical incision has a pre-emptive effect on postoperative pain intensity and on incidence of paraesthesia in patients undergoing standard thoracoscopic sympathectomy for palmar hyperhidrosis. MATERIAL AND METHODS This prospective study includes a consecutive series of 18 patients undergoing bilateral standard thoracoscopic sympathectomy for palmar hyperhidrosis during January 2005-December 2007. Each patient enrolled in the study was randomised to receive pre-incisional lidocaine with epinephrine infiltration of the wounds on the one side, and normal saline solution on the other. The identical surgery was performed on each side to allow patients to act as their own controls. Then, the side which received local analgesia was compared with the control side with regard to pain control and paraesthesia after 4, 24 and 168 h postoperatively. The patients and investigators were both blinded concerning the side randomised to receive pre-emptive local analgesia (PLA). RESULTS We found that patients reported significantly less pain on the side treated with pre-emptive local anaesthesia in contrast to the control side 4 and 24h after surgery (p=0.001 and p=0.004, respectively). However, that difference decreased with time and was no longer significant 168 h following surgery (p=0.156). Regarding the paraesthesia, the incidence was higher in the control side than the PLA side at 4, 24 and 168 h postoperatively, but the difference was not statistically significant. A total of 17 of 18 (94%) patients noted a change in palmar hyperhidrosis status after surgery. CONCLUSION Our study shows that the pre-injection of local anaesthetic before standard thoracoscopic sympathectomy suppresses the local pain mediators, hence resulting in significantly less pain in the first postoperative 24 h but not thereafter. The clinical impact of the procedure is the possibility of early discharge to home and early return to work with potential economical benefits. However, because of the small number of patients, further studies are needed to corroborate our results.

Does cannabis smoking predispose to lung bulla formation

Objective The data of a consecutive series of habitual marijuana smokers were retrospectively evaluated and compared with that of non-marijuana smokers to assess differences between the 2 groups. Methods 13 consecutive habitual marijuana smokers were referred for treatment of spontaneous pneumothorax. The demographic, clinical, radiological, and pathological findings of these patients were reviewed and compared with 140 non-marijuana smokers treated for the same pathology at the same time. Results Bullae were seen in 8/13 (62%) and 110/140 (78%) of marijuana smokers and non-marijuana smokers, respectively. However, when patients less than 35-years old were considered, the incidence of bulla was higher in marijuana smokers than non-marijuana smokers (7/10 vs. 3/10, p < 0.05). The pathological findings showed a greater presence of inflammatory cells in specimens from marijuana smokers than those of non-marijuana smokers (8/11 vs. 2/42, respectively, p < 0.05). No significant differences in hospital stay and clinical outcome were registered between the 2 groups. Conclusions Despite the fact that we were unable to demonstrate that marijuana had a causal role in the development of emphysema, our study showed that marijuana smokers had a higher incidence of inflammatory cells in pathological specimens, which may favor lung injury, thus predisposing to bulla formation.

The influence of body mass index and weight loss on outcome of elderly patients undergoing lung cancer resection.

BACKGROUND The aim of the study was to evaluate the influence of nutritional status on outcome of elderly patients resected for lung cancer. MATERIALS AND METHODS A total of 117 consecutive patients aged ≥ 70 years undergoing lung cancer resection were enrolled. In addition to routine preoperative evaluations, other variables such as body mass index, weight loss, serum albumin, lymphocytes, and transferrin were counted. According to the body mass index value, patients were divided into Group A (≤ 18.5, underweight) and Group B (> 18.5) and risk factors for morbidity and mortality were analyzed. RESULTS Group A and Group B counted 21 and 96 patients, respectively. The mean age was 74.9 ± 2.6; body mass index of Group A was significantly lower than that of Group B (16.7 ± 1.3 vs. 23.5 ± 1.7, respectively, p < 0.0001). On multivariate analysis, significant risk factors for complications were pneumonectomy (p = 0.001), stage (p = 0.006), predictive postoperative flow expiratory volume in 1 second (ppoFEV1%) (p = 0.003), and coronary disease (p = 0.04) and significant risk factors for early mortality were pneumonectomy (p = 0.0002), ppoFEV1% (p < 0.0001), BMI (0.02), and weight loss (0.007). The median survival time of Group A and Group B was 41 versus 54 months, respectively (p = 0.1). However, body mass index of less than 18.5 (p = 0.01) and weight loss of > 5% before operation (p = 0.01) were independent risk factors for 1 year mortality. CONCLUSIONS In elderly patients, malnutrition was a significant additional risk factor for early death. Nutritional assessment should be included in the routine preoperative selection. In malnourished patients, nutritional support before and after operation and a careful postdischarge care might be beneficial, but it should be corroborated by further prospective studies.

Quantitative assessment of emphysematous parenchyma using multidetector-row computed tomography in patients scheduled for endobronchial treatment with one-way valves

OBJECTIVES To investigate the role of volume quantitative assessment using multidetector-row computed tomography to select patients scheduled for endobronchial one-way valves treatment. METHODS Twenty-five consecutive patients (15 with heterogeneous emphysema and 10 with giant emphysematous bulla) undergoing endobronchial valves treatment were enrolled. All patients were studied pre- and postoperatively with standard pulmonary functional tests and quantitative volume assessment of target lobe and entire lung. Emphysematous parenchyma was obtained applying density thresholds of -1.024/-950 Hounsfield units. Among different subtype of patients, we evaluated: (i) the differences between preoperative versus postoperative data; (ii) the correlation between functional and volumetric quantification changes and (iii) the critical threshold value of volumetric quantification of the target lobe in close association with clinical effects. RESULTS Among heterogeneous emphysematous and giant emphysematous bulla patients, a significant improvement of flow-expiratory volume in 1 s (from 36.9 ± 15.3 to 43.9 ± 10.4; P = 0.01; and from 35.8 ± 6.0 to 47.5 ± 7.9; P < 0.0001, respectively); and of forced vital capacity (from 41.9 ± 5.9 to 47.3 ± 9.3; P = 0.0009 and from 40.7 ± 5.9 to 48.8 ± 4.9; P = 0.0002, respectively); and a significant reduction of residual volume (from 185 ± 14 to 157 ± 14.7; P = 0.005; and from 196 ± 13.5 to 137 ± 21; P < 0.0001, respectively) and of total lung volume (from 166.7 ± 13 to 137 ± 18 ; P = 0.0003, and from 169 ± 15 to 134 ± 18; P < 0.0001, respectively) were seen after treatment. The volumetric measurements showed a reduction of volume of the treated lobe among heterogeneous emphysematous patients (from 1448 ± 204 to 1076 ± 364; P = 0.0008); and in those with giant emphysematous bulla (from 1668 ± 140 to 864 ± 199; P < 0.0001). The entire lung and target lobe volume changes were inversely correlated with change in forced expiratory volume in 1 s in patients with heterogeneous emphysematous (r = -0.7; P = 0.0006; and r = -0.7; P = 0.0009, respectively) and giant emphysematous bulla (r = -0.8; P = 0.001; and r = -0.7; P = 0.009, respectively). Among patients with heterogenous emphysematous and giant emphysematous bulla, the value of sensitivity and specificity were 66.6 and 83%, respectively (for a volumetric qunatification >1.5239), and of 60 and 100%, respectively (for a volumetric qunatification >1.762). CONCLUSIONS Our study showed that the volumetric quantification adds further informations to the routine evaluation for optimizing the selection of patients scheduled for endobronchial valve treatment.