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ABSTRACT: BACKGROUND: Surgical biopsy of interstitial lung disease (ILD) performed through general anesthesia and video-assisted thoracic surgery (VATS) is still associated with not negligible mortality and morbidity rates. We hypothesized feasibility and minimized side-effects of VATS lung biopsy performed by regional anesthesia methods in awake patients. METHODS: Thirty patients with clinical and radiologic diagnosis of undetermined ILD underwent awake VATS lung biopsy under thoracic epidural anesthesia (20 patients) or intercostal blocks (10 patients). Primary outcome was technical feasibility scored from 0 (not performed) to 4 (excellent). Cardiorespiratory variables, including the ratio of arterial oxygen to fraction of inspired oxygen (PaO(2)/FiO(2)) and arterial carbon dioxide (PaCO(2)) were also assessed at fixed time points. RESULTS: Mean age was 62 ± 10 years. No patient needed conversion to general anesthesia. The feasibility score was 3.4 ± 0.7. Feasibility score correlated with percent predicted diffusing capacity of lung for carbon monoxide (R = 0.67, p = 0.0001). Operative time and global in-operating room time (anesthesia time + operative time) was 22 ± 5 minutes and 47 ± 11 minutes, respectively. The average number of biopsies was 1.8 ± 0.4 per patient. There was no operative mortality and 1 minor complication (3.3%). Mean hospital stay was 1.4 ± 0.7 days and procedure-related cost was 2700 ± 472 euros. Both anesthesia methods resulted in optimal feasibility although by intercostal blocks procedure-related cost was lower (2,410 ± 337 vs 2,800 ± 486 euros, p < 0.002) than by epidural anesthesia. Precise histopathologic diagnosis was achieved in 29 (97%) patients. CONCLUSIONS: Our study has shown that in patients with ILD, awake VATS lung biopsy was easily feasible by regional anesthesia and resulted in low morbidity, excellent diagnostic yield, short hospital stay, and low cost.
The Annals of thoracic surgery 12/2012; · 3.74 Impact Factor
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Eugenio Pompeo
The Journal of thoracic and cardiovascular surgery 07/2012; 144(1):281-2; author reply 282. · 3.41 Impact Factor
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ABSTRACT: The study objective was to assess in a randomized controlled study (NCT00566839) the comparative results of awake nonresectional or nonawake resectional lung volume reduction surgery.
Sixty-three patients were randomly assigned by computer to receive unilateral video-assisted thoracic surgery lung volume reduction surgery by a nonresectional technique performed through epidural anesthesia in 32 awake patients (awake group) or the standard resectional technique performed through general anesthesia in 31 patients (control group). Primary outcomes were hospital stay and changes in forced expiratory volume in 1 second. During follow-up, the need of contralateral treatment because of loss of postoperative benefit was considered a failure event as death.
Intergroup comparisons (awake vs control) showed no difference in gender, age, and body mass index. Hospital stay was shorter in the awake group (6 vs 7.5 days, P = .04) with 21 versus 10 patients discharged within 6 days (P = .01). At 6 months, forced expiratory volume in 1 second improved significantly in both study groups (0.28 vs 0.29 L) with no intergroup difference (P = .79). In both groups, forced expiratory volume in 1 second improvements lasted more than 24 months. At 36 months, freedom from contralateral treatment was 55% versus 50% (P = .5) and survival was 81% versus 87% (P = .5).
In this randomized study, awake nonresectional lung volume reduction surgery resulted in significantly shorter hospital stay than the nonawake procedure. There were no differences between study groups in physiologic improvements, freedom from contralateral treatment, and survival. We speculate that compared with the nonawake procedure, awake lung volume reduction surgery can offer similar clinical benefit but a faster postoperative recovery.
The Journal of thoracic and cardiovascular surgery 11/2011; 143(1):47-54, 54.e1. · 3.41 Impact Factor
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ABSTRACT: In a prospective non-randomized study, we compared results and costs of non-resectional lung volume reduction surgery (LVRS) performed through awake or non-awake anesthesia that was freely chosen by recruited patients.
Non-resectional LVRS was performed by epidural anesthesia in 41 patients (awake group) and by general anesthesia in 19 patients (non-awake group). Perioperative outcome included analysis of oxygenation (PaO(2)/FiO(2)) at fixed time points and global time spent in the operating room (anesthesia plus surgery plus weaning plus recovery times). Costs were evaluated at discharge. Forced expiratory volume in 1s (FEV(1)), plethysmographic residual volume (RV(plet)) and maximal incremental treadmill test (MITT) score were assessed preoperatively and every 6 months, postoperatively.
Perioperative outcome was better in the awake group with better oxygenation 1h after the operation (P=0.004) and shorter global in-operating room stay (P<0.0001). There was no operative mortality. In the awake group, median hospital stay was shorter (6 days vs 7 days, P=0.006), whereas median hospital charges were lower than in the non-awake group (7800 euros vs 8600 euros, P=0.006). At 6 months, there was no difference (awake vs non-awake) in median ΔFEV (0.33l vs 0.28l, P=0.09), ΔRV (-0.99l vs -0.98l, P=0.95), and ΔMITT score (1.0 vs 0.75, P=0.31).
In our study, awake non-resectional LVRS was preferred by the majority of patients. It resulted in better perioperative outcome, shorter hospital stay, and lower costs than equivalent procedures performed by non-awake anesthesia. Six months' clinical results were comparable, showing that the awake approach had no impact on late clinical benefit.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2011; 39(4):e51-8. · 2.40 Impact Factor
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ABSTRACT: Staple excision of emphysematous bullae through general anesthesia is the standard surgical treatment of bullous emphysema. We have developed a new surgical technique entailing thoracoscopic bullaplasty performed in fully awake patients through sole epidural anesthesia.
This prospective nonrandomized trial included 35 patients undergoing awake thoracoscopic bullaplasty between 2002 and 2009. Preoperative work-up included computed tomography with algorithm for quantitative measurement of the bulla volume. Outcome measures included patient's satisfaction with the anesthesia, scored into four grades (1=unsatisfactory; 4=excellent); ratio of arterial oxygen tension to fraction of inspired oxygen (PaO(2)/FiO(2)), and postoperative assessment of standard clinical measures at 6, 12, and 36 months.
There were 29 men and six women with a median age of 60 years. Median volume of the bulla was 688 ml. Awake bullaplasty was successfully completed in 34 patients. Perioperatively, PaO(2)/FiAO(2) decreased significantly (analysis of variance (ANOVA), P<0.0001) though remaining satisfactory (>300 mmHg), whereas PaCO(2) increased intraoperatively (ANOVA, P<0.0001) but returned to baseline values 1h after surgery (P=0.20). There was no mortality; four patients had air leaks longer than 7 days. Mean hospital stay was 4.9 ± 2.2 days. Comparisons between pre- to 6-month changes in outcome measures showed improvements (P<0.0001) in forced expiratory volume in 1s (FEV(1)) (+0.37 l), residual volume (-1.16 l), dyspnea index (-2), and standard 6-min walk test (SMWT) (+71 m). These improvements lasted for up to 36 months and in no patient did operated bullae recur.
Our study suggests that awake thoracoscopic bullaplasty was well tolerated and easily performed in the majority of the patients, and significant clinical improvements lasted for up to 36 months.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2010; 39(6):1012-7. · 2.40 Impact Factor
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ABSTRACT: Surgical stress and general anesthesia can have detrimental effects on postoperative immune function. We sought to comparatively evaluate postoperative lymphocytes response in patients undergoing video-assisted thoracoscopic surgery (VATS) under thoracic epidural or general anesthesia.
Between October 2008 and June 2009, 50 patients with nonmalignant pulmonary conditions were randomized to undergo VATS through either sole epidural anesthesia and spontaneous ventilation (awake group, n = 25) or general anesthesia with one-lung ventilation (control group, n = 25). In both groups, assessment of total lymphocytes count and changes in proportion of lymphocyte subsets including CD19+, CD3+, CD4+, CD8+, CD4+:CD8+ ratio, and CD16+CD56+ (natural-killer cell) were evaluated by two-way analysis of variance test for repeated measures at baseline and postoperative days 1, 2, and 3. The Mann-Whitney test was performed at each time point only for significant parameters at between-group analysis of variance.
Comparisons of baseline data showed relatively homogeneous groups. Between-group analysis of variance was significant for proportion of natural-killer cells (p = 0.01). In particular, the control group disclosed a significantly lower median proportion of natural-killer cells as compared with the awake group on postoperative day 1 (5% interquartile range [IQR]: 3% to 8%] vs 12% [IQR: 8% to 14%], p = 0.003) and 2 (7% [IQR: 4% to 10%] vs 11% [IQR: 8% to 21%], p = 0.02). Total lymphocyte count was significantly decreased in the control group only (p < 0.00001). No difference was found between groups in the remaining lymphocyte subsets.
In this randomized study, awake VATS resulted in a lesser impact on postoperative lymphocyte responses than procedures performed under general anesthesia, as shown by the significant difference in postoperative proportion of natural-killer cells.
The Annals of thoracic surgery 09/2010; 90(3):973-8. · 3.74 Impact Factor
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ABSTRACT: Anterior mediastinal masses can develop from a wide spectrum of pathologic conditions, most of which are malignant in nature and require prompt diagnosis for immediate initiation of the appropriate treatment. Clinical pictures can be variable and complicated by associated intrathoracic conditions requiring surgical management such as pleural and pericardial effusions or nodules (complex anterior mediastinal masses). We have used a single-trocar video-assisted thoracoscopic surgery (VATS) approach using thoracic epidural or sole local anesthesia in awake patients. Advantages of awake VATS biopsy include avoidance of all potential adverse effects related to the use of general anesthesia, wide visual control of mediastinal sampling, and accurate assessment of the disease extent with the possibility of obtaining multiple biopsy specimens from different sites of the mass and a diagnostic yield of 100%. This novel and less invasive surgical option might thus be included within the framework of most reliable methods currently available to manage patients with undetermined anterior mediastinal masses.
Thoracic Surgery Clinics 05/2010; 20(2):225-33.
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ABSTRACT: Myasthenia gravis (MG) is an uncommon, organ-specific, autoimmune chronic neuromuscular disorder involving the production of autoantibodies directed against the nicotinic acetylcholine receptors (anti-AchRab). It is characterized by weakness and rapid fatigability of voluntary muscles. Thymectomy is performed early in the course of the disease and is indicated for adults less than 70 years old. For many years, the clinical efficacy of thymectomy has been questioned and so far, its benefits in nonthymomatous MG have not been firmly established. Furthermore, the precise mechanisms of action of thymectomy are unknown although possible explanations include removal of the source of continued antigen stimulation and of the AchRab-recruiting B-lymphocytes as well as immunomodulation. However, thymectomy remains indicated in patients with MG and is widely applied to increase the probability of improvement or remission. This article presents the evolution of technical and surgical advances achieved within the authors' program of extended endoscopically assisted thymectomy since 1995. The use of video-assisted thoracic surgery and its variants for performing thymectomy in MG patients is now well established and will continue to evolve for further improvement in the results.
Thoracic Surgery Clinics 05/2010; 20(2):253-63.
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ABSTRACT: Surgical treatment of idiopathic scoliosis has classically included posterior, anterior, or combined open surgical techniques. In recent years, a videothoracoscopic approach to the spine has been increasingly employed either in combination with the posterior open approach or as a stand-alone treatment including anterior release and fusion. Proponents of videothoracoscopic approaches believe that they allow clinical outcomes comparable to those of open surgery with minimized surgical trauma and postoperative pain, superior cosmetic effects, and less impairment of respiratory function. Periodic technological refinements continue to be proposed and are likely to render these surgical options simpler, safer, and more effective. This article reports on the current state of the art of the videothoracoscopic approaches most commonly employed for the surgical treatment of thoracic idiopathic scoliosis.
Thoracic Surgery Clinics 05/2010; 20(2):311-21.
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ABSTRACT: In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia.
To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation.
A total of 28 patients with moderate to severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared with 26 similar patients, who refused operation and followed a standardized rehabilitation program, and to a matched healthy group. Respiratory function, body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin levels were evaluated before and 12 months after treatment. Gene expression levels of inflammatory mediators and protease-antiprotease were assessed in emphysematous specimens from 17 operated patients by matching to normal tissue from resection margins.
Significant improvements were only obtained after surgery in respiratory function (FEV(1), +25.2%, P < 0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P < 0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P < 0.001). Supportive gene expression analysis demonstrated active inflammation and protease hyperactivity in the resected emphysematous tissue. Reduction of TNF-alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001, respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02, and P = 0.09, respectively).
LVRS significantly reduced circulating inflammatory mediators and increased antiprotease levels over respiratory rehabilitation, also improving respiratory function and nutritional status. Correlations of inflammatory mediators and antiprotease levels with RV and, partly, with body composition suggest that elimination of inflammatory emphysematous tissue may explain clinical improvements after surgery.
American Journal of Respiratory and Critical Care Medicine 04/2010; 181(8):806-14. · 11.08 Impact Factor
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Eugenio Pompeo
The Annals of thoracic surgery 03/2010; 89(3):875-6. · 3.74 Impact Factor
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ABSTRACT: The expression of cyclooxygenase-2 (COX-2) and cell-cycle proteins (p21 and p27) proves useful in predicting prognosis and orientating therapy in many malignant tumours. Malignant pleural mesothelioma is an uncommon and lethal cancer for which there are limited treatment options. In this study, we evaluated the impact on prognosis and the influence on therapeutic strategy of immunohistochemical expression of COX-2, p21 and p27 in specimens from patients treated for malignant pleural mesothelioma.
We retrospectively reviewed immunohistochemical expression of COX-2, p21 and p27 dichotomised into high and low expression from specimens of 77 consecutive patients undergoing biopsy-plus-pleurodesis (n=6), pleurectomy-decortication (n=44) or extrapleural pneumonectomy (n=27) operations for malignant pleural mesothelioma between 1987 and 2007. Histology was of epithelioid (n=50), biphasic (n=17) and sarcomatoid (n=10) subtypes. Tumour node metastasis (TNM)-stage was I (n=21), II (n=36) and III (n=20). Therapies used were sole adjuvant radiotherapy (n=17), adjuvant radio-chemotherapy (n=56) and neo-adjuvant chemotherapy plus adjuvant radiotherapy (n=4). From 2005 on, preoperative maximal standard uptake value (SUV(MAX)) was also measured by fluorodeoxyglucose positron-emission-tomography. Significance was investigated by Kaplan-Meier survival and Cox regression analysis.
The median survival was 10 months. Survival was negatively influenced by histology (epithelioid vs biphasic vs sarcomatoid) (p=0.009), positive macroscopic resection margins (p=0.016), metastatic mediastinal lymph nodes (p=0.016), high COX-2 (p=0.0001) expression, low p21 (p=0.0001) expression and low p27 (p=0.001) expression. Conversely, neither the type of surgery (biopsy-plus-pleurodesis vs pleurectomy-decortication vs extrapleural pneumonectomy), nor preoperative SUV(MAX) (> or = 6.0 vs <6.0), or combined therapies (sole radiotherapy vs adjuvant radio-chemotherapy vs neo-adjuvant chemotherapy plus adjuvant radiotherapy) reached a significant level of difference. Cox regression analysis showed that only immunohistochemical triple combination of high COX-2 and low p21 and p27 expression influenced survival (p=0.0001, hazard ratio 4.7, 95% confidence intervals 3-11) regardless of type of treatment.
At Cox regression analysis, a combination of high COX-2 and low p21 and p27 expression resulted in the only negative prognosticator of malignant pleural mesothelioma. With this combination, less aggressive surgical options might be preferred.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2010; 38(3):245-52. · 2.40 Impact Factor
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ABSTRACT: This study was undertaken to assess stress hormones response after awake videoassisted thoracoscopic surgery (VATS). Plasma levels of adrenal-corticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine, and glucose were assessed at baseline, 3 h postoperatively (T1), and on postoperative mornings 2 (T2) and 3 (T3) in 21 patients undergoing awake VATS with epidural anesthesia for non-malignant conditions (n=11) or equivalent procedures performed with general anesthesia. Epinephrine level peaked in both groups at T1, although significant change from baseline values occurred in the control group only [median-Delta: 6 ng/l (IQR: 4-6), P=0.005]. Cortisol level was lower in the study group at T1 (15.5 microg/dl vs. 23.0 microg/dl, P=0.001) and T2 (15.2 microg/dl vs. 19.2 microg/dl, P=0.002). In the control group, peak cortisol level proved not to be related to changes in ACTH (R=0.23, P=0.46). At T2, glucose (137 mg/dl vs. 98 mg/dl, P=0.01) and C-reactive protein (P=0.04) were higher in the control group. No other clinically relevant between-groups differences were found in aspecific acute-response factors. Overall, these preliminary findings suggest attenuated stress response after awake VATS in comparison with equivalent procedure performed under general anesthesia and one-lung ventilation.
Interactive cardiovascular and thoracic surgery 02/2010; 10(5):666-71.
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Rolando M D'Angelillo,
Lucio Trodella,
Marzia Ciresa,
Francesco Cellini,
Michele Fiore,
Carlo Greco, Eugenio Pompeo,
Tommaso Claudio Mineo,
Laura Paleari,
Pierluigi Granone,
Sara Ramella,
Alfredo Cesario
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ABSTRACT: We report the results of a phase II trial exploring the efficacy and the feasibility of combination of gemcitabine and cisplatin concurrent with radiotherapy followed by surgery in patients with stage III non-small cell lung cancer.
Patients with histocytologically confirmed non-small cell lung cancer were treated with cisplatin 80 mg/sqm/wk of 1 and 4 or 20 mg/sqm/d of weeks 1 and 4 and weekly gemcitabine at 300 to 350 mg/m2 plus involved field radiotherapy. A 3D-conformal radiotherapy was delivered up to 50.4 Gy, with daily fractionation of 1.8 Gy. After clinical, radiologic, and pneumological reassessment, patients who reentered criteria for resectability were operated.
The stage at diagnosis was IIIA-N2 in 29 patients and IIIB-T4N0-2 for vascular direct infiltration for the remaining 21. Fifteen patients (30%) experienced acute grade 3 to 4 hematological toxicity, whereas acute grade 3 esophageal toxicity was recorded in three patients (6%). One patient developed a grade 4 pulmonary toxicity (2%). Clinical response was 40 (80%) partial response, one (2%) stable disease, and nine (18%) progressive disease. Thirty-six patients (72%) underwent surgery. Final pathology showed a downstaging to stage 0 to I in 25 cases (50%). Median overall survival for all patients was 21.8 months, with a 3-year survival of 40.2%.
The results of this phase II trial confirm the feasibility and the efficacy of concurrent chemoradiotherapy followed by surgery.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2009; 4(12):1517-23. · 4.55 Impact Factor
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ABSTRACT: Malignant pleural mesothelioma is highly aggressive and recurs rapidly despite radical multimodality treatment. Progression of mesothelioma is thought to be governed by various growth factors, including vascular endothelial growth factor (VEGF). Placenta growth factor (PlGF) belongs to the VEGF family, although no study has yet investigated its expression in mesothelioma. We hypothesized that PlGF is overexpressed in mesothelioma and could have prognostic value in patients treated by extrapleural pneumonectomy.
We assessed by immunohistochemistry with semiquantitative classification (0 = no staining; 3 = strong staining), the expression levels of PlGF and its cognate receptors VEGF receptor 1, neuropilin-1, and neuropilin-2 in 27 patients with malignant pleural mesothelioma undergoing extrapleural pneumonectomy, in 14 patients with reactive mesothelium, and in 10 patients with normal mesothelium.
Whereas PlGF was not expressed in normal mesothelium, it was overexpressed (grade 3) more frequently in mesothelioma than in reactive mesothelium specimens (11 or 41% versus 1 or 7%, respectively, p = 0.03). Furthermore, in mesothelioma, VEGF receptor 1 and neuropilin-1 and -2 were overexpressed in 18 specimens (67%), 8 specimens (30%), and 9 specimens (33%), respectively. Mean survival after extrapleural pneumonectomy was 17 months. An inverse relationship was found between the degree of PlGF expression and survival in months (R = -0.45, p = 0.01). No correlation was found between tumor stage and survival (R = -0.33) and between tumor stage and PlGF expression (R = 0.07).
We have shown that PlGF can be overexpressed in malignant pleural mesothelioma. In addition, the finding of an inverse relationship between PlGF expression levels and survival suggests a pivotal role of this factor in the recurrence and progression of mesothelioma after extrapleural pneumonectomy.
The Annals of thoracic surgery 09/2009; 88(2):426-31. · 3.74 Impact Factor
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ABSTRACT: To evaluate feasibility, technical features and results of video-assisted pleural decortication for empyema thoracis performed in awake patients.
This retrospective analysis involved a cohort of 19 patients (median age: 58 years) undergoing awake video-assisted thoracoscopic pleural decortication under epidural anaesthesia (N=15) or paravertebral blocks (N=4) between March 2004 and September 2008. Baseline and perioperative data including degree of postoperative lung re-expansion at 48 h, hospital stay, morbidity rate and daily fluid loss were recorded. In addition, intra- and perioperative changes in main pathophysiological variables PaO(2)/FiO(2) ratio, PaCO(2), mean arterial pressure and heart rate were analysed.
Origin of the empyema was parapneumonic (N=14), post-traumatic (N=3) and cancer related (N=2). All patients underwent previous conservative management. The duration of the symptoms averaged 35 days (quartile range (QR): 28-40). Co-morbidities included chronic obstructive pulmonary disease (COPD) (N=4), HIV infection (N=1), diabetes mellitus (N=2) and cirrhosis (N=1). Operation was performed videothoracospically in 15 patients whereas four patients with major pleural thickening underwent awake lateral thoracotomy. Operative time averaged 50 min (QR: 40-70). Perioperative data analysis showed no intra-operative deterioration in arterial oxygenation (median-Delta: 0 mm Hg, QR: -5/+9, P=0.6). Transient permissive hypercapnia (<55 mm Hg) developed in three patients with no need of conversion to general anaesthesia. Median pain level assessed by a visual analogue score (VAS) 1h postoperatively was 4 (QR: 2-5), and it was significantly reduced on postoperative day 1 (median 3, QR: 2-4, P=0.03). There was neither mortality nor major morbidity. Hospitalisation averaged 6 days (QR: 5-7). At postoperative chest X-ray, lung re-expansion was rated as complete in 16 patients, satisfactory in (>80%) two patients and unsatisfactory in a 86-year-old patient with pleural mesothelioma who has the chest drain still in place 5 months after surgery. No patient had recurrence of the empyema at subsequent follow-ups.
In our study, awake video-assisted pleural decortication proved feasible and resulted in satisfactory lung re-expansion in 95% of the patients. We hypothesise that spontaneous ventilation facilitated both identification of the correct plane and dissection, thus resulting in lesser surgical injury on the underlying lung.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 09/2009; 37(3):594-601. · 2.40 Impact Factor
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ABSTRACT: Recurrent intrathoracic thymomas may have an unpredictable behavior. Cell-cycle protein expression has proven useful in predicting outcome in a variety of neoplasms. We investigated its potential prognostic importance in recurrent intrathoracic thymomas.
We reviewed the case histories of 25 consecutive patients operated on between 1987 and 2004 for intrathoracic recurrence (7 mediastinal, 18 nonmediastinal) after radical thymomectomy. Complete resection was performed in 14 patients. In the other 11 patients incomplete resection was followed by chemotherapy and radiotherapy. Expression of cell-cycle proteins (p53, p21, and p27) was assessed by immunohistochemistry in specimens retrieved from both initial and recurrent thymomas. Univariate and multivariate analysis for prognostic factors present at the time of the recurrence was performed.
Eight of 14 patients who underwent complete resection had a second recurrence after a mean free interval of 20 +/- 9 months, and a new complete resection was reperformed in 4. After incomplete resection, chemotherapy and radiotherapy allowed total remission in 4 subjects and only 1 of these had a second recurrence. Survival after surgery of the recurrence was negatively influenced by incomplete recurrence resection (P = .03), first disease-free interval less than 24 months (P = .03), high p53 (P = .04), low p21 (P = .02), low p27 (P = .003) expressions, and combination of these proteins (p53 high, p21 low, p27 low expression) (P = .0001). Multivariate analysis selected the triple combination of cell-cycle protein expression as the most significant prognostic variable (P = .02, odds ratio = 11.96, 95% confidence interval = 1.39-102.63).
Cell-cycle protein expression, and namely the combination of high p53, low p21, and low p27 expression, may have a potential prognostic importance in recurrent intrathoracic thymomas.
The Journal of thoracic and cardiovascular surgery 08/2009; 138(1):40-5. · 3.41 Impact Factor
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Sara Ramella,
Lucio Trodella,
Tommaso Claudio Mineo, Eugenio Pompeo,
Gerardina Stimato,
Diego Gaudino,
Vincenzo Valentini,
Francesco Cellini,
Marzia Ciresa,
Michele Fiore,
Angelo Piermattei,
Patrizia Russo,
Alfredo Cesario,
Rolando M D'Angelillo
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ABSTRACT: To determine lung dosimetric constraints that correlate with radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional radiation therapy and concurrent chemotherapy.
Between June 2002 and December 2006, 97 patients with locally advanced non-small-cell lung cancer were treated with concomitant radiochemotherapy. All patients underwent complete three-dimensional treatment planning (including dose-volume histograms), and patients were treated only if the percentage of total lung volume exceeding 20 Gy (V(20)) and 30 Gy (V(30)), and mean lung dose (MLD) had not exceeded the constraints of 31%, 18%, and 20 Gy, respectively. The total and ipsilateral lung dose-volume histogram parameters, planning target volume, and total dose delivered were analyzed and correlated with pneumonitis incidence.
If dose constraints to the total lung were respected, the most statistically significant factors predicting pneumonitis were the percentage of ipsilateral lung volume exceeding 20 Gy (V(20)ipsi), percentage of ipsilateral lung volume exceeding 30 Gy (V(30)ipsi), and planning target volume. These parameters divided the patients into low- and high-risk groups: if V(20)ipsi was 52% or lower, the risk of pneumonitis was 9%, and if V(20)ipsi was greater than 52%, the risk of pneumonitis was 46%; if V(30)ipsi was 39% or lower, the risk of pneumonitis was 8%, and if V(30)ipsi was greater than 39%, the risk of pneumonitis was 38%. Actuarial curves of the development of pneumonitis of Grade 2 or higher stratified by V(20)ipsi and V(30)ipsi were created.
The correlation between pneumonitis and dosimetric constraints has been validated. Adding V(20)ipsi and V(30)ipsi to the classical total lung constraints could reduce pulmonary toxicity in concurrent chemoradiation treatment. V(20)ipsi and V(30)ipsi are important if the V(20) to the total lung, V(30) to the total lung, and mean lung dose have not exceeded the constraints of 31%, 18%, and 20 Gy, respectively.
International journal of radiation oncology, biology, physics 08/2009; 76(1):110-5. · 4.59 Impact Factor
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ABSTRACT: Bilateral T2 to T3 thoracoscopic sympathectomy and injection of botulinum toxin-A are presently the most effective modalities in the treatment of primary palmar hyperhidrosis. In this study we evaluated comparative merits of the two therapies.
Patients suffering primary palmar hyperhidrosis were treated by either bilateral T2 to T3 thoracoscopic sympathectomy (n = 68) or by injection of botulinum toxin-A (n = 86). The groups were homogeneous for relevant demographic, physiologic, and clinical data. Quantification of sweat production was performed by Minor's iodine starch and glove tests. Subjective changes were assessed by quality of life questionnaires (Hyperhidrosis, Dermatology Life Quality Index, Short Form-36, Nottingham's Health Profile) and patient's satisfaction self-assessment. A cost comparison between groups was also carried out.
No operative mortality or major morbidity was recorded in either group. Minor's test showed a more significant reduction in the surgical group: +94% versus +63% at 6 months and +94% versus +30% at 12 months. Compensatory sweating was significantly greater and long-lasting in the surgical group. All subjective tests improved rapidly and significantly in both groups. After 6 months, results mildly worsened in the surgical group and more significantly in the botulinum group. Patient's satisfaction was initially greater in the botulinum group (p = 0.03), but after 6 months it significantly reversed (p = 0.04). Surgical treatment cost approximately as much as four botulinum treatments.
Thoracoscopic sympathectomy is superior to botulinum toxin-A injection. The greater initial costs and discomfort are offset by a greater reduction in compensatory sweating.
The Annals of thoracic surgery 08/2009; 88(1):238-45. · 3.74 Impact Factor
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Sara Ramella,
Lucio Trodella,
Tommaso Claudio Mineo, Eugenio Pompeo,
Maria A Gambacorta,
Francesco Cellini,
Marzia Ciresa,
Michele Fiore,
Carlo Greco,
Diego Gaudino,
Gerardina Stimato,
Angelo Piermattei,
Alfredo Cesario,
Rolando M D'Angelillo
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ABSTRACT: The aim of this study is to propose and validate an original new class of solutions for three-dimensional conformal radiation therapy (3DCRT) treatment planning for non-small cell lung cancer (NSCLC) according to the different patterns of disease presentation (on the basis of tumor location and volume) and to explore beams arrangement (planar or no-planar solutions) to respect dose constraints to the lung parenchyma. Benchmarks matched to validate the new approach are interuser reproducibility and saving on planning time. Tumor location was explored and specific categories created according to the tumor volume and location. Therefore, by applying planar and no-planar 3D plans, we searched for an optimization of the beams arrangement for each category. Dose-volume histograms (DVHs) were analyzed and a plan comparison performed. Results were then validated (class solution planning confirmation) by applying the same strategy to another group of patients. This has been realized at two dose levels (50.4 and 59.4 Gy). Fifty-nine patients were enrolled in this dosimetric study. In the first 27 patients ("exploratory sample") three main planning target volume location categories were identified according to the pattern of the disease presentation: (1) centrally located; (2) peripheral T and mediastinal N (P+N); and (3) superior sulcus. Original class solutions were proposed for each location category. On the next 32 patients ("validation sample"), the treatment planning started directly with the recommended approach. Mean V(20 Gy) value was 18.8% (SD +/- 7.25); mean V(30 Gy):12% (SD +/- 4.05); and mean lung dose: 11.6 Gy (SD +/- 5.77). No differences between the two total dose level groups were observed. These results suggest a simple and reproducible tool for treatment planning in NSCLC, allowing interuser reproducibility and cutting down on planning time.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 06/2009; 35(3):169-78. · 1.26 Impact Factor
