1000 cases of tubeless video-assisted thoracic surgery at the Rome Tor Vergata University.

In the early 2000s, the 'Awake Thoracic Surgery Research Group' at Tor Vergata University began a program of thoracic operations in awake nonintubated patients. To our knowledge this was the first program created with this specific purpose. Since then over 1000 tubeless operations have been carried out successfully, making this series one of the widest in the world. Both nononcologic and oncologic conditions were successively approached and major operations for lung cancer are now being performed. Uniportal access was progressively adopted with significant positive outcomes in postoperative recovery, patient acceptance and economical costs. Failure rates due to patient's intolerance and open surgery conversion are progressively reducing. Tubeless thoracic surgery can be accomplished in a safe manner with effective results.

Extended videothoracoscopic thymectomy in nonthymomatous myasthenia gravis.

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.

Awake video-assisted thoracoscopic biopsy in complex anterior mediastinal masses.

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.

Videothoracoscopic approach to the spine in idiopathic scoliosis.

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.

Symptomatic and quality of life changes after extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: Extrapleural pneumonectomy for malignant pleural mesothelioma is considered an aggressive procedure, but symptomatic and quality of life changes are unknown. METHODS: Between 1997 and 2004, 16 consecutive patients underwent extrapleural pneumonectomy for mesothelioma followed by chemo-radiotherapy. Tumor-related symptoms and quality of life (Short-Form-36 and St. George's questionnaires) were assessed pre, 3, 6, 12, and 24 months postoperatively. RESULTS: Thirty-day postoperative major morbidity was 31% with no mortality. At 3 months postoperatively, dyspnea improved in 10 patients (62%), pain in 12 (75%), cough in 10 (62%), fever in 11 (68%), Karnofsky-index in 10 (62%), Short-Form-36 physical-component-summary in 8, mental-component-summary in 5 and total St. George score in 8 (50%). At 1 year 10 (62%) patients were alive and majority of improved parameters were still stable. Thereafter they usually started to decline. Survival was influenced by nonepithelial histology (P < 0.01) and N2-disease (P < 0.01), which showed to be the only prognosticator at Cox regression (P < 0.0001, Odd ratio 5.4). Among symptomatic variables, a 3-month postoperative Short-Form-36 physical-component-summary above the median value correlated significantly with a better prognosis (P < 0.02). CONCLUSIONS: Extrapleural pneumonectomy may rapidly improve symptoms as well as quality of life, especially in physical domains. Other than biological factors, postoperative Short-Form-36 physical component as well, significantly influenced the prognosis.

Awake operative videothoracoscopic pulmonary resections.

The authors' initial experience with awake videothoracoscopic lung resection suggests that these procedures can be easily and safely performed under sole thoracic epidural anesthesia with no mortality and negligible morbidity. One major concern was that operating on a ventilating lung would render surgical maneuvers more difficult because of the lung movements and lack of a sufficient operating space. Instead, the open pneumothorax created after trocar insertion produces a satisfactory lung collapse that does not hamper surgical maneuvers. These results contradict the accepted assumption that the main prerequisite for allowing successful thoracoscopic lung surgery is general anesthesia with one-lung ventilation. No particular training is necessary to accomplish an awake pulmonary resection for teams experienced in thoracoscopic surgery, and conversions to general anesthesia are mainly caused by the presence of extensive fibrous pleural adhesions or the development of intractable panic attacks. Overall, awake pulmonary resection is easily accepted and well tolerated by patients, as confirmed by the high anesthesia satisfaction score, which was better than in nonawake control patients. Nonetheless, thoracic epidural anesthesia has potential complications, including epidural hematoma, spinal cord injury, and phrenic nerve palsy caused by inadvertently high anesthetic level, but these never occurred in the authors' experience. Further concerns relate to patient participation in operating room conversations or risk for development of perioperative panic attacks. However, the authors have found that reassuring the patient during the procedure, explaining step-by-step what is being performed, and even showing the ongoing procedure on the operating video can greatly improve the perioperative wellness and expectations of patients, particularly if the procedure is performed for oncologic diseases. Panic attacks occurred in few patients and could be usually managed through moderately increasing the depth of sedation while maintaining spontaneous breathing. Finally, as long as the physiologic impact of awake metastasectomy is definitively elucidated, the authors believe this modality should be used for unilateral procedures, while deserving a staged bilateral approach for bilateral lung metastasectomy. Avoidance of general anesthesia results in a faster recovery with immediate return to many daily life activities, including drinking, eating, and walking, and a reduction in hospital stay and procedure-related costs. If confirmed with future studies, these results could advocate earlier resection of peripheral solitary pulmonary nodules, reducing the risk for delaying a diagnosis of unexpected pulmonary malignancy. Furthermore, potential new frontiers of awake thoracoscopic surgery might include assessment of feasibility and safety of anatomic resections in properly selected instances. Ethical and economical concerns push remorselessly for less frequent and less-invasive surgery. Administrators advocate minimal hospitalization and cost-saving treatments, whereas patients ultimately ask for appropriate health care. Thoracic surgeons of the third millennium must accept the challenge of this dynamic and rapidly evolving scenario without loosing the right root, which probably lays just between well-established conventional surgery techniques and newly available advanced technology tools. Awake thoracic surgery will benefit from evidence-based data that are progressively accumulating. Findings will stimulate experts to continue an active clinical investigation in this unpredictably evolving surgical field, which might ultimately lead to a better understanding of cardiorespiratory physiology and effects of the surgical pneumothorax and thoracic epidural anesthesia on perioperative, respiratory function in awake patients. As the Italian architect Renzo Piano recently stated, "Recovering in the past can be reassuring but the future is the only place where we can go."

Immunohistochemistry-detected microscopic tumor spread affects outcome in en-bloc resection for T3-chest wall lung cancer.

OBJECTIVE: This study is aimed at analyzing the effect of immunohistochemistry-detected microscopic tumor spread on long-term survival after en-bloc lung and chest wall resection for T3-chest wall non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 47 patients (mean age 64.4+/-7.1 years, range 48-77) who underwent radical en-bloc lung and chest wall resection for NSCLC between 1987 and 2000. Resection margins, invasion depth, and lymph nodes were re-assessed by immunohistochemistry with AE1/AE3 anti-cytokeratin and anti-CEA monoclonal antibodies. RESULTS: Operative mortality and morbidity were 2.1% and 34%, respectively. At immunohistochemistry analysis, five patients (10.6%) revealed microinfiltration of the resection margins that was significantly correlated with the development of local recurrence (p<0.005). Nodal micrometastases were found in 4 out of 33 N0 patients (12.1%), and correlated with distant relapse (p<0.001). Overall and disease-free survivals were significantly influenced by N-status (p<0.001), especially after re-evaluation of micrometastases (p<0.0001), and resection margins microinfiltration (p<0.0001) being these last two the only significant prognostic factors at Cox regression analysis. Five-year overall survival in radically resected patients was 73%. CONCLUSIONS: In this study immunohistochemical analysis allowed to identify patients at higher risk of recurrence following en-bloc resection for T3-chest wall NSCLC.

Detection and expression of human papillomavirus oncogenes in non-small cell lung cancer.

Human papillomavirus (HPV) has been found in lung cancer cases with variable frequency. In the present study, we analysed a series of 38 patients with non-small cell lung cancer (NSCLC) (21 paraffin-embedded archival samples and 17 fresh surgical specimens) for the presence of E6 and E7 oncogenes of HPV16, 18 and 31. Eight of the tumours were positive (21%): six HPV16, one HPV16+18, and one HPV31. The normal tissue surrounding the HPV-positive tumour was negative for the presence of the virus. Sequencing analysis of URR, of HPV16, which was the most frequently found HPV type in our cases, showed an adenosine deletion at nucleotide 7861 (E2-binding site) in four out of six patients. Sequencing of the entire E6 and E7 genes of HPV16 showed a T to G transition at nucleotide position 350 of E6, in all examined cases. This mutation is associated to the European variant of HPV16. Analysis of E6 and E7 transcripts was performed on the six fresh surgical specimens infected by HPV16. Our study showed that all of the tumours investigated, except one, contained E6 and E7 transcripts. Only in one case could we identify an unspliced form of the E6 transcript. Our results strengthen the relationship between HPV and NSCLC and support the hypothesis that HPV infection could play a role in bronchial carcinogenesis.

Results of unilateral lung volume reduction surgery in patients with distinct heterogeneity of emphysema between lungs.

OBJECTIVE: This study was undertaken to analyze the comprehensive outcome of unilateral lung volume reduction in patients with distinct heterogeneity of emphysema between lungs assessed by a visual radiologic scoring system. METHODS: Ninety-seven patients who underwent intentional unilateral lung volume reduction because of distinct heterogeneity of emphysema between lungs (asymmetric ratio of emphysema >/=1.1) between 1995 and 2003 were evaluated. Baseline median measures were 0.83 L for forced expiratory volume in 1 second, 5.0 L for residual volume, 380 m for 6-minute walking test distance, 0.50 for maximal incremental treadmill test score, and 25 for physical functioning domain score assessed by the Short Form-36 Quality of Life questionnaire. RESULTS: Median follow-up was 34 months. Significant improvements occurred for as long as 36 months in forced expiratory volume in 1 second (+24%), residual volume (-12%), Short Form-36 Quality of Life questionnaire physical functioning domain score (+100%), 6-minute walking test distance (+18%), and maximal incremental treadmill test score (+200%). A direct correlation was found between asymmetric ratio of emphysema and change in forced expiratory volume in 1 second ( r = 0.65, P < .00001). At 60 months, residual volume (-6.2%), maximal incremental treadmill test score (+100%), and Short Form-36 Quality of Life questionnaire physical functioning domain score (+70%) were still significantly improved. Five-year survival was 82%; 5-year freedom from contralateral lung volume reduction was 70%. CONCLUSIONS: In this series, significant, long-lasting improvements and satisfactory survival were seen after intentional unilateral lung volume reduction. Heterogeneity of emphysema between lungs was directly correlated with improvement at 36 months in forced expiratory volume in 1 second. Our results suggest that unilateral lung volume reduction is a suitable option for patients with distinct heterogeneity of emphysema between lungs.

Plasma von Willebrand factor antigen levels in non-small cell lung cancer patients.

BACKGROUND: To analyze the behavior of circulating von Willebrand factor antigen (vWf:Ag) in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Pre-surgical vWf:Ag levels were measured in 64 patients with histologically diagnosed NSCLC compared to 64 patients with benign pulmonary diseases, as well as 64 age- and sex-matched controls. RESULTS: Patients with NSCLC had mean vWf:Ag concentrations lower than either controls or benign patients (p =0.001). CEA was the only variable predictive of low vWf:Ag levels (p<0.01). Five of the 64 NSCLC patients had abnormally low vWf:Ag concentrations (<36 IU/dL). When these patients were excluded from the analysis, the vWf:Ag levels of NSCLC patients did not differ from those of controls (p=0.19). CONCLUSION: The vWf antigen levels of NSCLC patients are not substantially altered. A small subset of these patients will have a depletion of circulating vWf:Ag, probably because of a paraneoplastic process associated with an advanced stage of disease.

Soluble CD40 ligand plasma levels in lung cancer.

PURPOSE: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.

An update on myasthenia gravis, challenging disease for the dental profession.

Myasthenia gravis is an autoimmune neuromuscular disorder characterized by fluctuating weakness and skeletal muscle fatigue. Clinical signs and symptoms may vary considerably according to the age at presentation, patterns of autoantibodies and associated thymic abnormalities, so that therapeutic options are highly individualized. Facial and oropharyngeal muscle weakness is common at disease onset, and therefore dentists are often the first health professionals to encounter these patients. Myasthenic patients require special consideration and advice in order to ensure optimal and safe dental treatment. Oral manifestations, treatment timing and modality, the choice and effects of drugs and medications, and prevention of myasthenic crisis are all important aspects with which dentists and oral health care providers should be thoroughly acquainted.

Vascular endothelial growth factor (VEGF-A) plasma levels in non-small cell lung cancer: relationship with coagulation and platelet activation markers.

Platelet activation, commonly found in lung cancer patients, may cause the release of angiogenic factors, such as vascular endothelial growth factor (VEGF-A). The present study was designed to investigate whether plasma VEGF-A levels were associated to different stages of non-small cell lung cancer (NSCLC). Moreover, sP-selectin, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TATc) and D-dimer levels were measured to test the hypothesis of an involvement of platelet and coagulation activation in tumor angiogenesis. VEGF-A, sP-selectin, F1+2, TATc and D-dimer levels were elevated in 65 patients with NSCLC, particularly in metastatic patients. sP-selectin (p <0.003) and F1+2 (p <0.005) levels were independently associated to VEGF-A. In addition, patients with positive levels of both sP-selectin and F1+2 had the highest levels of VEGF-A. In conclusion, our findings support the hypothesis that thrombin generation might induce platelet activation and VEGF-A release in NSCLC.

Quality of life after tailored combined surgery for stage I non-small-cell lung cancer and severe emphysema.

BACKGROUND: We analyzed the early and long-term quality of life changes occurring in 16 patients undergoing tailored combined surgery for stage I non-small-cell lung cancer (NSCLC) and severe emphysema. METHODS: Mean age was 65 +/- 5 years. All patients had severe emphysema with severely impaired respiratory function and quality of life. Tumor resection was performed with sole lung volume reduction (LVR) in 5 patients, separate wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 6 patients. A bilateral LVR was performed in 5 patients. Quality of life was assessed at baseline and every 6 months postoperatively by the Short-form 36 (SF-36) item questionnaire. RESULTS: Mean follow-up was 44 +/- 21 months. All tumors were pathologic stage I. There was no hospital mortality nor major morbidity. Significant improvements occurred for up to 36 months in the general health (p = 0.02) domain and for up to 24 months in physical functioning (p = 0.02), role physical (p = 0.005), and general health (p = 0.01) SF-36 domains. Associated improvements regarded dyspnea index (-1.3 +/- 0.6) forced expiratory volume in one second (+0.28 +/- 0.2L), residual volume (-1.18 +/- 0.5L) and 6-minute-walking test distance (+86 +/- 67 m). Actuarial 5-year survival was similar to that of patients with no cancer undergoing LVRS during the same period (68% vs 82%, p = not significant). CONCLUSIONS: Our study suggests that selected patients with stage I NSCLC and severe emphysema may significantly benefit from tailored combined surgery in terms of long-term quality of life and survival.

From "awake" to "monitored anesthesia care" thoracic surgery: A 15 year evolution.

Although general anesthesia still represents the standard when performing thoracic surgery, the interest toward alternative methods is increasing. These have evolved from the employ of just local or regional analgesia techniques in completely alert patients (awake thoracic surgery), to more complex protocols entailing conscious sedation and spontaneous ventilation. The main rationale of these methods is to prevent serious complications related to general anesthesia and selective ventilation, such as tracheobronchial injury, acute lung injury, and cardiovascular events. Trends toward shorter hospitalization and reduced overall costs have also been indicated in preliminary reports. Monitored anesthesia care in thoracic surgery can be successfully employed to manage diverse oncologic conditions, such as malignant pleural effusion, peripheral lung nodules, and mediastinal tumors. Main non-oncologic indications include pneumothorax, emphysema, pleural infections, and interstitial lung disease. Furthermore, as the familiarity with this surgical practice has increased, major operations are now being performed this way. Despite the absence of randomized controlled trials, there is preliminary evidence that monitored anesthesia care protocols in thoracic surgery may be beneficial in high-risk patients, with non-inferior efficacy when compared to standard operations under general anesthesia. Monitored anesthesia care in thoracic surgery should enter the armamentarium of modern thoracic surgeons, and adequate training should be scheduled in accredited residency programs.

Randomized comparison of awake nonresectional versus nonawake resectional lung volume reduction surgery.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

Awake thoracoscopic bullaplasty.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.