Immunological and Inflammatory Impact of Non-Intubated Lung Metastasectomy.

BACKGROUND: We hypothesized that video-assisted thoracic surgery (VATS) lung metastasectomy under non-intubated anesthesia may have a lesser immunological and inflammatory impact than the same procedure under general anesthesia. METHODS: Between December 2005 and October 2015, 55 patients with pulmonary oligometastases (at the first episode) successfully underwent VATS metastasectomy under non-intubated anesthesia. Lymphocytes subpopulation and interleukins 6 and 10 were measured at different intervals and matched with a control group composed of 13 patients with similar clinical features who refused non-intubated surgery. RESULTS: The non-intubated group demonstrated a lesser reduction of natural killer lymphocytes at 7 days from the procedure (p = 0.04) compared to control. Furthermore, the group revealed a lesser spillage of interleukin 6 after 1 (p = 0.03), 7 (p = 0.04), and 14 (p = 0.05) days. There was no mortality in any groups. Major morbidity rate was significantly higher in the general anesthesia group 3 (5%) vs. 3 (23%) (p = 0.04). The median hospital stay was 3.0 vs. 3.7 (p = 0.033) days, the estimated costs with the non-intubated procedure was significantly lower, even excluding the hospital stay. CONCLUSIONS: VATS lung metastasectomy in non-intubated anesthesia had significantly lesser impact on both immunological and inflammatory response compared to traditional procedure in intubated general anesthesia.

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.

Multi-reoperations for lung metastases.

In this study, we investigated role and results of multi-reoperations for lung metastases. From 1986 to 2010, 113 consecutive patients (61 men and 52 women; mean age: 53.2 ± 12.8 years) underwent repeated lung metastasectomy with curative intent in our institution. Two procedures were performed in 113 patients, three in 54, four in 31, five in eight and six in three. There was no perioperative mortality. Cumulative 5-year survival was 65% and this was significantly higher than the value recorded for patients undergoing only one metastasectomy (42%; p = 0.021). Size, number of resections and probability of recurrence increased by number of operation whereas disease free interval reduced. At any metastasectomy both short disease-free interval and multiple metastases resulted in the most significant negative prognosticators. In conclusion, redo metastasectomy is worthwhile for the initial procedures, afterwards both disease-free and overall survivals decrease and surgery lose its efficacy.

Adjuvant chemotherapy for resected early-stage non-small cell lung cancer.

BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations. SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status. MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.

Video-assisted thoracoscopic thymectomy surgery: Tor Vergata experience.

The therapeutic effect of thymectomy on myasthenia gravis is not completely understood. Several types of thymectomy varying in approach and extent have been performed. None of these disclosed a neat superiority over others. Patients desire thymectomy through small, painless, and cosmetically favorable operations. Video-assisted thoracoscopic surgery (VATS) thymectomy fits all these requests as well as that of the surgeon. Indeed, this approach allows for ample operative space, easy maneuverability, and extended thymectomy. No mortality, low morbidity, faster recovery, short hospital stay, and small economical costs are undoubtedly advantages of VATS over transsternal and transcervical thymectomy. In the near future, the introduction of robotic devices will lead to a new era in the surgery of the thymus. Herein we analyzed our comprehensive experience.

Clinical impact of extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: The clinical impact of extrapleural pneumonectomy in malignant pleural mesothelioma is poorly investigated. METHODS: Between 1997 and 2007, 29 consecutive patients underwent extrapleural pneumonectomy for mesothelioma and adjuvant chemoradiotherapy. Function (spirometry, arterial blood gas analysis, 6-min walk test, and echocardiographic fraction ejection estimation), symptoms (quantification of pain, dyspnea, cough, fever, weight loss, and Karnofsky performance status) and quality of life [Medical Outcomes Study Short Form, 36 item (SF-36) and St. George's Respiratory Questionnaire] were timely evaluated. Data were prospectively collected and retrospectively reviewed. RESULTS: Only one postoperative death occurred. 30-day postoperative morbidity was 41%. Median survival was 19.5 months with 17 patients still alive at 1 year and 10 at 2 years, respectively. At 3 months, the expected decrement of forced expiratory volume in 1 s (P = 0.06) and forced vital capacity (P = 0.09) was not significant. Conversely, arterial blood gas, 6-min walk test, cardiac fraction ejection, pain (P < 0.05), dyspnea (P < 0.01), cough (P < 0.05), fever (P < 0.01), weight loss (P < 0.01), performance status (P < 0.01), SF-36 physical (P < 0.01), SF-36 mental (P < 0.05), St. George's Respiratory Questionnaire symptom (P < 0.01), activity (P < 0.05), and impact on mood (P < 0.05) improved. At 12 months, the amelioration of pain, dyspnea, performance status, and physical-related quality of life parameters remained stable. Thereafter, all parameters progressively deteriorated, although pain and dyspnea still persisted above the baseline values even after 24 months in all survivors. Postoperative improvement of pain (P = 0.04), dyspnea (P = 0.04), 6-min walk test (P = 0.03), and SF-36 physical (P = 0.04) and mental (P = 0.03) components were positive prognosticators. CONCLUSIONS: Extrapleural pneumonectomy has a significant and durable impact on function and symptoms as well as on physical and mental components of quality of life in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma: factors influencing the prognosis.

Malignant pleural mesothelioma (MPM) is a highly severe primary tumor of the pleura mainly related to exposure to asbestos fibers. The median survival after symptom onset is less than 12 months. Conventional medical and surgical therapies--either as single lines or combined--are not wholly effective. No universally accepted guidelines have yet been established for patient selection and the use of therapeutic strategies. In addition, retrospective staging systems have proved inadequate at improving therapeutic outcomes. Therapy is currently guided by gross tumor characteristics and patient features; however, these seem less accurate than the biological fingerprint of the tumor. A number of clinical prognostic factors have been considered in large multicenter series and independently validated. A series of novel biomarkers can predict the evolution of the disease. Here we summarize the principal and novel factors that influence prognosis and are thus potentially useful for selecting patients for targeted therapy.

Variations of inflammatory mediators and alpha1-antitrypsin levels after lung volume reduction surgery for emphysema.

RATIONALE: In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia. OBJECTIVES: To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

New predictors of response to neoadjuvant chemotherapy and survival for invasive thymoma: a retrospective analysis.

BACKGROUND: Cell-cycle protein (p27, p21, and p53) expression can predict response to neoadjuvant chemotherapy and prognosis in some neoplasms. This study evaluated whether these markers could also be effective in invasive thymoma during a multimodality treatment. METHODS: Between 1989 and 2008, 33 patients with invasive thymoma underwent surgical resection after neoadjuvant chemotherapy. Expression of p27, p21, and p53 was assessed using immunohistochemistry in specimens retrieved pre and post chemotherapy. Factors influencing response to neoadjuvant chemotherapy and survival were investigated by univariate and multivariate analysis. Good response was defined as complete disappearance of tumor at imaging or necrosis >90% at pathologic studies. RESULTS: Twelve patients disclosed an imaging good response. Complete resection was possible in 17 patients, 9 of whom had presented imaging good response and 11 of whom had revealed pathologic good response. On univariate analysis both imaging and pathologic poor responses were significantly associated with incomplete resection (P = 0.04 and P = 0.03, respectively) and preneoadjuvant triple combination of p27 low, p21 low, and p53 high expressions (P = 0.001 and P < 0.0001, respectively), the last factor being the only one selected on logistic regression (P = 0.01 and P = 0.005, respectively). Long-term survival analysis was negatively influenced by triple combination of p27, p21, and p53 (P < 0.0001) and incomplete resection (P < 0.0001), which were also selected on Cox's regression (P = 0.004 and P = 0.02, respectively). CONCLUSIONS: The triple combination of p27 low, p21 low, and p53 high expressions was the most significant predictor of imaging and pathologic poor responses to neoadjuvant chemotherapy in invasive thymoma. This combination together with incomplete resection was also the most significant negative predictor of long-term survival.

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.

Team Training for Nonintubated Thoracic Surgery.

Nonintubated thoracic surgery arose as supplemental evolution of minimally invasive surgery and is gaining popularity. A proper nonintubated thoracic surgery unit is mandatory and should involve surgeons, anesthesiologists, intensive care physicians, physiotherapists, psychologists, and scrub and ward nurses. Surgical training should involve experienced and young surgeons. It deserves a step-by-step approach and consolidated experience on video-assisted thoracic surgery. Due to difficulty in reproducing lung and diaphragm movements, training with simulation systems may be of scant value; instead, preceptorships and invited proctorships are useful. Preoperatively, patients must be fully informed. Effective intraoperative communication with patients and among the surgical team is pivotal.

Nonintubated Video-Assisted Wedge Resections in Peripheral Lung Cancer.

Wedge resection in peripheral lung cancer is considered a suboptimal procedure. However, in elderly and/or frail patients it is a reliable and safer alternative. This procedure can be easily performed under nonintubated anesthesia, allowing the recruitment of patients considered otherwise marginal for a surgical treatment. Nonintubated anesthesia can reduce lung trauma, operative time, postoperative morbidity, hospital stay, and global expenses. Furthermore, nonintubated anesthesia produces less immunologic impairment and this may affect postoperative oncological long-term results. Wedge lung resection through nonintubated anesthesia can be performed for diagnosis with higher effectiveness given the similar invasiveness of computed tomography-guided biopsy.

Subxiphoid completion thymectomy for refractory non-thymomatous myasthenia gravis.

BACKGROUND: Completion thymectomy may be performed in patients with non-thymomatous refractory myasthenia gravis (MG) to allow a complete and definitive clearance from residual thymic tissue located in the mediastinum or in lower neck. Hereby we present our short- and long-term results of completion thymectomy using subxiphoid video-assisted thoracoscopy. METHODS: Between July 2010 and December 2017, 15 consecutive patients with refractory non-thymomatous myasthenia, 8 women and 7 men with a median age of 44 [interquartile range (IQR) 38.5-53.5] years, underwent video-thoracoscopic completion thymectomy through a subxiphoid approach. RESULTS: Positron emission tomography (PET) showed mildly avid areas [standardized uptake value (SUV) more than or equal to 1.8] in 11 instances. Median operative time was 106 (IQR, 77-141) minutes. No operative deaths nor major morbidity occurred. Mean 1-day postoperative Visual Analogue Scale value was 2.53±0.63. Median hospital stay was 2 (IQR, 1-3.5) days. A significant decrease of the anti-acetylcholine receptor antibodies was observed after 1 month [median percentage changes -67% (IQR, -39% to -83%)]. Median follow-up was 45 (IQR, 21-58) months. At the most recent follow-up complete stable remission was achieved in 5 patients. Another 9 patients had significant improvement in bulbar and limb function, requiring lower doses of corticosteroids and anticholinesterase drugs. Only one patient remained clinically stable albeit drug doses were reduced. One-month postoperative drop of anti-acetylcholine receptor antibodies was significantly correlated with complete stable remission (P=0.002). CONCLUSIONS: This initial experience confirms that removal of ectopic and residual thymus through a subxiphoid approach can reduce anti-acetylcholine receptor antibody titer correlating to good outcome of refractory MG.

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.

Surgical Techniques for Myasthenia Gravis: Video-Assisted Thoracic Surgery.

We describe the various video-assisted thoracic surgery approaches to the thymus currently adopted in nonthymomatous and thymomatous myasthenic patients. Despite several controversies, video-assisted thoracic surgery thymectomy gained worldwide popularity. Classic 3-port approaches proved safe and effective. Uniportal video-assisted thoracic surgery requires consolidated experience, whereas the bilateral approach is considered more extensive. Subxiphoid represents the ultimate and exciting challenge. As an effect of video-assisted thoracic surgery approach, thymectomy is performed earlier; both patients and neurologists are more prone to accept the procedure given the quicker recovery, lesser pain, and better cosmesis. Outcomes are equivalent to those achieved by sternotomy.

Effects of lung volume reduction surgery for emphysema on glycolipidic hormones.

BACKGROUND: Pulmonary emphysema is associated with cachexia and disregulation of the hormones regulating the glycolipid metabolism, insulin resistance, and altered substrate utilization. This study aimed at identifying the effects of lung volume reduction surgery (LVRS) on glycolipidic hormones compared to respiratory rehabilitation (RR). METHODS: Thirty-three patients with moderate-to-severe emphysema who were undergoing video-assisted thoracoscopic LVRS were compared to 31 similar patients who refused the operation and followed a standardized RR program. All patients were evaluated before and 12 months after treatment for respiratory function, body composition, glycolipidic hormones, metabolic parameters, and insulin resistance, which was calculated using the homeostatic model assessment index for insulin resistance (HOMA-IR). These groups were compared to a matched healthy control population. RESULTS: Only after LVRS significant improvements were obtained in respiratory function (FEV1, +25.2%; p<0.0001; residual volume, -19.5%; p<0.0001), metabolic parameters (total cholesterol, +13.1%; p<0.01; high-density lipoprotein cholesterol, +11.2%; p<0.01; triglycerides, +18.4; p<0.001; nonesterified fatty acid, -19.7%; p<0.001), and body composition (fat-free mass [FFM], +6.5%; p<0.01; fat mass [FM], +11.9%; p<0.01). The leptin/FM ratio (-6.1%; p<0.01) and resistin/FM ratio (-5.6%; p<0.01) decreased, whereas the adiponectin/FM ratio (+6.9%; p<0.01) and ghrelin (+9.2%; p<0.01) increased, together with reductions in glycemia (-8.8%; p<0.01), insulin level (-20.4%; p<0.001), and HOMA-IR (-27.2%; p<0.0001). The decrement in residual volume was correlated with increment of FFM (rho=-0.49; p<0.02), FM (rho=-0.55; p<0.009), and ghrelin (rho=-0.52; p<0.01), and also with decreases in leptin corrected for FM (rho=0.50; p<0.02) and, marginally, HOMA-IR (rho=0.35; p=0.07). CONCLUSIONS: After LVRS, glycolipidic hormone levels and nutritional status significantly improved, along with insulin resistance reduction and more physiologic utilization of substrates. Correlations between residual volume and body composition as well as glycolipidic hormone levels suggest that postoperative recovery in respiratory dynamics may induce favorable clinical changes when compared to RR.