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Purpose: The objective of the study was to highlight sources of harm that could negatively affect the lung cancer multidisciplinary team (MDT) activities to reduce the level of risk of each factor., Methods: A modified Delphi approach was used by a board of multi-health care professionals of the lung cancer MDT to identify the main processes, subprocesses, and risk factors of the multidisciplinary pathway of patients with lung cancer. A semiquantitative matrix was built with a five-point scale for probability of harm (likelihood) and severity of harm (consequences) according to the international risk management standards (ISO 31000-2018). The risk level was calculated by multiplying likelihood × consequences. Mitigation strategies have been identified and applied by the MDT to reduce risks to acceptable levels., Results: Three main processes (outpatient specialist visit, MDT discussion, and MDT program implementation), eight related subprocesses, and 16 risk factors were identified. Four risk factors (25%) were related to outpatient specialist visit, seven (43.75%) to case discussion, and five (31.25%) to program implementation. Overall, two risk factors were assigned a low-risk level (12.5%), 11 a moderate-risk level (68.75%), one (6.25%) a high-risk level, and two (12.5%) a very high-risk level. After the implementation of mitigation measures, the new semiquantitative risk analysis showed a reduction in almost all hazardous situations: two risk factors (12.5%) were given a very low level, six (37.5%) a low level, seven (43.75%) a moderate level, and one (6.25%) a very high level., Conclusion: An interdisciplinary risk assessment analysis is applicable to MDT activities by using an ad hoc risk matrix: if the hazard is identified and monitored, the risk could be reduced and managed in a short time.

Background: Invasiveness is considered one of the cornerstones of every field of surgery, and video-assisted thoracoscopic (VATS) approaches are now routinely used worldwide to perform pulmonary resections. Recently, robotic-assisted thoracic surgery (RATS) has become the preferred technique in many centers; it is routinely performed using three or four ports with at least one service incision, contrasting with the real concept of invasiveness, especially when compared to uniportal VATS (U-VATS). Hereby, we present our early experience with uniportal RATS (U-RATS) pulmonary resections for early-stage lung cancer. Technical details of surgical steps are accurately described and commented on., Results: Twenty-four consecutive patients with lung cancer underwent U-RATS anatomical pulmonary resections at our institute. All procedures were completed with the uniportal approach. The mean operative time was 210 min (range 120-350); in the last 10 cases, the operative time was significantly reduced (180 min) compared to the first 10 cases (232 min) ( p  < 0.02), showing a very fast learning curve. The postoperative pain score was comparable to that for U-VATS and was constantly low., Conclusions: U-RATS is a safe and feasible technique, combining the advantages of U-VATS with the well-known advantages of robotic surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Mercadante, Martucci, De Luca, La Rocca and La Manna.)

Few treatment options are available for patients with small cell lung cancer (SCLC) in progression after a first-line therapy. A novel therapeutic approach is represented by lurbinectedin, a synthetic derivative of trabectedin that works by inhibiting oncogenic transcription and promoting apoptosis in tumor cells. A phase II basket trial demonstrated the activity of lurbinectedin at the dose of 3.2 mg/m 2 in patients with SCLC who had failed a previous chemotherapy, with a response rate of 35.2%, a median progression-free survival (mPFS) of 3.5 months, and a median overall survival (mOS) of 9.3 months. Common severe adverse events (grades 3-4) were hematological disorders, including anemia (9%), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). On the basis of the positive results of this phase II study, on June 2020, lurbinectedin was approved by the Food and Drug Administration as second line for SCLC patients in progression on or after platinum-based therapy. The subsequent phase III trial comparing the combination of lurbinectedin plus doxorubicin vs. CAV (cyclophosphamide, Adriamycin, and vincristine) or topotecan did not demonstrate an improvement in overall survival, although the experimental arm showed a superior safety profile. Combinations of lurbinectedin with other drugs, cytotoxic agents and immune checkpoint inhibitors, are currently under investigation. The results of these studies should better define the optimal clinical application of lurbinectedin., Competing Interests: AlM declares the following conflicts of interest: Speaker’s fee or advisory board: MSD, BMS, Boehringer, Pfizer, Roche, AstraZeneca, Novartis, Takeda, Eli-Lilly. NN declares the following personal financial interests (speaker’s fee and/or advisory boards): MSD, Qiagen, Bayer, Biocartis, Incyte, Roche, BMS, MERCK, Thermofisher, Boehringer Ingelheim, Astrazeneca, Sanofi, Eli Lilly; Institutional financial interests (financial support to research projets):MERCK, Sysmex, Thermofisher, QIAGEN, Roche, Astrazeneca, Biocartis. Non-financial interests:President, International Quality Network for Pathology (IQN Path); President, Italian Cancer Society (SIC). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Manzo, Sforza, Carillio, Palumbo, Montanino, Sandomenico, Costanzo, Esposito, Laudato, Mercadante, La Manna, Muto, Totaro, De Cecio, Picone, Piccirillo, Pascarella, Normanno and Morabito.)

RET rearrangements are observed in 1-2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

Inhibition of angiogenesis has been demonstrated to be an efficacious strategy in treating several tumors. Vascular endothelial growth factor (VEGF) is the most important protein with proangiogenic functions and it is overexpressed in small cell lung cancer (SCLC). Bevacizumab, a monoclonal antibody directed against VEGF, showed a promising activity in combination with etoposide and cisplatin as first-line treatment of patients with extended stage (ES)-SCLC and two randomized studies confirmed that bevacizumab improved PFS, but failed to prolong OS. Instead, disappointing results have been observed with endostar, sunitinib, sorafenib, vandetanib, and thalidomide in combination with chemotherapy in the first-line setting, with sunitinib in the maintenance setting, with sunitinib, cediranib and nintedanib as single agents or ziv-aflibercept in combination with topotecan in second-line setting. Only anlotinib improved OS and PFS as third-line therapy in Chinese patients with SCLC, and it was approved with this indication in China. Future challenges are the evaluation of the role of angiogenesis inhibitors in combination with immune- checkpoint inhibitors and chemotherapy in SCLC patients and the identification of predictive biomarkers of response to both agents., Competing Interests: AMor declares the following conflicts of interest: Speaker’s fee: MSD, BMS, Boehringer, Pfizer, Roche, AstraZeneca; Advisory Board: Takeda. NN declares the following personal financial interests (speaker’s fee and/or advisory boards): MSD, Qiagen, Bayer, Biocartis, Incyte, Roche, BMS, MERCK, Thermofisher, Boehringer Ingelheim, Astrazeneca, Sanofi, Eli Lilly; Institutional financial interests (financial support to research projects): MERCK, Sysmex, Thermofisher, QIAGEN, Roche, Astrazeneca, Biocartis. Non-financial interests: President, International Quality Network for Pathology (IQN Path); President, Italian Cancer Society (SIC). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Montanino, Manzo, Carillio, Palumbo, Esposito, Sforza, Costanzo, Sandomenico, Botti, Piccirillo, Cascetta, Pascarella, La Manna, Normanno and Morabito.)

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36-63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents.

Introduction: Atezolizumab is a humanized monoclonal antibody against PD-L1 capable of enhancing antitumor immune activity, with a demonstrated activity as single agent in patients with advanced non-small-cell lung cancer (NSCLC)., Areas Covered: This review summarizes the clinical data emerging from randomized clinical studies with atezolizumab in NSCLC and small-cell lung cancer (SCLC), focusing in particular on the efficacy and safety data regarding the combinations of atezolizumab plus chemotherapy in the IMpower studies., Expert Opinion: A significant improvement in progression-free survival and in overall survival was observed in IMpower 130 and 150 (NSCLC non-squamous) and 133 (SCLC), with an acceptable safety profile. In particular, the most common immune-related adverse events were rash (18-28% of patients), hypothyroidism (8-15%), hepatitis (5-17%), pneumonitis (2-7%), and colitis (1.5-2.3%). The safety profile of atezolizumab in combination with chemotherapy was consistent with the known adverse events related to single-agent atezolizumab and no new adverse events were observed. Ongoing studies will evaluate the role of atezolizumab in other settings (adjuvant and neoadjuvant) and in combination with chemotherapy and radiotherapy for patients with locally advanced NSCLC and the role of predictive factors (B-FAST study).

Immune checkpoint inhibitors against programmed cell death protein 1/programmed death-ligand 1 (PD-L1) have proven to be remarkably effective in non-small cell lung cancer. PD-L1 represents a predictive biomarker in lung cancer, although its heterogenous expression represents an emerging challenge for accurate biomarker-based patient selection. Lung adenocarcinomas (ADCs) show a high rate of intratumor morphologic heterogeneity that may reflect a heterogenous molecular and immunophenotypic profile. The aim of our study was to analyze the expression of PD-L1 in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas (mADCs) and adenosquamous lung carcinomas (AdSqLCs). As many as 73 mADCs and 6 AdSqLCs were selected. Comprehensive histologic subtyping was performed, and PD-L1 expression was assessed by immunohistochemistry assay using different primary antibodies and automated immunostainers. Overall, PD-L1 expression was observed in 37 of 79 cases (39.2%) (31 mADCs and all AdSqLCs). PD-L1 expression was heterogenous in 22 of 37 PD-L1-positive cases (23.2% mADC and 83% AdSqLC). PD-L1 expression was observed more frequently in ADC with solid pattern. Heterogeneity of PD-L1 expression was significantly related to the presence of micropapillary (P=0.028) and solid (P=0.017) patterns. All PD-L1-positive cases were epidermal growth factor receptor wild-type, 2 cases harbored concomitantly PD-L1 expression and ALK rearrangement. Our data suggest that PD-L1 expression is quite heterogenous in mADCs and AdSqLCs, partly contributing to explaining the discrepant results between biopsy and surgical resections and discordant clinical effectiveness in regard to PD-L1-positive or negative ADC diagnosed on cytology/small biopsy.

Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion for angiogenesis inhibitors, the increased incidence of treatment associated adverse events, the exclusion of patients with tumors located in central position or at risk of hemorrhage. The identification of predictive biomarkers is an important goal of research to optimize the combined use of these agents., Competing Interests: AM declares the following speakers’ bureau: Roche, Takeda, Pfizer, Boehringer Ingelheim, AstraZeneca, MSD Oncology, BMS. The other authors declare that no conflicts of interest., (© The Author(s) 2020.)

Aim: Terra dei Fuochi (TdF), the so-called 'Land of Fires' in Southern Italy, is an agricultural territory characterized by illegal dumping of toxic waste known to occur since the 1980s. It is unknown whether prognosis of patients developing cancer and living in that area may differ compared to those living in areas not exposed to this specific type of pollution. We retrospectively analyzed the 5-year survival rates of patients originating from the TdF diagnosed with lung cancer compared to patients from other areas., Materials and Methods: Patients consecutively operated on for non-small cell lung cancer (NSCLC) between November 2004 and April 2013 at the Division of Thoracic Surgery of the National Cancer Institute of Naples were eligible. The study outcome was overall survival (OS). In addition, the TdF and non-TdF groups were compared through propensity score matching (PSM)., Results: Overall, 439 patients with resectable NSCLC were operated on, 123 (28%) from the TdF and 316 (72%) from other referral centers of our catchment area. There were 301 males and 138 females; the median age of the entire surgical population was 65 years (range=25-83) years. Apart from a different prevalence of hypertension and underweight patients, preoperative factors were evenly distributed between the two groups. At univariate analysis, OS was not different between the TdF and non TdF group (median 72 and 68 months, respectively; p=0.75 log-rank test). Multivariable analysis confirmed that living in the TdF area had no prognostic impact (hazard ratio=1.05; 95% confidence interval=0.70-1.57; p=0.78) on OS. PSM confirmed no statistically significant difference of OS (hazard ratio=1.01, 95% confidence interval=0.67-1.52; p=0.93)., Conclusion: Following surgery for lung cancer, TdF and non-TdF surgical candidates had similar long-term survival. Originating from the TdF does not seem to be associated with worse outcomes after surgical treatment of patients with lung cancer., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Extensive primary resections or redos may produce significant chest wall defects requiring creative reconstructions in order to avoid reduction of the intrathoracic volume. We describe the successful use of an innovative technique for chest wall reconstruction based on the concept of roof coverage of sport arenas. In fact, titanium plates are anchored to the residual rib stumps along the parasternal and paravertebral lines. The acellular collagen matrix prosthesis was sutured to the free edges of the same titanium plates to create a roof, reproducing the chest wall dome geometric configuration. A 36-year-old female patient was diagnosed with an extensive desmoid tumor involving the lateral segments of second to fifth ribs on the right side. The arena roof technique allowed for adequate expansion of the uninvolved lung and optimal chest wall functional recovery., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The use of bipolar sealing devices during pulmonary resection is particularly useful in thoracoscopic surgery. Theoretically, a bipolar device, which contains the current in a smaller area and completes the current cycle only through the tissue between the electrodes, may reduce the proportion of patients experiencing atrial fibrillation compared with monopolar devices such as the electrosurgical pencil using which the current completes the cycle through the patient. We investigated the impact of the LigaSure™ (LS) tissue fusion technology with the ForceTriad™ energy platform device on the incidence of postoperative atrial fibrillation and on the reduction of postoperative chest tube output and hospital length of stay after open pulmonary lobectomy., Methods: A pilot prospective randomized, controlled trial comparing LS tissue fusion technology with the ForceTriad™ energy platform to the conventional electrosurgical pencil. Overall, 146 patients with resectable lung cancer were recruited at the Division of Thoracic Surgery of the Istituto Nazionale Tumori, Fondazione Pascale, IRCCS, between January 2011 and July 2013. Of these, 119 candidates to open lobectomy for non-small-cell lung cancer were randomized to either LS tissue fusion technology with the ForceTriad™ energy platform (LS: 57 patients) or standard haemostatic procedure (standard treatment, ST: 62 patients) for hilar and mediastinal nodal dissection. The primary end-point was to compare the incidence of postoperative atrial fibrillation of LS compared with ST. The secondary end-point was to compare the efficacy of LS compared with ST in terms of total chest tube drainage, daily chest tube drainage and chest tube duration., Results: There was no statistically significant difference between LS and ST in terms of postoperative atrial fibrillation (P=0.31). However, LS was associated to significant reduction of duration of both mediastinal nodal dissection (P=0.017) and the cumulative chest tube drainage (P=0.025)., Conclusions: The incidence of atrial fibrillation with LS tissue fusion technology with the ForceTriad™ energy platform is not reduced as compared with conventional electrosurgical pencil. However, the use of LS during mediastinal nodal dissection is associated to shorter duration of lymphadenectomy and duration of chest tube drainage., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: New materials (NM) such as titanium plates, cryopreserved grafts, and acellular collagen matrices are being increasingly used for chest wall reconstruction as a result of improved incorporation while maintaining structural stability and reduced need for removal from infected areas. Direct comparisons between NM and conventional materials (CM) in terms of local morbidity and need for prosthesis removal are lacking., Methods: Between January 2005 and July 2013, 109 procedures were performed to remove chest wall tumors in 86 patients. Of these, 32 underwent complex chest wall reconstructions owing to either recurrence, defect extension (greater than 3 ribs or >100 cm2) or local conditions (ie, previous irradiation or infection). New materials and CM (ie, polytetrafluoroethylene and methyl methacrylate) were used in 17 (53%) and 15 (47%) patients, respectively. Of the 32 patients included in the high complexity group, 23 patients did not exhibit any postoperative complications (72%). However, 9 patients (28%) underwent both a first and a second reoperation after a median interval of 4 months from the first procedure (range, 7 days to 60 months). Vacuum-assisted closure (VAC) was instituted in all patients as a means to control sepsis and facilitate space obliteration with healthy tissue., Results: In 7 patients the reason for reintervention was local wound complications. In 4 of 7 patients, the prosthesis had to be removed (3 CM and 1 NM, 4.6% of the whole series; 12.5% in the high complexity group, 5.9% for NM and 20% for CM). The median time to complete chest wall healing after VAC in patients with local sepsis was 14 months (range, 5 to 60 months). All patients are currently alive and well except for 1 who died 11 months after complete chest wall healing as a result of dissemination of metastatic chondrosarcoma. At univariate analysis, predictors of overall and grade 2 or less morbidity according to the Common Terminology Criteria for Adverse Events version 4.0 were first (p=0.038) and second (p=0.015) redo operations. Conversely, patients with a body mass index of less than 25 kg/m2 (p=0.049) undergoing one (p=0.032) or two reconstructions (p=0.00047) with combined materials (p=0.00029) were more likely to experience local wound complications and require VAC. On multiple regression analysis, redo operations (first, p=0.032; second, p=0.00047) and the use of combined (synthetic and biologic) materials (p=0.0029) were confirmed to be related to an increased incidence of wound complications., Conclusions: Multiple redo operations after complex chest wall reconstruction performed with a combination of NM and CM may be associated with an increased incidence of local wound complications. Nevertheless, in these cases, the use of NM and VAC yielded a low rate (5.8% versus 20% with CM) of prosthesis removal while achieving complete wound healing., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Uniportal video-assisted thoracic surgery (VATS) technique has been described both for diagnostic and therapeutic indications. Outcomes after uniportal VATS have never been reported in large series., Methods: Between January 2000 and December 2010, 644 uniportal VATS procedures (334 male and 310 female patients; median age, 55.5 years; range, 16 to 85) were performed by a single surgeon. This figure represents 27.7% of all the thoracic surgical procedures in the study period (2,369). Of the 644 uniportal VATS, 329 (51.1%) were diagnostic procedures for pleural conditions. Of the remaining 315 uniportal VATS procedures, 14 (2.2%) were performed for pre-thoracotomy exploration for lung cancer, and 115 (17.8%) for miscellaneous conditions including diagnosis of mediastinal masses. In addition, 186 nonanatomic wedge resections (28.9% of the total uniportal VATS procedures) were performed for pulmonary conditions; of these, 146 were done for pulmonary nodules., Results: Median operative time was 18 and 22 minutes for uniportal VATS for diagnostic non-pulmonary indications and for wedge resections, respectively. Out of 644 patients, conversion to either 2 or 3 port VATS or minithoracotomy was necessary in 3.7% of the patients, often due to incomplete lung collapse (92%). Inclusive of the day of insertion, the chest drain was removed after a median of 4.3 (range, 2 to 20) and 2.4 days (range, 0 to 6) after uniportal VATS for pleural effusions and uniportal VATS lung wedge resections, respectively. Mortality and major morbidity after uniportal VATS was 0.6% and 2.8%, respectively. All deaths reported after uniportal VATS were for pleural effusions. Inclusive of the operative day, median hospitalization after surgery for uniportal VATS for pleural effusions and for wedge resections were 5.3 and 3.4 days, respectively., Conclusions: In our experience, uniportal VATS was performed in one third of our surgical candidates with limited operative time, a very low conversion rate to conventional VATS or minithoracotomy, a very low morbidity and mortality, and, short hospitalization. Uniportal VATS is an underappreciated procedure that can be reliably used in the diagnostic pathways of several intrathoracic conditions and to resect small pulmonary nodules with either diagnostic or therapeutic purposes. As such, uniportal VATS represents a consolidated addition to the surgical armamentarium., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Maximal oxygen consumption (VO(2)max) is considered a decisive test for risk prediction in patients with borderline cardiopulmonary reserve. Guidelines have adopted decreasing VO(2)max cut-off values to define operability within acceptable mortality and morbidity limits. We wanted to investigate how the adoption of decreasing VO(2)max cut-off-values assessment contributed to better select lung surgery candidates., Methods: One hundred and nineteen consecutive surgical candidates have been prospectively analyzed as a sample population. Preoperative work-up included spirometry and transfer factor (DLco); irrespective of the spirometric values, these patients were subjected to VO(2)max assessment. Surgical eligibility was decided by the same surgeon throughout the series. In the postoperative period, overall mortality and the occurrence of any, major or minor complications was recorded and graded according to the Common Terminology Criteria for Adverse Events v.4.3., Results: Three arbitrary cut-offs were introduced at 15, 14 and 12 mL(.)kg(-1) (.)min(-1). Notably, 15 and 12 mL(.)kg(-1) (.)min(-1) correlated with percentage VO(2)max values of 50% and 35% of predicted (P<0.0001 and 0.0079), respectively. Accordingly, the patients were subdivided into groups in which the prevalence of postoperative morbidity was recorded. The groups were homogeneous as to age, BMI, preoperative absolute and percentage FEV1 and DLco. In the Cox proportionate-hazards multivariate analysis, VO(2)max less than 35% (P=0.0017) and CTCAE >2 (P=0.0457) emerged as significant predictors of survival after surgery. Conversely on logistic regression analysis, age over 70 years (P=0.03) and pneumonectomy (P=0.001), but not VO(2)max cut-off values, were significant predictors of major (CTCAE >2) morbidity., Conclusions: Since VO(2)max is increasingly used to contribute to risk prediction for the individual patient, surgeons need to be advised that the concept of a definitive, generalized cut-off value for VO(2)max is probably a contradiction in terms. Patient-specific VO(2)max values are more likely to contribute to risk assessment since they may reflect the primarily affected component among the determinants of maximal oxygen consumption. Whether patient-specific VO(2)max should be routinely used by surgeons to define operability for borderline patients needs further evaluation.

Objectives: Flexible bronchoscopy is recommended to confirm correct placement of double-lumen tubes used for thoracic anesthesia. However, there is still controversy over routine bronchoscopic confirmation of their position. This study aimed to verify the usefulness of flexible bronchoscopy for confirming the position of double-lumen tubes after blind intubation., Methods: During a 9-month period, consecutive patients undergoing elective oncologic thoracic surgery were prospectively enrolled in the study. All patients were intubated with a left disposable polyvinyl chloride double-lumen tube. Immediately after intubation, clinical verification was made by the anesthesiologist. Then, the endoscopist performed flexible bronchoscopy with a 2.8-mm diameter Olympus(®) video bronchoscope, and verified the position of the double-lumen tube, before positioning the patient. The double-lumen tube was in optimal position, if the bronchial cuff was immediately below the tracheal carina, and there was a clear view of the left subcarina, with unobstructed left upper and lower bronchi. Misplacement of the double-lumen tube was diagnosed when the tube had to be moved (in or out) for more than 0.5 cm to correct its position. Critical malposition meant a double-lumen tube dislocated in the trachea or in the right bronchi, requiring immediate re-intubation under bronchoscopic guidance., Results: A total of 144 patients (44 women (42%) and 60 men (58%), with a mean age of 51 years (range 25-77 years)) were enrolled in the study. Surgical procedures included 37 right-sided and 31 left-sided thoracotomies, 22 video-assisted thoracoscopic surgeries (VATSs) (16 right-sided and six left-sided), one median sternotomy, six mediastinotomies, and seven miscellaneous procedures. In 66 (63%, 95% confidence interval 53.2-71.8%) cases, there was complete agreement between the anesthesiologist and the endoscopist. The latter diagnosed misplacement of the double-lumen tube in 33 (32%, 95% confidence interval 22.8-40.7%) patients and critical malposition in five (5%, 95% confidence interval 0.7-8.9%) cases., Conclusions: After blind intubation, 37% of double-lumen tubes required repositioning by means of flexible bronchoscopy, despite positive evaluation made by the anesthesiologist. Our data suggests that initial bronchoscopic assessment should be made with the patient still in the supine position, and confirms that flexible bronchoscopy is useful in verifying the correct position of double-lumen tubes or adjusting possible misplacements, before starting thoracic surgery., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Purpose: An intrinsic limitation of video-assisted thoracic surgery (VATS) resides in the impossibility to palpate the lung to identify embedded nodules. We wanted to investigate the use of intraoperative ultrasonography to detect pulmonary nodules during uniportal VATS., Description: We describe our initial experience with the identification of peripheral pulmonary nodules with an articulating ultrasound probe introduced through a single VATS incision. The instrument was used in 2 patients with solitary pulmonary nodules and previous history of extrathoracic cancer., Evaluation: The lung nodules were identified by the articulating probe and resected on wide tumor-free margins through uniportal VATS. Subsequent lung palpation through minithoracotomy confirmed the absence of additional lesions., Conclusions: Intraoperative ultrasound scanning of the lung with an articulating probe can be successfully used through uniportal VATS to identify peripheral nodules., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 38-year-old man was diagnosed with fibrous dysplasia of the anterolateral segment of the fifth rib by core biopsy. A decision was made to resect the rib by video-assisted thoracic surgery (VATS) taking care to preserve the muscle and overlying myodermal layers. Subsequent reconstruction was done using a straight titanium plate locked in place under thoracoscopic guidance to avoid friction of the plate on the skin and to verify that the transfixed screws would not injure the lung or the pericardium. The patient made an uneventful recovery and was dismissed on day 2 after surgery. Final diagnosis confirmed fibrous dysplasia., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Intrapulmonary percussive ventilation (IPV) aims at clearing retained secretions through oscillary vibrations generated by high frequency bursts of gas delivered into the airways at rates between 200 and 300 breaths per minute and at a delivery pressure of 10 to 20 cm water. In addition, IPV can improve recruitment of alveolar units and deliver aerosolized medications. The use of IPV to resolve challenging postlobectomy localized pneumothoraces is hereafter described., Methods: Between January 2005 and March 2009, four patients with long-term complicated postresectional residual air spaces persisting 6 months (mean, 187 days) after primary surgery were treated by IPV. The type of operation was upper lobectomy and lower lobectomy-wedge resection in 1 and 3 patients, respectively. Mean preoperative and immediate postsurgical forced expiratory volume in the first second of expiration were 2.31 L and 1.49 L, respectively. Mean preoperative and immediate postsurgical forced vital capacity were 3.13 L and 2.1 L, respectively. Patients were subjected to 12-minute-long IPV sessions up to a total of 8 to 12 sessions administered every other day in an outpatient setting., Results: Complete resolution of the spaces within a mean of 22 days of beginning of treatment was noted. The post-IPV forced expiratory volume in the first second of expiration and forced vital capacity were 1.72 and 2.4 liters, respectively. No treatment-related morbidity was observed., Conclusions: Intrapulmonary percussive ventilation can be expected to decisively contribute to resolving long-term localized pneumothoraces after subtotal pulmonary resections in an outpatient setting., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Major tenets in the reconstruction of the anterolateral chest wall include preservation of structural stability and function and coverage of the mediastinal contents. To reach these goals, a rigid support has been advocated by several authors. We describe a patient with extensive anterolateral defect after sternocostal resection of chondrosarcoma. Successful reconstruction was performed by using three metallic transverse plates and an omental flap wrapped onto the plates. This method simplifies reconstruction in comparison with previously described techniques concerning complete solid coverage and leaves several options intact in the event of future recurrences., (Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Traditional 3-port video-assisted thoracoscopic surgery (VATS) in a patient who is awake has been proposed as a breakthrough in the direction of fast tracking patients through routine thoracic surgical procedures. We wanted to explore the possibility of further reducing surgical invasiveness by resecting a peripheral pulmonary nodule with single-access (uniportal) VATS in an awake, nonintubated, nonventilated patient, with selective occlusion of the tributary lobar bronchus., Description: A 47-year-old woman with bilateral peripheral nodules underwent uniportal VATS wedge resection of an undetermined nodule in the right middle lobe. The patient was awake and under mild sedation for the entire procedure. Single-shot epidural regional anesthesia was administered. Under guidance provided by a reusable, portable flexible bronchoscope, a Fogarty balloon was positioned to occlude the right middle lobe bronchus to facilitate collapse of the targeted parenchyma. At the end of the procedure, the chest drain was connected to a portable vacuum system delivering autonomous suction., Evaluation: Awake uniportal VATS resection of peripheral nodules in selected patients is feasible and appears to be safe. Available technology may enable further reduction of costs related to length of hospitalization., Conclusions: The concept of ambulatory thoracic surgery may further evolve by utilizing uniportal VATS in an awake patient to solve the often-challenging diagnostic dilemmas represented by undetermined lung lesions., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Patient satisfaction can be measured by criteria inspired by currently available marketing research methods. Among the latter, qualitative methods can be performed on limited population samples and be based on latent variables, i.e., variables that are not directly observed but deducted from mathematical analysis (i.e., quality of life). Qualitative research methods include the partial least squares (PLS) path modelling aimed at defining optimal linear relations among latent variables in order to assemble the best set of predictions., Methods: In the February-May 2007 period, 73 patients (41 males and 32 females) consecutively discharged from the Division of Thoracic Surgery of the National Cancer Institute at Naples underwent an adaptation of the PLS path modelling by accepting to file an itemized questionnaire on 29 different aspects of hospitalization. The sampled population represented about 32% of all patients operated by a single surgeon and about 21% of all patients admitted to a 12-bed thoracic surgical ward in 2007. Five categories of performance were identified, i.e., quality of the facilities, quality and clarity of provided Information, quality of relationship with surgeons and nurses, quality of the received care, overall patient satisfaction., Results: During the analyzed period, the overall patient satisfaction reached 91% (+/-15). The mean scores were 62% (+/-33), 80% (+/-28), 84% (+/-21), 81% (+/-19), 88% (+/-15) for ward facilities, information provided, relationship with personnel, clinical services, and, perceived quality, respectively. In addition, overall perceived quality, relationship with personnel and the provision of information were the variables with greatest positive impact on patient satisfaction. Conversely, waiting times for radiological procedures, quality of meals and duration of visiting hours adversely affected the level of satisfaction., Conclusions: In the setting of a thorough audit of current clinical practice, PLS path modelling may represent another valuable tool to measure quality in the setting of managed health care since it allows for the identification of areas where the service can be improved.

The objective of the present study was to assess feasibility of single port (uniportal) VATS in the diagnosis and staging of mediastinal nodal enlargements. To this purpose, between January 2002 and October 2005, 13 patients (8 males and 5 females; mean age 54 years) have undergone uniportal VATS sampling of mediastinal nodes either as part of a diagnostic pathway or as a staging procedure for primary lung cancer when either nodal stations were inaccessible to standard mediastinoscopy or in the event of redo nodal biopsy. Sampled stations were the aortopulmonary window (6), subcarinal (1), right paratracheal (5), and, paraesophageal (1) ones. In all cases, sufficient samples were made available for pathological diagnosis. Postoperatively, neither morbidity nor mortality was observed. The median length of stay in the hospital was 1 day. In conclusion we showed that uniportal VATS can be effectively used to achieve diagnosis and staging of mediastinal nodal stations.

The PGF2alpha derivative, latanoprost, is a recent anti-glaucoma drug that has been reported to induce a discrete incidence of increased iris pigmentation in men. The present experiments were made in order to study whether this phenomenon could be influenced by the tyrosinase inhibitor, alpha-methyl-p-tyrosine. Melanin content, melanin production and tyrosinase activity of cultured uveal melanocytes derived from irides of brown or brown-blue color were measured after adding latanoprost at different molar concentration with or without alpha-methyl-p-tyrosine (10(-5)m). It was shown that latanoprost stimulated melanin content, melanin production and tyrosinase activity in a molar range between 10(-7) and 10(-5)m in uveal melanocytes derived from irides of both brown and brown-blue color. The effect seemed to be more pronounced in melanocytes derived from irides of brown-blue color. The adding of alpha-methyl-p-tyrosine completely prevented latanoprost-induced stimulation of melanin production in uveal melanocytes derived from irides of both colors. These results suggest that latanoprost-induced stimulation of melanin production, follows the metabolic pathway involving tyrosinase activity and may be relevant for the therapeutic application of latanoprost in glaucoma in order to reduce its side-effect resulting in increased iris pigmentation., (Copyright 1999 Academic Press.)