ABSTRACT
Thymic stromal lymphopoietin (TSLP), mainly expressed by epithelial cells, plays a central role in asthma. In humans, TSLP exists in two variants: the long form TSLP (lfTSLP) and a shorter TSLP isoform (sfTSLP). Macrophages (HLMs) and mast cells (HLMCs) are in close proximity in the human lung and play key roles in asthma. We evaluated the early proteolytic effects of tryptase and chymase released by HLMCs on TSLP by mass spectrometry. We also investigated whether TSLP and its fragments generated by these enzymes induce angiogenic factor release from HLMs. Mass spectrometry (MS) allowed the identification of TSLP cleavage sites caused by tryptase and chymase. Recombinant human TSLP treated with recombinant tryptase showed the production of 1-97 and 98-132 fragments. Recombinant chymase treatment of TSLP generated two peptides, 1-36 and 37-132. lfTSLP induced the release of VEGF-A, the most potent angiogenic factor, from HLMs. By contrast, the four TSLP fragments generated by tryptase and chymase failed to activate HLMs. Long-term TSLP incubation with furin generated two peptides devoid of activating property on HLMs. These results unveil an intricate interplay between mast cell-derived proteases and TSLP. These findings have potential relevance in understanding novel aspects of asthma pathobiology.
Subject(s)
Asthma , Thymic Stromal Lymphopoietin , Humans , Tryptases , Chymases , Angiogenesis Inducing Agents , Serine Proteases , CytokinesABSTRACT
BACKGROUND: Macrophages are the predominant immune cells in the human lung and play a central role in airway inflammation, including asthma and chronic obstructive pulmonary disease (COPD). Thymic stromal lymphopoietin (TSLP), a pleiotropic cytokine mainly expressed by bronchial epithelial cells, plays a key role in asthma and COPD pathobiology. TSLP exists in two variants: the long form (lfTSLP) and a shorter TSLP isoform (sfTSLP). We aimed to localize TSLP in human lung macrophages (HLMs) and investigate the mechanisms of its release from these cells. We also evaluated the effects of the two variants of TSLP on the release of angiogenic factor from HLMs. METHODS: We employed immunofluorescence and Western blot to localize intracellular TSLP in HLMs purified from human lung parenchyma. HLMs were activated by T2-high (IL-4, IL-13) and T2-low (lipopolysaccharide: LPS) immunological stimuli. RESULTS: TSLP was detected in HLMs and subcellularly localized in the cytoplasm. IL-4 and LPS induced TSLP release from HLMs. Preincubation of macrophages with brefeldin A, known to disrupt the Golgi apparatus, inhibited TSLP release induced by LPS and IL-4. lfTSLP concentration-dependently induced the release of vascular endothelial growth factor-A (VEGF-A), the most potent angiogenic factor, from HLMs. sfTSLP neither activated nor interfered with the activating property of lfTSLP on macrophages. CONCLUSIONS: Our results highlight a novel immunologic circuit between HLMs and TSLP. Given the central role of macrophages in airway inflammation, this autocrine loop holds potential translational relevance in understanding innovative aspects of the pathobiology of asthma and chronic inflammatory lung disorders.
Subject(s)
Asthma , Cytokines , Interleukin-4 , Lipopolysaccharides , Macrophages, Alveolar , Pulmonary Disease, Chronic Obstructive , Thymic Stromal Lymphopoietin , Humans , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/immunology , Asthma/metabolism , Asthma/immunology , Cytokines/metabolism , Interleukin-4/metabolism , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/immunology , Lipopolysaccharides/pharmacology , Interleukin-13/metabolism , Vascular Endothelial Growth Factor A/metabolism , Cells, CulturedABSTRACT
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.
Subject(s)
Interdisciplinary Communication , Lung Neoplasms , Humans , Prospective Studies , Risk Management , Patient Care TeamABSTRACT
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.
ABSTRACT
Increasing evidence suggests that liquid biopsy might play a relevant role in the management of metastatic non-small cell lung cancer (NSCLC) patients. Here, we show how the Molecular Tumor Board (MTB) in our cancer center employed liquid biopsy to support therapeutic decisions in a patient with NSCLC carrying a rare EGFR mutation. A 44-year-old woman, never-smoker with an EGFR, ALK, and ROS1-negative lung adenocarcinoma and multiple brain metastases received systemic therapy and surgery before being referred to our Institute. The MTB suggested NGS testing of tumor biopsy that revealed a rare exon-20 EGFR insertion (p.His773dup; c.2315_2316insCCA) and EGFR amplification. The MTB recommended treatment with erlotinib and follow-up with liquid biopsy, by using both cell-free DNA (cfDNA) and circulating tumor cells (CTCs). An increase of EGFR mutation levels in cfDNA revealed resistance to treatment about 6 months before clinical progression. Extremely low levels of EGFR p.T790M were detected at progression. Based on preclinical data suggesting activity of osimertinib against EGFR exon-20 insertions, the MTB recommended treatment with brain and bone radiotherapy and osimertinib. A dramatic reduction of EGFR mutation levels in the cfDNA was observed after 4 weeks of treatment. The PET scan demonstrated a metabolic partial remission that was maintained for 9 months. This case supports the evidence that liquid biopsy can aid in the management of metastatic NSCLC. It also suggests that treatment with osimertinib might be a therapeutic option in patients with EGFR exon-20 insertions when a clinical trial is not available.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell-Free Nucleic Acids , Lung Neoplasms , Adult , Aniline Compounds/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , ErbB Receptors/therapeutic use , Exons/genetics , Female , Humans , Liquid Biopsy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/geneticsABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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).
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Humans , Lung Neoplasms/pathology , Randomized Controlled Trials as Topic , Survival RateABSTRACT
Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype-phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration. These insights provide novel information in oligometastatic CRC biology and new perspectives for cancer monitoring and anti-cancer therapeutic strategies.
Subject(s)
Colorectal Neoplasms/genetics , Lung Neoplasms/secondary , Female , Humans , Male , Neoplasm Metastasis , Tumor MicroenvironmentABSTRACT
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.
ABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Environmental Pollutants/toxicity , Lung Neoplasms/surgery , Aged , Carcinoma, Non-Small-Cell Lung/chemically induced , Female , Humans , Italy , Lung Neoplasms/chemically induced , Male , Middle Aged , Prognosis , Retrospective Studies , Survival RateABSTRACT
OBJECTIVES: Breath composition may be suggestive of different conditions. E-nose technology has been used to profile volatile organic compounds (VOCs) pattern in the breath of patients compared with that of healthy individuals. BIOsensor-based multisensorial system for mimicking NOse, Tongue and Eyes (BIONOTE) technology differs from Cyranose® based on a set of separate transduction features. On the basis of our previously published experience, we investigated the discriminating ability of BIONOTE in a high-risk population enrolled in a lung cancer screening programme. METHODS: One hundred individuals were selected for BIONOTE based on the attribution to the high-risk category (i.e. age, smoking status, chronic obstructive pulmonary disease status) of the University Campus Bio-Medico lung screening programme. We used a measure chain consisting of (i) a device named Pneumopipe (EU patent: EP2641537 (A1):2013-09-25) able to catch exhaled breath by an individual normally breathing into it and collect the exhalate onto an adsorbing cartridge; (ii) an apparatus for thermal desorption of the cartridge into the sensors chamber and (iii) a gas sensor array which is part of a sensorial platform named BIONOTE for the VOCs mixture analysis. Partial least square (PLS) has been used to build up the model, with Leave-One-Out cross-validation criterion. Each breath fingerprint analysis costs 10. RESULTS: The overall sensitivity and specificity were 86 and 95%, respectively, delineating a substantial difference between patients and healthy individuals. CONCLUSIONS: Our preliminary data show that BIONOTE technology may be used to reduce false-positive rates resulting from lung cancer screening with low-dose computed tomography in a cost-effective fashion. The model will be tested on a larger number of patients to confirm the reliability of these results.
Subject(s)
Early Detection of Cancer/methods , Electronic Nose , Lung Neoplasms/diagnosis , Female , Humans , Male , Middle Aged , ROC Curve , Sensitivity and SpecificityABSTRACT
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.
Subject(s)
Bone Plates , Ribs/surgery , Thoracic Wall/surgery , Titanium , Adult , Bone Neoplasms/surgery , Female , Fibromatosis, Aggressive/surgery , Humans , Prosthesis Design , Plastic Surgery Procedures/methods , Thoracic Surgical Procedures/methodsABSTRACT
BACKGROUND: Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be 'major', characterized by a single tumor showing two different histologic types, and 'minor', due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. METHODS: 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. RESULTS: 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. CONCLUSION: Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes.
Subject(s)
Adenocarcinoma/enzymology , Adenocarcinoma/genetics , ErbB Receptors/genetics , Gene Rearrangement , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Mutation , Receptor Protein-Tyrosine Kinases/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Anaplastic Lymphoma Kinase , Female , Humans , Lung Neoplasms/pathology , Male , Middle AgedSubject(s)
Hernia/etiology , Lung Diseases/etiology , Surgical Mesh , Thoracotomy/adverse effects , Female , Hernia/diagnostic imaging , Herniorrhaphy/methods , Humans , Lung Diseases/diagnostic imaging , Mediastinum/surgery , Middle Aged , Rare Diseases , Thoracotomy/methods , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
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.
Subject(s)
Atrial Fibrillation/etiology , Electrocoagulation/instrumentation , Electrosurgery/instrumentation , Lymph Node Excision/methods , Mediastinum/surgery , Pneumonectomy/methods , Aged , Electrocoagulation/adverse effects , Electrocoagulation/methods , Electrosurgery/adverse effects , Electrosurgery/methods , Female , Humans , Length of Stay/statistics & numerical data , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lymph Node Excision/adverse effects , Male , Middle Aged , Pilot Projects , Pneumonectomy/adverse effectsABSTRACT
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.
Subject(s)
Negative-Pressure Wound Therapy/statistics & numerical data , Prostheses and Implants , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Thoracic Neoplasms/surgery , Thoracoplasty/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Morbidity/trends , Retrospective Studies , Thoracoplasty/instrumentation , Treatment Outcome , Young AdultABSTRACT
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.