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Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment-including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases-currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or-in very selected cases-in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses.
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Background: Bronchoscopy examination is a common clinical diagnostic method. However, due to its unique operational characteristics, the procedure often induces discomfort and pain in patients. The combined use of sufentanil and nalmefene offers advantages in effectively reversing opioid-induced respiratory depression without compromising analgesic effects. However, a comprehensive analysis report on the combined use of different doses of sufentanil and nalmefene in bronchoscopy examinations has not been reported. The aim of this subject is to investigate the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy. Methods: Using computer-based and manual methods to retrieve relevant keywords, we searched the databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang from inception to the present to find studies evaluating the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy examinations. The quality of the included studies was assessed, and meta-analysis was conducted using RevMan 5.3 software. Results: A total of six English-language articles, involving randomized controlled trials and reviews, and comprising 774 participants, were finally included. The control group used conventional therapy, whereas the intervention group used different doses of sufentanil combined with nalmefene. Meta-analysis results indicated that compared to conventional therapy, this approach significantly improved vital signs such as systolic blood pressure [SBP; mean difference (MD) =21.44, P<1×10-5] and diastolic blood pressure (DBP; MD =22.52, P<1×10-5), heart rate (HR; MD =25.16, P<1×10-5), and oxygen saturation (SpO2; MD =30.16, P<1×10-5). A total of 4 studies focused on sedative effects, and that of sufentanil combined with nalmefene was significantly superior to conventional therapy (P<1×10-5). Analysis of adverse events showed that the combined therapy had better outcomes in terms of hypertension and tachycardia incidence compared to the control group (P<0.001, P<1×10-5), and Riker sedation-agitation scale (SAS score) was significantly reduced (P<0.05). However, there were no significant differences in other adverse events (P>0.05). Subgroup analysis showed fewer adverse reactions at 0.4 µg/kg sufentanil concentration compared to 0.2 and 0.8 µg/kg, with only hypertension differing significantly. Conclusions: In clinical practice, considering the use of sufentanil combined with nalmefene can improve patients' experience during bronchoscopy examinations. However, it should be noted that this approach may not be suitable for all patients, and clinicians need to choose appropriate analgesic and sedative methods for bronchoscopy examinations based on patients' conditions and individual differences. Furthermore, it is important to recognize that this study has some limitations and further research is needed to evaluate the efficacy and safety of this approach in other types of endoscopic examinations, as well as to compare the effects and safety of different drug combinations.
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BACKGROUND: Major thoracic trauma represents a life-threatening condition, requiring a prompt multidisciplinary approach and appropriate pathways for effective recovery. While acute morbidity and mortality are well-known outcomes in thoracic-traumatized patients, long-term quality of life in patients surviving surgical treatment has not been widely investigated before. METHODS: Between November 2016 and November 2023, thirty-two consecutive patients were operated on because of thoracic trauma. Age, sex, comorbidities, location and extent of thoracic trauma, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), Organ Injury Scale (OIS), intra and extrathoracic organ involvement, mechanism of injury, type of surgical procedure, postoperative complications, ICU and total length of stay, immediate clinical outcomes and long-term quality of life-by using the EQ-5D-3L scale and Numeric Rate Pain Score (NPRS)-were collected for each patient Results: Results indicated no significant difference in EQOL.5D3L among patients with thoracic trauma based on AIS (p = 0.55), but a significant difference was observed in relation to ISS (p = 0.000011). CONCLUSIONS: ISS is correlated with the EQOL.5D3L questionnaire on long-term quality of life, representing the best prognostic factor-in terms of long-term quality of life-in patients surviving major thoracic trauma surgical treatment.
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Technological development in the field of robotics has meant that, in recent years, more and more thoracic surgery departments have adopted this type of approach at the expense of VATS, and today robotic surgery boasts numerous applications in malignant and benign thoracic pathology. Because autonomic nervous system surgery is a high-precision surgery, it is conceivable that the application of RATS could lead to improved outcomes and reduced side effects, but its feasibility has not yet been thoroughly studied. This review identified three main areas of application: (1) standard thoracic sympathectomy, (2) selective procedures, and (3) nerve reconstruction. Regarding standard sympathectomy and its usual areas of application, such as the management of hyperhidrosis and some cardiac and vascular conditions, the use of RATS is almost anecdotal. Instead, its impact can be decisive if we consider selective techniques such as ramicotomy, optimizing selective surgery of the communicating gray branches, which appears to reduce the incidence of compensatory sweating only when performed with the utmost care. Regarding sympathetic nerve reconstruction, there are several studies, although not conclusive, that point to it as a possible solution to reverse surgical nerve interruption. In conclusion, the characteristics of RATS might make it preferable to other techniques and, particularly, VATS, but to date, the data in the literature are too weak to draw any evidence.
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BACKGROUND Nonunion of a rib fracture can cause chronic pain, and pharmacological pain management may lead to medication dependence. This report describes a 54-year-old man with a chronic cough and painful nonunion fracture of the left posterior 8th rib, managed with minimally invasive surgery and a rib splint. CASE REPORT A 54-year-old man presented with chronic cough-induced left chest wall pain. Three-dimensional chest computed tomography (CT) scan showed a nonunion of a fracture of the left posterior 8th rib. After medical management failure, we proposed a surgical approach with the aim to remove the tissue comprising the nonunion, release the nerve, and stabilize the bone stumps. To avoid the adverse effects of a large incision, we designed a minimally invasive strategy based on ultrasound fracture localization and the use of an intramedullary splint. The pain disappeared immediately after surgery. The patient was discharged in 24 hours. At 6-week follow-up, he was still asymptomatic, and a new CT scan reconfirmed the correct splint position. From the immediate postoperative evaluation until the last follow-up visit, he consistently reported full satisfaction. CONCLUSIONS This report has highlighted the challenges of management of chronic pain in nonunion of a rib fracture, and has described the use of a minimally invasive surgical approach. In this single case, our tailored surgical strategy achieved definitive success in pain management, minimizing postoperative complications/adverse effects and avoiding the addition of pain medications despite a 24-hour hospital stay. Our goal is to share an alternative solution for colleagues facing similar cases.
Subject(s)
Cough , Fractures, Ununited , Minimally Invasive Surgical Procedures , Rib Fractures , Humans , Rib Fractures/surgery , Rib Fractures/complications , Male , Middle Aged , Cough/etiology , Fractures, Ununited/surgery , Chronic Pain/etiology , Chronic Disease , Splints , Tomography, X-Ray Computed , Chronic CoughABSTRACT
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, and surgery is still the first treatment of choice in early and locally advanced cases. One of the iatrogenic complications is the serratus anterior palsy, which could lead to a winged scapula (WS). Unfortunately, the incidence of this deficit in thoracic surgery is unclear. Our primary aim was to determine the incidence of WS in lung cancer patients in a single-center experience. METHODS: We conducted a retrospective analysis of prospectively collected data with patients eligible for oncological thoracic surgery from March 2013 until January 2014. A physical evaluation of the WS was performed pre- and postoperatively, at the discharge and after 1 year of follow-up. RESULTS: A total of 485 patients were evaluated; 135 (27.8%) showed WS. Longer operative time (p < 0.0001), type of surgery (p < 0.0001), lymphadenectomy (p < 0.0001), and neoadjuvant treatment prior surgery (p = 0.0005) were significantly related to the WS injury. Multivariable analysis showed that type of surgery was significantly associated with WS (p < 0.0001). After 1 year, 41.6% still had WS. CONCLUSION: The incidence of WS was similar to the literature. As WS incidence is underdiagnosed, assessment and correct education about possible deficits or impairments should be improved. Moreover, when a minimally invasive approach is not planned, it is a good clinical practice to discuss surgical strategies with surgeons to reduce this deficit.
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BACKGROUND: We compared computed tomography (CT) images and holograms (HG) to assess the number of arteries of the lung lobes undergoing lobectomy and assessed easiness in interpretation by radiologists and thoracic surgeons with both techniques. METHODS: Patients scheduled for lobectomy for lung cancer were prospectively included and underwent CT for staging. A patient-specific three-dimensional model was generated and visualized in an augmented reality setting. One radiologist and one thoracic surgeon evaluated CT images and holograms to count lobar arteries, having as reference standard the number of arteries recorded at surgery. The easiness of vessel identification was graded according to a Likert scale. Wilcoxon signed-rank test and κ statistics were used. RESULTS: Fifty-two patients were prospectively included. The two doctors detected the same number of arteries in 44/52 images (85%) and in 51/52 holograms (98%). The mean difference between the number of artery branches detected by surgery and CT images was 0.31 ± 0.98, whereas it was 0.09 ± 0.37 between surgery and HGs (p = 0.433). In particular, the mean difference in the number of arteries detected in the upper lobes was 0.67 ± 1.08 between surgery and CT images and 0.17 ± 0.46 between surgery and holograms (p = 0.029). Both radiologist and surgeon showed a higher agreement for holograms (κ = 0.99) than for CT (κ = 0.81) and found holograms easier to evaluate than CTs (p < 0.001). CONCLUSIONS: Augmented reality by holograms is an effective tool for preoperative vascular anatomy assessment of lungs, especially when evaluating the upper lobes, more prone to anatomical variations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04227444 RELEVANCE STATEMENT: Preoperative evaluation of the lung lobe arteries through augmented reality may help the thoracic surgeons to carefully plan a lobectomy, thus contributing to optimize patients' outcomes. KEY POINTS: ⢠Preoperative assessment of the lung arteries may help surgical planning. ⢠Lung artery detection by augmented reality was more accurate than that by CT images, particularly for the upper lobes. ⢠The assessment of the lung arterial vessels was easier by using holograms than CT images.
Subject(s)
Augmented Reality , Holography , Lung Neoplasms , Pulmonary Artery , Tomography, X-Ray Computed , Humans , Female , Male , Tomography, X-Ray Computed/methods , Aged , Prospective Studies , Lung Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Middle Aged , Holography/methods , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/anatomy & histology , Imaging, Three-Dimensional , Reference Standards , Lung/diagnostic imaging , Lung/blood supply , Lung/surgeryABSTRACT
Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9-12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.
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Pleural mesothelioma is a rare and aggressive cancer that affects the pleura. In recent years, there has been increasing interest and attention in detecting and diagnosing early-stage or precancerous forms of mesothelioma because of its severe prognosis and short life expectancy at the time of diagnosis. Mesothelioma in situ represents a clear opportunity to improve and innovate the diagnostic approach and the multimodality treatment of mesothelioma: the diagnosis of pleural mesothelioma at the 'in-situ phase' means early disease detection and thus paves the way to new possible curable strategies. Since 2021, when mesothelioma in situ was finally identified and described as a new histological entity, its diagnosis and management became a challenge and the subject of ongoing research; several aspects remain open and still outstanding as regards diagnostic techniques, time and probability of progression, need for and methods of follow up, aggressive and early surgery. This narrative review aims to provide a comprehensive overview of mesothelioma in situ covering its definition, risk factors, diagnostic criteria, and tricky aspects of early detection. It also highlights its clinical significance, new perspectives, and potential future indications in the context of pleural mesothelioma multidisciplinary management.
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The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues, thus incrementing drug effects and, at the same time, reducing the damage of non-involved tissues to cytotoxic agents. Mesenchymal stromal cells (MSC) represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells. During the last year, they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cells, thus optimizing cytotoxic action on cancer cells, while significantly reducing adverse side effects on healthy cells. MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors, especially for those with unsatisfactory prognosis and limited treatment options available. Although some experimental models have been successfully developed, phase I clinical studies are needed to confirm this potential application of cell therapy, in particular in the case of primary and secondary lung cancers.
Subject(s)
Antineoplastic Agents , Lung Neoplasms , Mesenchymal Stem Cells , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Lung Neoplasms/pathology , Mesenchymal Stem Cells/pathology , TechnologyABSTRACT
The hemiclamshell incision is a combination of partial median sternotomy and anterolateral thoracotomy, allowing excellent exposure of mediastinum, one pleural cavity and the neck. It can be used for superior sulcus tumors with mediastinal involvement or to resect bulky mediastinal lesions or lesions requiring cervical, mediastinal and pleural exposition. Although the vast majority of mediastinal lesions can now be approached by minimally invasive techniques, the hemiclamshell incision still plays a pivotal role in the case of bulky lesions involving cervical, mediastinal and pleural cavities. In the case of cardiac or great vessel involvement, the procedure should be performed in experienced high-volume centers with the availability of cardio-pulmonary bypass, extra-corporeal membrane oxygenator or venous shunts. Although the vast majority of mediastinal lesions can now be approached by minimally invasive techniques, the hemiclamshell incision still plays a pivotal role in the case of bulky lesions involving cervical, mediastinal and pleural cavities. It consists of a combination of subtotal median vertical sternotomy and antero-lateral thoracotomy in the 4th intercostal space, providing excellent exposure of the neck, mediastinum and one pleural cavity. The objective of this paper is to describe the standard steps for performing a hemiclamshell incision by using modern devices and technology which contribute to make this procedure easier, faster and safer.
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The transmanubrial musculoskeletal sparing approach (TMA) is commonly used for resecting apical lung tumours with vascular involvement. Non-neoplastic conditions which might require surgical exploration of the thoracic outlet include the 'cervical rib', a clinical condition consisting of an additional rib forming above the first rib and growing from the base of the neck just above the clavicle. Type 1 cervical rib-when a complete cervical rib articulates with the first rib or manubrium of the sternum-is the most challenging scenario where the subclavian artery can be damaged by continuous compression due to the narrow space between clavicle, first rib and supernumerary cervical rib, requiring prosthetic reconstruction of the involved tract. Here, we describe a modified TMA in which the incision in the neck is conducted posteriorly to the sternocleidomastoid muscle, thus allowing safe dissection of the superior and middle trunk of the brachial plexus.
Subject(s)
Cervical Rib , Lung Neoplasms , Plastic Surgery Procedures , Thoracic Outlet Syndrome , Humans , Subclavian Artery/diagnostic imaging , Subclavian Artery/surgery , Subclavian Artery/pathology , Cervical Rib/pathology , Cervical Rib/surgery , Lung Neoplasms/pathology , Ribs/surgery , Ribs/pathology , Thoracic Outlet Syndrome/etiology , Thoracic Outlet Syndrome/pathology , Thoracic Outlet Syndrome/surgeryABSTRACT
BACKGROUND: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized. METHODS: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan-Meier curves were used to determine survival. RESULTS: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76-90.97), with no difference (p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications (p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results. CONCLUSIONS: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications (p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy.
Subject(s)
Lung Neoplasms , Humans , Incidence , Retrospective Studies , Lung Neoplasms/pathology , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Risk FactorsABSTRACT
Stem cells are undifferentiated cells presenting extensive self-renewal features and the ability to differentiate "in vitro" and "in vivo" into a range of lineage cells, like chondrogenic, osteogenic and adipogenic lineages when cultured in specific inducing media. Two major domains of clinical applications of stem cells in thoracic surgery have been investigated: regenerative medicine, which is a section of translational research in tissue engineering focusing on the replacement, renewal or regeneration of cells, tissues and organs to re-establish damaged physiologic functions; drug loading and delivery, representing a new branch proposing stem cells as carriers to provide selected districts with anti-cancer agents for targeted treatments.
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Medical treatment has changed drastically in recent years, especially for advanced stages of non-small-cell lung cancer (NSCLC), for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. This single-center retrospective study aimed to analyze the outcome predictors, the surrogate outcomes, and the patient-reported outcomes after neoadjuvant immunotherapy for initially unresectable NSCLC. Patients affected by an initially unresectable NSCLC and identified between March 2014 and December 2021 who received immunotherapy alone or in combination with platinum-based chemotherapy and/or radiotherapy were collected. Overall survival (OS) and disease-free survival (DFS) were estimated according to the Kaplan-Meier method. Patient-reported outcomes were recorded using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QoL) Group questionnaire-Lung Cancer 29 Module to compare differences in symptoms and QoL at two different times, 30 days and 1 year after surgery. Surgical, pathological records, and patient-reported outcomes (at 30 days and 1 year after surgery) were reviewed. Complete pathological remission was achieved in 7 patients (36.8%) and major pathological remission in 3 patients (15.7%). The median overall survival in the study group is 19 months (range: 2-57.4). Of 19 patients, 16 (84.2%) are alive to date, of which 2 (10.5%) have a local recurrence. At 30 days from surgery, the main symptoms reported by EORTC Module were coughing, shortness of breath, the side effect of treatment, fear of progression, and surgery-related problems. Induction immunotherapy with or without chemotherapy can be considered for unresectable locally advanced NSCLC, and after the downstaging, the possibility of surgery could be re-evaluated in a multidisciplinary setting with high rates of R0 resection. In this selected and highly motivated group of patients, the QoL and symptoms after salvage surgeries are acceptable and even better than those reported in the literature.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Retrospective Studies , Quality of Life , Immunotherapy , Patient Reported Outcome Measures , Neoplasm StagingABSTRACT
Background: In the treatment of Non-Small Cell Lung Cancer (NSCLC) the combination of Immuno- Oncotherapy (IO) and chemotherapy (CT) has been found to be superior to IO or CT alone for patients' survival. Patients and clinicians are confronted with a preference sensitive choice between a more aggressive treatment with a greater negative effect on quality of life versus alternatives that are less effective but have fewer side effects. Objectives: The aims of this study were to: (a) quantify patients' preferences for relevant attributes related to Immuno-Oncotherapy treatment alternatives, and (b) evaluate the maximum acceptable risk (MAR)/Minimum acceptable benefit (MAB) that patients would accept for treatment alternatives. Methods: An online preference survey using discrete-choice experiment (DCE) was completed by NSCLC patients from two hospitals in Italy and Belgium. The survey asked patients' preferences for five patient- relevant treatment attributes. The DCE was developed using a Bayesian D-efficient design. DCE analyses were performed using mixed logit models. Information regarding patient demographics, health literacy, locus of control, and quality of life was also collected. Results: 307 patients (158 Italian, 149 Belgian), stage I to IV, completed the survey. Patients preferred treatments with a higher 5-year survival chance as the most important attribute over all the other attributes. Preference heterogeneity for the attribute weights depended on health literacy, patients' age and locus of control. Patients were willing to accept a substantially increased risks of developing side effects in exchange for the slightest increase (1%) in the chance of surviving at least 5 years from the diagnosis of cancer. Similarly, patients were willing to accept a switch in the mode of administration or complete loss of hair to obtain an increase in survival. Conclusion: In this study, the proportion of respondents who systematically preferred survival over all other treatment attributes was particularly high. Age, objective health literacy and locus of control accounted for heterogeneity in patients' preferences. Evidence on how NSCLC patients trade between survival and other NSCLC attributes can support regulators and other stakeholders on assessing clinical trial evidence and protocols, based on patients' conditions and socio-demographic parameters.
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Pancoast tumors, also defined as superior sulcus tumors, still represent a complex clinical condition requiring high technical surgical skills within more articulated multimodality treatment. The morbidity and mortality rates after Pancoast tumor treatments range from 10 to 55% and 0 to 7%, respectively, and the 5-year survival rate has significantly improved in recent years thanks to the advancement of treatments. Although a multimodality approach combining chemotherapy, radiotherapy, and surgery allows for radical resection and effective local control in the vast majority of patients, many patients cannot receive surgical resection or complete the whole programmed therapeutic regimen. Systemic relapse, particularly cerebral recurrence, still poses a significant issue in this cohort of patients. Surgical resection still plays a pivotal role within the multimodality approach. Here, we focus on surgical approaches to both anterior and posterior Pancoast tumors: the anterior transclavicular approach (Dartevelle); the anterior transmanubrial approach (Grunenwald-Spaggiari); the anterior trap-door approach (Masaoka, Nomori); the posterior approach (Shaw-Paulson); the hemiclamshell approach; and hybrid approaches. Global clinical condition, tumor histology, and long-term perspectives should always be taken into consideration when embarking on such a demanding oncologic scenario.
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Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone. An in vivo approach to treat in situ mesothelioma xenografts using a minimal amount of 106 mesenchymal stromal cells loaded with Paclitaxel showed the same efficacy of a systemic administration of 10 mg/kg of Paclitaxel. These data strongly support drug delivery system by mesenchymal stromal cells as a useful approach against many solid tumors. We look with interest at the favourable opinion recently expressed by the Italian Drug Agency on the procedure for the preparation of mesenchymal stromal cells loaded with Paclitaxel in large-scale bioreactor systems and their storage until clinical use. This new Advanced Medicinal Therapy Product, already approved for a Phase I clinical trial on mesothelioma patients, could pave the way for mesenchymal stromal cells use as drug delivery system on other solid tumors for adjuvant therapy associated with surgery and radiotherapy.
Subject(s)
Mesenchymal Stem Cells , Mesothelioma, Malignant , Mesothelioma , Humans , Paclitaxel , Cell Line, Tumor , Mesothelioma/drug therapyABSTRACT
In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.
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Many new treatment modalities for non-small-cell carcinoma (NSCLC) have been described in the last two decades. Surgical resections remain the gold standard for early stages and may be considered for locally advanced tumors. Medical treatment has changed drastically in recent years, especially for advanced stages, for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. The addition of radical surgical resection following immunotherapy or immuno-chemotherapy is feasible and safe with low surgical-related mortality and morbidity in selected patients with initially unresectable NSCLC. However, data from multiple ongoing trials with overall survival as the primary endpoint should be awaited before this strategy is introduced into the standard of care.