Potential biomarkers for immunotherapy in non-small-cell lung cancer.

For individuals with advanced or metastatic non-small cell lung cancer (NSCLC), the primary treatment is platinum-based doublet chemotherapy. Immune checkpoint inhibitors (ICIs), primarily PD-1/PD-L1 and CTLA-4, have been found to be effective in patients with NSCLC who have no EGFR/ALK mutations. Furthermore, ICIs are considered a standard therapy. The quantity of fresh immunogenic antigens discovered by cytotoxic T cells was measured by PD-L1 expression and tumor mutational burden (TMB), which were the first biomarkers assessed in clinical trials. However, immunotherapy did not have response efficacy markers similar to targeted therapy, highlighting the significance of newly developed biomarkers. This investigation aims to review the research on immunotherapy for NSCLC, focusing primarily on the impact of biomarkers on efficacy prediction to determine whether biomarkers may be utilized to evaluate the effectiveness of immunotherapy.

Deepening the Knowledge of ROS1 Rearrangements in Non-Small Cell Lung Cancer: Diagnosis, Treatment, Resistance and Concomitant Alterations.

ROS proto-oncogene 1 (ROS1) rearrangements are reported in about 1-2% of non-squamous non-small-cell lung cancer (NSCLC). After efficacy of crizotinib was demonstrated, identification of ROS1 translocations in advanced disease became fundamental to give patients the chance of specific and effective treatment. Different methods are available for detection of rearrangements, and probably the real prevalence of ROS1 rearrangements is higher than that reported in literature, as our capacity to detect gene rearrangements is improving. In particular, with next generation sequencing (NGS) techniques, we are currently able to assess multiple genes simultaneously with increasing sensitivity. This is leading to overcome the "single oncogenic driver" paradigm, and in the very near future, the co-existence of multiple drivers will probably emerge more frequently and represent a therapeutic issue. Since recently, crizotinib has been the only available therapy, but today, many other tyrosine kinase inhibitors (TKI) are emerging and seem promising both in first and subsequent lines of treatment. Indeed, novel inhibitors are also able to overcome resistance mutations to crizotinib, hypothesizing a possible sequential strategy also in ROS1-rearranged disease. In this review, we will focus on ROS1 rearrangements, dealing with diagnostic aspects, new therapeutic options, resistance issues and the coexistence of ROS1 translocations with other molecular alterations.

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2-4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

Donor surfactant protein A2 polymorphism and lung transplant survival.

PURPOSE: Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the surfactant protein (SP)-A gene of the donor lung allograft and recipient post-transplant outcome. METHODS: Lung-transplant patients (n=192) were prospectively followed-up with pulmonary function tests, bronchoscopies with bronchoalveolar lavage and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. RESULTS: SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SP-A2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at 1 year (log-rank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for 1-year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on 1-year survival no significance was observed, indicating that the survival difference was due to the first year's outcome associated with the 1A1 variant. CONCLUSION: Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at 1 year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.

Is laser-assisted resection preferable to lobectomy for pulmonary metastasectomy?

The aim of this study was to investigate if laser-assisted resection is appropriate for large and/or central lung metastases, when stapler wedge resection is not feasible, to determine whether this technique can be an alternative to lobectomy. All patients who underwent laser-assisted resection for large and/or central metastases were selected for the study. For comparison, patients who underwent lobectomy for metastases between 2005 and 2017 were reviewed. All resections were performed with a 1318-nm Nd:YAG laser. Perioperative features and long-term oncological outcomes were investigated. Some aspects and drawbacks of laser resection were also investigated. Among 89 patients, 42 (47%) underwent laser resection and 47 underwent lobectomy. Complete resection was achieved in 91% of laser resections and in 98% of lobectomies. The operative time, postoperative drainage time, and length of stay were significantly shorter in patients who underwent laser resection than in those who underwent lobectomy. Severe postoperative complications tended to be more frequent after lobectomy. The 5-year survival was 66% and 54% after laser resection and lobectomy respectively; the 5-year disease-free survival was 35% and 32% after laser resection and lobectomy respectively. No differences were found in long-term outcomes between the two techniques. Our experience showed that laser resection, when performed for large/central metastases, resulted in comparable survival and obtained better perioperative outcomes with respect to lobectomy. We believe that laser resection can be proposed as a reliable and advantageous lung-sparing technique, as an alternative to lobectomy for metastasectomy, when stapler wedge resection is not feasible.

Effectiveness of antireflux surgery for the cure of chronic cough associated with gastroesophageal reflux disease.

BACKGROUND: The effectiveness of surgical therapy for chronic cough secondary to gastroesophageal reflux disease remains controversial. The purpose of this study was to assess the efficacy of surgery and to identify the preoperative clinical profile that could predict the positive effects of treatment on chronic cough. STUDY DESIGN: Of 299 patients who underwent antireflux surgery between 1995 and 2010, 67 patients were affected by chronic cough and typical symptoms. In addition, 83 patients with typical symptoms were selected to form the control group, according to the parameters of age, sex, and the period of surgical activity. Preoperatively, all patients underwent a workup, including symptom assessment, barium swallow, upper gastrointestinal endoscopy, esophageal manometry, and 24-h pH recording or intraluminal impedance/pH monitoring in the absence of esophagitis. Patients with chronic cough also were administered a high-resolution computed tomography scan of the chest, a methacholine challenge test, and spirometry. Surgery was performed on patients positive for gastroesophageal reflux disease and negative for pulmonary diseases. The patients were followed up for a median of 84 months after surgery. RESULTS: No significant differences in preoperative reflux symptoms or esophagitis were found between the two groups. After surgery, chronic cough was absent in 57 (85 %) patients. Of the ten patients who still reported chronic cough, reflux symptoms relapsed in five, two of whom developed esophagitis. In the other five patients, typical symptoms were absent, and their chronic cough had improved but had not disappeared. CONCLUSIONS: Surgery is effective for the treatment of chronic cough secondary to gastroesophageal reflux disease, particularly if associated with severe and long-standing typical symptoms.

Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study.

BACKGROUND: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. METHODS: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. RESULTS: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50-75%)-measured with high-resolution computer tomography-compared to those with a lower extent (0-25%) (difference between means = 25.74 ± 6.72, p = 0.004). CONCLUSIONS: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.

A novel drainage strategy using chest tube plus pleural catheter in uniportal upper lobectomy: A randomized controlled trial.

BACKGROUND: In this study we explored whether one pleural catheter plus single chest tube drainage could achieve a noninferior drainage effect when compared with the traditional two chest tubes in uniportal video-assisted thoracoscopic surgery (VATS) for an upper pulmonary lobectomy. METHODS: Patients that underwent an upper pulmonary lobectomy from January to November 2020 were enrolled in this single-center, randomized, open-label, noninferiority trial. Prior to closure, patients were randomized to an intervention group who received an improved drainage strategy involving one pleural catheter with one chest tube (24 Fr), while traditional double chest tube drainage was applied for the control group. RESULTS: A total of 390 patients entered the study, although 190 were excluded for changing nonuniportal surgical approaches or opting for nonlobectomy resections. Finally, 200 patients were randomized (100 in the intervention group and 100 in the control group). The baseline demographic and clinical characteristics were comparable between the groups. The incidence of pneumothorax in the intervention and control groups was similar on postoperative Day 1 (noninferiority, 10% vs. 13%, p = 0.658). In addition, there were no significant differences in secondary outcomes such as incidence of pneumothorax by Day 30, postoperative chest tube/pleural catheter removal time, amount of drainage on Day 1, total amount of drainage after operation, or postoperative hospitalization. A significantly lower pain score was observed in the intervention group (3.33 ± 0.68 vs. 3.68 ± 0.94, p = 0.003). CONCLUSIONS: The new strategy is noninferior to double chest tube drainage after an upper pulmonary lobectomy offers superior pain control, and is recommended for an upper lobectomy by uniportal VATS.

Reconstructive Surgery of Pressure Injuries in Spinal Cord Injury/Disorder Patients: Retrospective Observational Study and Proposal of an Algorithm for the Flap Choice.

Pressure injuries (PIs) are a common complication in patients with spinal cord injury/disorder (SCI/D), and deep PIs require surgical treatment consisting of wide debridement and adequate reconstruction. We conducted a retrospective observational study at a tertiary rehabilitation hospital for SCI/D in Italy with the aim of describing the incidence and associated risk factors of postoperative complications in individuals with SCI/D presenting with chronic deep PIs, treated with a specific flap selection algorithm based on the site of the defect, the presence of scars from previous surgeries, and the need to spare reconstructive options for possible future recurrences. Medical records of surgical procedures performed on SCI/D patients with fourth-degree PIs, according to NPUAP classification (National Pressure Ulcer Advisory Panel), between July 2011 and January 2018 were reviewed. A total of 434 surgical procedures for fourth-degree PIs in 375 SCI/D patients were analyzed. After a mean follow-up of 21 months (range 12-36), 59 PIs (13.6%) had minor complications, and 17 (3.9%) had major complications requiring reoperation. The sacral site and muscular and musculocutaneous flaps were significant risk factors for postoperative complications. Six patients (1.4%) had a recurrence. The choice of flap correlates with the outcome of decubitus reconstruction. Therefore, reconstructive planning should be based on established principles.

Circulating and Tumor-Associated Neutrophils in the Era of Immune Checkpoint Inhibitors: Dynamics, Phenotypes, Metabolism, and Functions.

Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional population of terminally differentiated, short-living cells. During the last decade, the use of cutting-edge, single-cell technologies has revolutionized the classical view of these cells, unmasking their phenotypic and functional heterogeneity. In this review, we summarize the emerging concepts in the field of neutrophils in cancer, by reviewing the recent literature on the heterogeneity of both circulating neutrophils and tumor-associated neutrophils, as well as their possible significance in tumor prognosis and resistance to immune checkpoint inhibitors.

Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.

Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC.

Thymoma and Thymic Carcinoma: Surgical Resection and Multidisciplinary Treatment.

Thymoma and thymic carcinoma are the most common tumors of the anterior mediastinum and a relatively rare type of thoracic cancer. The prerequisite for surgery is clinical staging and operative evaluation, both of which are based on medical imaging. The best strategy for treating a thymic epithelial tumor is surgical resection of the organ and surrounding tissue. Thymectomy modalities vary, including open surgery and minimally invasive surgery, and surgeons have used various innovations to better meet the needs of the procedure; therefore, it is critical to select the appropriate procedure based on the patient's characteristics. Evaluation of resectability is the first step of surgical resection for thymic tumors without distant metastasis. The decision regarding unresectability should be made carefully. During subsequent chemotherapy or chemoradiotherapy, reevaluation of whether an area is resectable or not remains essential. Despite numerous technological advances in the surgical treatment of thymic tumors, several contentious issues remain, including the selection of surgical approaches for difficult cases, the selection of video-assisted thoracoscopic approaches, the evaluation of resectability, minimally invasive surgery for locally advanced thymic tumors, lymphadenectomy in thymic tumors, neoadjuvant therapy for thymic tumors, debulking surgery, and salvage surgery. In solving these problems, the surgeon's judgment, surgical experience, and surgical skills are especially important.

Proteomic profiling of formalin-fixed paraffine-embedded tissue reveals key proteins related to lung dysfunction in idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues. Methods: We further determined the protein expression according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins. Results: After the pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor ß (TGF-ß) signaling pathways strongly associated with IPF onset and progression. Five proteins were significantly over- expressed in the lung of IPF patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLCO<55) compared to controls; these were lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan (OGN) that might play a key role in the fibrogenic processes. Discussion: Our work showed that the analysis of FFPE samples was able to identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or involved in the immune landscape of lung cancer, thus making possible common mechanisms between lung carcinogenesis and fibrosis progression, two pathological conditions at risk for each other in the real life.

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments.

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network among them and the tumor microenvironment. In particular, cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment with different functions, including matrix deposition and remodeling, extensive reciprocal signaling interactions with cancer cells and crosstalk with immunity. The settings of new markers and the definition of the molecular connections may present new avenues, not only for fighting cancer but also for the definition of more tailored therapies.

The role of Ivor Lewis esophagectomy in the treatment of achalasia with megaesophagus: A case report.

Introduction: Achalasia with megaesophagus is a pathology characterized by widespread and irregular dilation of the esophageal lumen. In most cases, this dilation is caused by contraction and subsequent failed relaxation of the lower esophageal sphincter (LES). It may be associated with a partial or complete slowing of the esophageal peristalsis. Case overview: We present the case of a 58-year-old woman who developed dysphagia, regurgitation, and substantial weight loss (11 kg) over a span of 1 year. Symptomatic achalasia with megaesophagus was diagnosed following chest and abdominal computed tomography (CT) with contrast and transit RX with gastrografin and esophageal manometry. The patient refuse all minimally endoscopic treatments and opted straightly for the treatment with esophagectomy sec. Ivor-Lewis. At the 6-month follow-up, the patient appeared in excellent general clinical condition and oral gastrografin radiography (OGR) showed good channeling. Discussion: Patients require medical attention when presenting with achalasia that has eroded the esophageal wall enough to form a megaesophagus. Early and minimally invasive treatments (i.e., medical therapy, endoscopic dilation, and myotomy) are insufficient at this stage, and thus esophageal surgery is required. Among the most common surgical approaches, we must mention esophagectomy sec. McKeown and esophagectomy with interposition of a colic loop sec. Wilkins; however, based on our experience, esophagectomy sec. Ivor-Lewis with intrathoracic anastomosis leads to excellent results and can therefore be considered a valid alternative for treating complex cases. Conclusions: Subtotal esophagectomy sec. Ivor-Lewis with intrathoracic anastomosis is effective in treating achalasia with megaesophagus.

A large and late mediastinal metastasis from a uterine smooth muscle tumour of uncertain malignant potential: A case report.

INTRODUCTION: Smooth muscle tumours of uncertain malignant potential (STUMP) are mesenchymal uterine tumours with a malignant potential found somewhere between that of benign leiomyomas and leiomyosarcomas. Only three cases of STUMP pulmonary metastasis exist in the literature. CASE PRESENTATION: We report the case of a 63 year-old female patient presenting with dysphonia secondary to recurrent laryngeal nerve paralysis due to an enormous mediastinal STUMP metastasis, 14 years after having undergone a total hysterectomy with bilateral salpingo-oophorectomy. A successful left pneumonectomy was performed and the mass weighing 1570 g was histologically confirmed as a STUMP metastasis. DISCUSSION: Only three cases of pulmonary metastasis from STUMP have been reported in the recent literature and no robust information exists about the metastatic nature of STUMP. No cases exist in the literature of a successful pneumonectomy performed for a STUMP metastasis of such large dimensions presenting after many years from the diagnosis of the primary uterine lesion. Physicians should keep in mind that the finding of a smooth muscle tumour in the lung of a woman should promptly raise the suspicion of a metastatic uterine malignancy, even several years after diagnosis of the primary lesion. CONCLUSION: Despite the size, invasiveness and late presentation of the STUMP metastasis, the surgery was successful and the patient no longer requires oxygen therapy.

Double sternal elevation subxiphoid versus uniportal thoracoscopic thymectomy associated with superior clearance for stage I-II thymic epithelial tumors: Subxiphoid thymectomy compared with VATS.

OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of thymectomy through a subxiphoid video-thoracoscopic approach with double elevation of the sternum compared with traditional intercostal uniportal video-assisted thoracic surgery for stage I-II thymic epithelial tumors (using the Masaoka-Koga staging system). METHOD: Patients with thymic tumors underwent resection through intercostal video-assisted thoracic surgery or subxiphoid video-thoracoscopic approach. Only those with pathologically confirmed thymic epithelial tumors were enrolled. Perioperative short-term/long-term outcomes were compared between 2 groups after propensity-score matching. RESULTS: A total of 141 patients diagnosed with thymic epithelial tumors and scheduled for minimally invasive surgery were included. In the intercostal video-assisted thoracic surgery group, the prevalence for conversion to open surgery was higher than in the subxiphoid video-thoracoscopic approach group for stage III thymic tumors (P = .019). After propensity-score matching for 122 patients undergoing video-assisted thoracic surgery, significantly larger resected specimens were found in the subxiphoid video-thoracoscopic approach group compared to the intercostal video-assisted thoracic surgery group (11.7 ± 3.8 vs 7.1 ± 2.7 cm, P < .001). The pain score on the first postoperative day (1.6 ± 0.6 vs 2.0 ± 0.7, P = .011) and the day of hospital discharge (1.2 ± 0.7 vs 1.6 ± 0.6, P = .017) in the subxiphoid video-thoracoscopic approach group were significantly lower. The operation time (168.4 ± 59.3 vs 92.5 ± 46.0 min, P < .001), chest tube drainage time (3.6 ± 1.2 vs 2.9 ± 0.9 days, P = .001), and hospital stay (3.7 ± 1.3 vs 2.9 ± 0.9 days, P = .004) were longer in the subxiphoid video-thoracoscopic approach group, with higher intraoperative blood loss (69.3 ± 61.0 vs 45.6 ± 42.5 mL, P = .045). No significant differences were found in the hospitalization cost, incidence of complications, or 3-year disease-free survival (96% vs 92%, P = .473) between the 2 groups. Four patients with stage III disease in the subxiphoid video-thoracoscopic approach group reached a 3-year disease-free survival of 75%. CONCLUSION: The subxiphoid video-thoracoscopic approach with double elevation of the sternum shows the potential for more extensive clearance of thymic tissue for thymic epithelial tumors compared to intercostal video-assisted thoracic surgery. Its inferior operation time and blood loss could be a trade-off for improved pain control and equivalent hospitalization cost, complications, and 3-year disease-free survival. The subxiphoid video-thoracoscopic approach may offer an advantage treatment for early-stage thymic epithelial tumors and may also be suitable for unexpected advanced thymic tumors identified intraoperatively.

The sternum reconstruction: Present and future perspectives.

Sternectomy is a procedure mainly used for removing tumor masses infiltrating the sternum or treating infections. Moreover, the removal of the sternum involves the additional challenge of performing a functional reconstruction. Fortunately, various approaches have been proposed for improving the operation and outcome of reconstruction, including allograft transplantation, using novel materials, and developing innovative surgical approaches, which promise to enhance the quality of life for the patient. This review will highlight the surgical approaches to sternum reconstruction and the new perspectives in the current literature.

Cancer Stem Cells and Cell Cycle Genes as Independent Predictors of Relapse in Non-small Cell Lung Cancer: Secondary Analysis of a Prospective Study.

PURPOSE: Cancer stem cells (CSCs) are described as resistant to chemotherapy and radiotherapy. It has been shown that CSCs influence disease-free survival in patients undergoing surgery for lung cancer (NCT04634630). We recently described an overexpression of CSCs recurrence-related genes (RG) in lung cancer. This study aims to investigate CSC frequency and RG expression as predictors of disease-free survival in lung cancer. EXPERIMENTAL DESIGN: This secondary analysis of a prospective cohort study involved 22 surgical tumor specimens from 22 patients harboring early (I-II) and locally advanced (IIIA) stages ACL and SCCL. Cell population frequency analysis of ALDHhigh (CSCs) and ALDHlow (cancer cells) was performed on each tumor specimen. In addition, RG expression was assessed for 31 target genes separately in ALDHhigh and ALDHlow populations. CSCs frequency and RG expression were assessed as predictors of disease-free survival by Cox analysis. RESULTS: CSCs frequency and RG expression were independent predictors of disease-free survival. CSC frequency was not related to disease-free survival in early-stage patients (HR = 0.84, 95%CI = 0.53-1.33, P = .454), whereas it was a risk factor for locally advanced-stage patients (HR = 1.22, 95%CI = 1.09-1.35, P = .000). RG expression-if measured in CSCs-was related to a higher risk of recurrence (HR = 1.19, 95%CI = 1.03-1.39, P = .021). The effect of RG expression measured in cancer cells on disease-free survival was lower and was not statistically significant (HR = 1.12, 95%CI = 0.94-1.33, P = .196). CONCLUSIONS: CSCs frequency and RG expression are independent predictors of relapse in lung cancer. Considering these results, CSCs and RG may be considered for both target therapy and prognosis.

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence.

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs' self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/ß-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.