Molecular Pathogenesis associated with Stomach Stromal Tumour: The Paradigm for Personalized Remedies.

Further research examining effective methods to improve recovery from neurologic deficits in patients with a paraneoplastic neurologic illness is warranted.Small cell lung cancer (SCLC) is a very aggressive, highly lethal, neuroendocrine tumor that constitutes 15% of all lung cancer cases. It is characterized by its rapid disease progression and high relapse rate leading to poor survival for diagnosed patients. Recently, poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as a novel therapeutic strategy for SCLC. Preclinical studies have demonstrated that PARPi possesses cytotoxic activity as a single-agent and in combination with other anti-cancer agents. Predictive biomarkers of response to PARPi, such as SLFN11, have also been described in SCLC. This review aims to summarize the recent preclinical investigations and the relevant clinical trials that evaluate PARPi in SCLC. Here, we highlight the potential role of PARPi in a biomarker-selected manner and in combination with chemotherapy, targeted agents, radiotherapy and immunotherapy.First-line stereotactic radiosurgery (SRS) is now considered the preferred treatment over whole brain radiation therapy (WBRT) for limited brain metastases arising from most tumor histologies. This standard was reached following the consistent results of multiple phase III studies which demonstrated that, despite improved CNS control, the addition of WBRT to SRS does not improve overall survival (OS) and is associated with a reduction in cognitive function. Thus, it may be reasonable to consider the benchmark necessary to favor a paradigm of SRS alone over strategies incorporating WBRT as the demonstration of comparable OS in the context of decreased treatment-related side effects. However, patients with small-cell lung cancer (SCLC) brain metastases were excluded from the landmark trials that established SRS alone for limited brain metastases, largely due to concerns for short-interval CNS progression in SCLC as well the historic role of prophylactic cranial irradiation (PCI) in SCLC in the absence of known brain metastases. As a result, WBRT has remained the standard for SCLC for limited and even solitary brain lesions. With shifting SCLC care patterns including increased MRI surveillance, decreased PCI delivery, and emerging systemic agents, interest in first-line SRS for SCLC is likely to continue to increase over time. Herein we will review the emerging data for first-line SRS in the management of SCLC brain metastases and the potential for its increasing role in the setting of a greater utilization of MRI surveillance and improving systemic therapies.The treatment paradigm for extensive stage small cell lung cancer (ES-SCLC) is evolving. Prophylactic cranial irradiation (PCI) has long been considered a component of standard treatment in patients with extensive stage disease who respond to chemotherapy. However, in the modern era of magnetic resonance imaging, the role of PCI has become an area of controversy following conflicting level I evidence. Due to conflicting data and toxicity concerns, the routine use of PCI has declined. Recent improvements in systemic disease control with the use of immunotherapy and reductions in the toxicity attributable to PCI with hippocampal avoidance and memantine have reignited the discussion. As such, we present here a narrative review of PCI with a focus on historical milestones, randomized data, risk mitigation and future directions.Small cell lung cancer (SCLC) is an aggressive malignancy. Until recently the standard of care for newly diagnosed patients with extensive-stage disease was chemotherapy consisting of etoposide plus a platinum (EP). The median overall survival (OS) was only about 10 months with this systemic therapy. Immune checkpoint inhibitors were first evaluated as second or subsequent line treatments in extensive stage disease and later in combination with EP in the first-line setting. Recently two randomized phase III trials have demonstrated statistically improved OS with addition of a programmed death ligand-1 (PD-L1) inhibitor to EP. As a result, the standard of care for newly diagnosed patients with extensive-stage SCLC has changed for the first time in decades. However, many patients do not derive benefit from the addition of a PD-L1 inhibitor to EP. In this review we discuss first-line trials of chemoimmunotherapy in extensive stage SCLC and summarize data on second and subsequent line treatment with immune checkpoint inhibitors in immunotherapy-naïve patients. Additionally, we discuss potential biomarkers that could be utilized to select for which patients derive benefit from addition of a PD-L1 inhibitor to EP and propose ways to improve on first-line chemoimmunotherapy.Pathology arising from the intrathoracic portion of the trachea (distal trachea), the carina and the main bronchi is usually neoplastic and is mainly treated with surgery. Resection of the intrathoracic portion of the trachea, the carina and the main bronchi for neoplastic lesions does not necessitate lung resection and is traditionally being conducted via open surgery. Video-assisted thoracic surgery (VATS) is witnessing an exponential growth and is the treatment of choice for early-stage non-small cell lung cancer (NSCLC). The experience accumulated over the past two decades along with the introduction of reliable and ergonomic technology, has led to the expansion of its indications. In this article we provide a detailed description of lung sparing distal tracheal, carinal and main bronchi resection for primary neoplasms of the airway, without involvement of the lung, with the uniportal video-assisted technique. The chest is entered through the fourth intercostal space, mid-axillary line. Dissection of the paratracheal space anteriorly, the tracheoesophageal groove posteriorly and the subcarinal space and division of the azygos arch are essential to mobilize the distal trachea and carina. Lateral dissection should be avoided beyond the points of division of the airway, as it may hinder the blood supply to the anastomosis. JQ1 Any tension to the anastomosis should be relieved by release maneuvers. Ventilation is achieved through an endobronchial catheter, inserted into the left main bronchus through which a high-frequency jet ventilation catheter can be also inserted through it. The rationale of applying a minimally invasive technique for the conduction of tracheal and carinal resections, is to exploit its advantages, namely less pain, earlier mobilization and lower morbidity. Uniportal video-assisted resections of the distal trachea, carina and the main bronchi, are safe when conducted by experienced surgical and anesthetic teams.JQ1