ABSTRACT
The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 ('6C' group) or 12 ('12C' group) cycles of temozolomide were collected between 2012 and 2022. A total of 45 patients were included in the 6C group and 42 patients were included in the 12C group. Data on isocitrate dehydrogenase mutation and methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also collected. The 12C group exhibited statistically significantly improved overall survival [OS; 22.8 vs. 17.5 months; hazard ratio (HR), 0.47; 95% CI, 0.30-0.73; P=0.001] and progression-free survival (15.3 vs. 9 months; HR, 0.39; 95% CI, 0.25-0.62; P=0.001). However, in the subgroup analysis according to MGMT status, OS in the 12C group was significantly superior to OS in the 6C group only in the MGMT unmethylated tumors. The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles.
ABSTRACT
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-ß signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-ß signals through SMAD proteins, which are intracellular molecules that transmit TGF-ß signals from the cell membrane to the nucleus. Alterations in the TGF-ß pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-ß signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-ß influences metastasis development. TGF-ß promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-ß affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-ß in mCRC patients, aiming to identify new therapeutic options.
Subject(s)
Colorectal Neoplasms , Signal Transduction , Transforming Growth Factor beta , Tumor Microenvironment , Humans , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Transforming Growth Factor beta/metabolism , Epithelial-Mesenchymal Transition , Animals , Neovascularization, Pathologic/metabolismABSTRACT
INTRODUCTION: Benign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis. MATERIALS AND METHODS: The procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o'clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure. RESULT: We conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of 'Luigi Vanvitelli' of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis. CONCLUSION: Our study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.
Subject(s)
Bronchoscopy , Tracheal Stenosis , Humans , Bronchoscopy/methods , Tracheal Stenosis/surgery , Tracheal Stenosis/etiology , Constriction, Pathologic/complications , Retrospective Studies , EndoscopyABSTRACT
BACKGROUND: Video-assisted thoracoscopic surgery (VATS) resection of deep-seated lung nodules smaller than 1 cm is extremely challenging. Several methods have been proposed to overcome this limitation but with not neglectable complications. Intraoperative lung ultrasound (ILU) is the latest minimally invasive proposed technique. The aim of the current study was to analyze the accuracy and efficacy of ILU associated with VATS to visualize solitary and deep-seated pulmonary nodules smaller than 1 cm. METHODS: Patients with subcentimetric solitary and deep-seated pulmonary nodules were included in this retrospective study from November 2020 to December 2022. Patients who received VATS aided with ILU were considered as group A and patients who received conventional VATS as group B (control group). The rate of nodule identification and the time for localization with VATS alone and with VATS aided with ILU in each group were analyzed. RESULTS: A total of 43 patients received VATS aided with ILU (group A) and 31 patients received conventional VATS (group B). Mean operative time was lower in group A (p < 0.05). In group A all the nodules were correctly identified, while in group B in one case the localization failed. The time to identify the lesion was lower in group A (7.1 ± 2.2 vs. 13.8 ± 4.6; p < 0.05). During hospitalization three patients (6.5%; p < 0.05) in group B presented air leaks that were conservatively managed. CONCLUSION: Intracavitary VATS-US is a reliable, feasible, real-time and effective method of localization of parenchymal lung nodules during selected wedge resection procedures.
Subject(s)
Lung Neoplasms , Multiple Pulmonary Nodules , Solitary Pulmonary Nodule , Humans , Retrospective Studies , Thoracic Surgery, Video-Assisted/methods , Lung Neoplasms/surgery , Solitary Pulmonary Nodule/surgery , Lung , Multiple Pulmonary Nodules/surgeryABSTRACT
RAF family proteins are serine-threonine kinases that play a central role in the MAPK pathway which is involved in embryogenesis, cell differentiation, cell proliferation and death. Deregulation of this pathway is found in up to 30% of all human cancers and BRAF mutations can be identified in 1.5-3.5% of NSCLC patients. Following the positive results obtained through the combination of BRAF and MEK inhibitors in BRAF-mutant melanoma, the same combination was prospectively assessed in BRAF-mutant NSCLC. In cohort B of the BRF113928 trial, 57 pretreated NSCLC patients were treated with dabrafenib plus trametinib: an ORR of 68.4%, a disease control rate of 80.7%, a median PFS of 10.2 months and a median OS of 18.2 months were observed. Similar results were reported in the first-line setting (cohort C), with an ORR of 63.9%, a DCR of 75% and a median PFS and OS of 10.2 and 17.3 months, respectively. The combination was well tolerated: the main adverse events were pyrexia (64%), nausea (56%), diarrhoea (56%), fatigue (36%), oedema (36%) and vomiting (33%). These positive results led to the approval of the combination of dabrafenib and trametinib for the treatment of BRAF V600E metastatic NSCLC patients regardless of previous therapy. Ongoing research should better define the role of new generation RAF inhibitors for patients with acquired resistance, the activity of chemo-immunotherapy or the combination of TKIs with chemotherapy or with immunotherapy in patients with BRAF-mutated cancers.