40 research outputs found
The role of spiral multidetector dynamic CT in the study of Williams-Campbell syndrome.
No full textWilliams-Campbell syndrome is a cystic bronchiectatic disease secondary to deficiency or defect of cartilaginous plates in the wall of the airways. In the literature, two main forms are suggested: congenital and acquired (post-infectious). The most frequent symptoms are represented by recurrent pulmonary infections from childhood. Multislice spiral dynamic CT has a major role in the study of cystic pulmonary disease and in differentiating Williams-Campbell syndrome from the other causes of cystic bronchiectasis, in which even lung function tests can give deceptive results
Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: a systematic review and meta-analysis
No full textRegorafenib (REG) is an oral multikinase inhibitor used in colorectal cancer,
gastrointestinal stromal tumour and hepatocellular carcinoma. Several adverse events
(AEs) are commonly reported during REG administration, and strategies for managing AEs in
everyday clinical practice include supportive care, dose modifications and, when necessary,
treatment withdrawal. We performed a systematic review and meta-analysis to assess the
schedule treatment modifications of REG associated with AEs across randomized controlled
clinical trials (RCTs
Complete radiological response to first-line regorafenib in a patient with abdominal relapse of BRAF V600E mutated GIST
No full textUp to 13% of KIT and PDGFRA wild-type (WT) gastrointestinal stromal tumours (GIST) harbour a BRAF mutation, mostly involving the exon 15 V600E hot spot. Even if BRAF mutation is recognized as druggable target in other solid tumours, currently advanced BRAF-mutant GIST share the same therapeutical algorithm of KIT/PDGFRA mutants.
We report a complete radiological response in a 51-year-old woman with V600E BRAF-mutated metastatic GIST who was treated with regorafenib (REG) as first-line therapy.
REG represents the standard third-line therapy for advanced GIST patients progressing on or failing to respond to imatinib and sunitinib. However, according to its wide spectrum of action, with MAPK signalling pathway blockade at different levels, metastatic KIT/PDGFRA WT, including BRAF mutants, may benefit from REG upfront in first line
Impressive long-term disease stabilization by nilotinib in two pretreated patients with KIT/PDGFRA wild type metastatic gastrointestinal stromal tumors.
No full textKIT/PDGFRA wild-type (WT) gastrointestinal stromal tumours (GISTs) showed a response rate to imatinib ranging from 0 to 25%. Nilotinib is a new-generation tyrosine kinase inhibitor that has demonstrated clinical activity in pretreated GIST patients. At present, no correlation between nilotinib activity and clinical/pathological/molecular features is available. We report on two WT GIST patients resistant to imatinib and sunitinib, and enrolled in the CAMN107A2201 study who achieved an impressive disease control by nilotinib. Both patients have germ-line mutations in the SDHA gene. In April 2004, a 39-year-old woman presented gastric GIST with multiple liver metastases and was treated with imatinib 400 mg/day, followed by imatinib 800 mg/day and then sunitinib. In August 2007, because of disease progression, she was enrolled in the CAMN107A2201 study and assigned to the nilotinib 800 mg/day arm. In March 2005, a 27-year-old woman started imatinib 600 mg/day and then sunitinib for gastric GIST with multiple liver and lung metastases. In October 2007, because of disease progression, she was enrolled in the CAMN107A2201 study and assigned to the nilotinib 800 mg/day arm. One patient still showed stable disease after 46 months of treatment according to the Response Evaluation Criteria In Solid Tumors, and a partial response after 9 months according to Choi's criteria. The other patient still showed stable disease after 42 months according to Response Evaluation Criteria In Solid Tumors. At present, they continue to receive nilotinib. We report very long-term disease stabilization under nilotinib treatment in two pretreated WT GIST patients. In-vitro studies and clinical analyses are warranted to evaluate a potential correlation between nilotinib activity and WT genotype or other clinical/pathological features
Anti-synthetase syndrome with lung involvement associated with primary biliary cirrhosis: A case report
No full textSummaryWe here report a case of association between primary biliary cirrhosis and anti-synthetase syndrome with exclusive interstitial lung involvement. The patient developed exertional dyspnoea 14 years after being diagnosed with primary biliary cirrhosis. Search for auto-antibodies showed positivity for anti-Jo-1. No clinically evident myositis was present. HRCT scan showed bilateral interstitial pulmonary involvement, and the BAL yielded an alveolar lymphocytosis with low CD4/CD8 ratio. Treatment with systemic corticosteroids led to rapid improvement of the clinico-radiological picture. Although primary biliary cirrhosis had been previously found in association with polymyositis, no previous reports of its association with anti-Jo-1 syndrome with prominent pulmonary involvement are known
A molecular portrait of gastrointestinal stromal tumors: an integrative analysis of gene expression profiling and high-resolution genomic copy number.
No full textIn addition to KIT and PDGFRA mutations, sequential accumulation of other genetic events is involved in the development and progression of gastrointestinal stromal tumors (GISTs). Until recently, the significance of these other alterations has not been thoroughly investigated. We report the first study that integrates gene expression profiling and high-resolution genomic copy number analyses in GIST. Fresh tissue specimens from 25 patients with GIST were collected, and gene expression profiling and high-resolution genomic copy number analyses were performed, using Affymetrix U133Plus and SNP array 6.0. We found that all 21 mutant GIST patients showed both macroscopic cytogenetic alterations and cryptic microdeletions or amplifications, whereas 75% (three of four) of wild-type patients with GIST did not show genomic imbalances. The most frequently observed chromosomal alterations in patients with mutant GIST included 14q complete or partial deletion (17 of 25), 1p deletion (14 of 25) and 22q deletion (10 of 25). Genetic targets of the chromosomal aberrations were selected by integrated analysis of copy number and gene expression data. We detected the involvement of known oncogenes and tumor suppressors including KRAS in chr 12p amplification and KIF1B, PPM1A, NF2 in chr 1p, 14q and 22p deletions, respectively. The genomic segment most frequently altered in mutated samples was the 14q23.1 region, which contains potentially novel tumor suppressors, including DAAM1, RTN1 and DACT1. siRNA-mediated RTN1 downregulation showed evidence for the potential role in GIST pathogenesis. The combination of gene expression profiling and high-resolution genomic copy number analysis offers a detailed molecular portrait of GISTs, providing an essential comprehensive knowledge necessary to guide the discovery of novel target genes involved in tumor development and progression
Spontaneous Evolution of COVID-19 Lung Sequelae: Results from a Double-Step Follow-Up
No full textBackground: Few studies have reported a double-step follow-up of patients after hospitalization for COVID-19. Objectives: We designed an observational double-step follow-up study with a clinical, functional, and radiological evaluation at 2 and 6 months after COVID-19. The primary outcome was to describe symptoms, spirometry, and 6-minute walking test (6MWT) at 2 and 6 months. Secondary outcomes were to identify if the lowest PaO2/FiO2 during hospitalization is related with functional and radiological evolution and to assess the correlation between radiological and functional abnormalities at 6 months. Methods: Symptoms, spirometry, and 6MWT were assessed at 2 and 6 months; arterial blood gas, chest x-ray, and lung ultrasound were performed at 2 months; body plethysmography, diffusing capacity for carbon monoxide (DLCO), and CT scan were performed at 6 months. Results: Sixty-four per cent and 42% of patients reported at least one symptom at 2 and 6 months, respectively. The most common 6-month functional alteration was DLCO impairment (57% of patients). An improvement of FEV1, FVC, and 6MWT was observed between 2 and 6 months (p < 0.001). Patients with PaO2/FiO2 <200 during hospitalization performed worse at 6MWT at 2 and 6 months (p < 0.05) and reported more extended radiological abnormalities at 6 months (p < 0.001) compared with patients with PaO2/FiO2>200. At 6 months, more extended radiological abnormalities were related with worse 6MWT, DLCO, and total lung capacity (p < 0.05). Discussion: DLCO and 6MWT impairment seem to be the functional hallmark of COVID-19 and are related with the severity of acute pneumonia. At 6 months, radiological abnormalities were related to functional impairment
