Large randomized trials have demonstrated that lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces LC mortality in heavy smokers. We previously showed in the MILD screening ...trial that the combination of a prespecified circulating microRNA (miRNA) signature classifier (MSC) and LDCT improves the accuracy of LDCT alone. The primary aim of the prospective BioMILD study was to assess the additional value of the blood MSC assay at the time of baseline LDCT with the goal of personalizing LC screening intervals.
The study enrolled 4119 volunteers from January 2013 to March 2016, with a median follow-up of 5.3 years. Baseline LDCT and miRNAs stratified participants into four groups: CT−/MSC− (n = 2664; 64.7%); CT−/MSC+ (n = 800; 19.4%); CT+/MSC− (n = 446; 10.8%); and CT+/MSC+ (n = 209; 5.1%). As per the protocol, those in the CT−/MSC− and CT−/MSC+ groups were allocated to LDCT repeat at 3-year and 1-year intervals; CT+ participants were allocated for 1-year or earlier intervals on the basis of LDCT features independent of MSC results.
CT+ participants had a 15.8-fold higher 4-year LC incidence than CT− participants (95% confidence interval 10.34-24.05), and MSC+ participants had a 2.0-fold higher 4-year LC incidence than MSC− participants (95% confidence interval 1.40-2.90); there was no evidence that the MSC effect differed between CT+ and CT− participants. LC incidence at 4 years was 0.8% in CT−/MSC−, 1.1% in CT−/MSC+, 10.8% in CT+/MSC−, and 20.1% in CT+/MSC+ participants. LC mortality rates at 5 years in the four risk groups were 0.5 in CT−/MSC−, 1.5 in CT−/MSC+, 4.2 in CT+/MSC−, and 10.1 in CT+/MSC+.
The combined use of LDCT and blood miRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals.
•Baseline LDCT and blood microRNAs define individual lung cancer risk profiles.•Targeted LDCT intervals reduce unnecessary repeat LDCT.•A biomarker-based risk test showed a major added value for CT+ participants.
We evaluated the efficacy of the α1-adrenergic antagonist tamsulosin for conservative expulsive therapy in patients with ureteral colic due to juxtavesical stones.
A total of 60 consecutive ...symptomatic patients with stones located in the juxtavesical tract of the ureter were randomly divided into group 1—30 who received oral floroglucine-trimetossibenzene 3 times daily and group 2—30 who received 0.4 mg tamsulosin daily. The 2 groups received 30 mg deflazacort daily for 10 days plus cotrimoxazole 2 times daily for 8 days and 75 mg diclofenac injected intramuscularly on demand. Ultrasound followup and medical visits were performed weekly for 4 weeks. Stone passage rate and time, analgesic use, hospitalization and endoscopical intervention were evaluated. Statistical analysis was performed using the Student t test.
The stone expulsion rate was 70% for group 1 and 100% for group 2. Mean stone size was 5.8 and 6.7 mm, respectively (p = 0.001). Mean expulsion time was 111.1 hours for group 1 and 65.7 hours for group 2 (p = 0.020). The mean number of diclofenac injections was 2.83 for group 1 and 0.13 for group 2 (p <0.0001). Ten group 1 patients were hospitalized, of whom 9 underwent ureteroscopy, compared with none in group 2 (p <0.0001 and 0.001, respectively).
Tamsulosin used as a spasmolytic drug during renal colic due to juxtavesical calculi increased the stone expulsion rate and decreased expulsion time, the need for hospitalization and endoscopic procedures, and provided particularly good control of colic pain.
The comparison between chest x-ray (CXR) and computed tomography (CT) images is commonly required in clinical practice to assess the evolution of chest pathological manifestations. Intrinsic ...differences between the two techniques, however, limit reader confidence in such a comparison. CT average intensity projection (AIP) reconstruction allows obtaining “synthetic” CXR (s-CXR) images, which are thought to have the potential to increase the accuracy of comparison between CXR and CT imaging. We aim at assessing the diagnostic performance of s-CXR imaging in detecting common pleuro-parenchymal abnormalities.
142 patients who underwent chest CT examination and CXR within 24 hours were enrolled. CT was the standard of reference. Both conventional CXR (c-CXR) and s-CXR images were retrospectively reviewed for the presence of consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion by 3 readers in two separate sessions. Sensitivity, specificity, accuracy and their 95% confidence interval were calculated for each reader and setting and tested by McNemar test. Inter-observer agreement was tested by Cohen's K test and its 95%CI.
Overall, s-CXR sensitivity ranged 45–67% for consolidation, 12–28% for nodule/mass, 17–33% for linear opacities, 2–61% for reticular opacities, and 33–58% for pleural effusion; specificity 65–83%, 83–94%, 94–98%, 93–100% and 79–86%; accuracy 66–68%, 74–79%, 89–91%, 61–65% and 68–72%, respectively. K values ranged 0.38–0.50, 0.05–0.25, -0.05–0.11, -0.01–0.15, and 0.40–0.66 for consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion, respectively.
S-CXR images, reconstructed with AIP technique, can be compared with conventional images in clinical practice and for educational purposes.
•CT average intensity projection reconstruction allows obtaining “synthetic” CXR.•s-CXR yielded a diagnostic performance similar to conventional CXR.•s-CXR can be compared with conventional CXR images in clinical practice.
The European Society of Radiology (ESR) and European Respiratory Society (ERS) published their joint statement paper on lung cancer screening (LCS), on 12 February 2020. This document joins and ...completes previous recommendations on LCS with specific emphasis on the analysis of issues encountered in the practical implementation of LCS in the community. Major milestones to enable the most efficient and equal dissemination of LCS are recognised as engagement of all stakeholders (e.g. candidate/participant, general practitioners, up to the specialised LCS facility), quality assurance, and primary prevention in the form of provision of counselling for smoking cessation.
To assess the clinical efficacy of the addition of a corticosteroid drug to tamsulosin in the medical-expulsive therapy of distal ureterolithiasis.
Sixty consecutive patients with a symptomatic ...distal ureteral stone were included in our study and randomized to one of two home treatment groups. Group 1 patients (n = 30) received tamsulosin (0.4 mg daily), and group 2 patients (n = 30) were treated with a corticosteroid drug (deflazacort, 30 mg daily) plus tamsulosin. The treatment duration was until stone expulsion or 28 days, whichever came first. The primary endpoint of the study was the stone expulsion rate. The secondary endpoints were the expulsion time; use of analgesics; number of emergency room admissions, hospitalizations, and workdays lost; drug side effects; and quality of life of the patients (EuroQol questionnaire, EQ-5D) during treatment.
The two groups had a similar expulsion rate (90% for group 1 and 96.7% for group 2;
P = 0.612), but the expulsion time was significantly reduced in group 2 patients (
P = 0.036). During the treatment period, we did not observe significant differences between the two groups in the number of emergency room visits or hospitalizations, analgesic use, number of workdays lost, or incidence of drug side effects. The quality of life of the patients during therapy, as determined using the EQ-5D, was similar in both groups.
The use of a corticosteroid drug in association with tamsulosin seemed to induce more rapid stone expulsion. In addition, tamsulosin alone as medical-expulsive therapy for distal ureteral calculi had excellent expulsive effectiveness.
Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of ...choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup.
A total of 48 patients with a mean age ± SD of 58.2 ± 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 ± 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186).
Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm
2) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival.
Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.
Purpose
Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of ...patients who are candidate to radical prostatectomy.
Methods
We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival.
Results
389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small.
Conclusions
Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.
Surgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that ...regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin‐embedded sections, using anti‐5‐methylcytosine (5mc) and anti‐Acetyl‐Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P= 0.033), whereas the percentage of histone acetylation was significantly lower (P= 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.
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