Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases

Background: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Materials and methods: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. Results: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). Conclusions: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series

Relevé: an At-home Ballet Self-learning Interactive System

Benefits from the recent technology advancement, such as physical computing and social media, it has become a global industry trend to provide intelligent exercise and self-learning support in an ‘at-home' environment. However, it is still a design challenge to ensure the safety of users while enhancing their experiences when developing specific ‘at-home' self-training programs which require high-level techniques, such as ballet dancing. This paper introduces Relevé - an interactive self-learning system for ballet with emphasis on various safety issues. Based on the professional knowledge of ballet dancing posture and kinematic movement research, Relevé intends to answer the needs of ballet dancing home-based self-teaching activities through online courses. The design has been based mainly on the methodologies of tangible interaction design

Risonanza Magnetica spettroscopica della mammella: caratterizzazione fisica del sistema per la quantificazione di colina e altri metaboliti

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MR Spectroscopy of the Breast at 3T: An Initial Clinical Experience

PURPOSE To report on an initial experience on breast MR spectroscopy (MRS) at 3T. The study was aimed at characterizing the feasibility of single-voxel choline detection at 3T in suspected malignant breast lesions. METHOD AND MATERIALS 22 patients (24 lesions, range 0.065-8.18cm3, mean 1.93cm3) were enrolled in the study (32-77yrs, mean 57yrs). All patients had suspicious findings on mammography or sonography of the breast, confirmed by cytology and/or micro-biopsy. Single-voxel MRS was performed by means of a Philips Achieva STx 3.0T scanner. Iterative shimming was restricted to the region of interest (ROI) used for spectroscopy (0.512-8.0 cm3, mean 1.097 cm3). The ROI was centred on the lesion, except in cases where a central necrotic area was observed. The spectroscopic sequence used TE=100ms, TR=2000ms, 128 samples, water (window 100Hz) and fat (SPAIR, window 80Hz) suppression. When possible, spectroscopy was performed before contrast agent injection and repeated thereafter. Pre-saturation was used to suppress signal from nearby regions. The local field homogeneity was evaluated by means of the FWHM of the unsuppressed water peak. A threshold was placed at 50Hz, above which spectroscopy was not performed due to insufficient field homogeneity. Total choline was estimated by means of the signal-to-noise ratio of the peak at 3.2ppm. RESULTS MRS was feasible in 54.2% of the lesions (13/24, water peak FWHM 15-44Hz, mean 29Hz). For the other 11 lesions the FWHM of the unsuppressed water peak exceeded 50Hz (57-103Hz, mean 70.3Hz). Of the 13 feasible, 10 lesions showed choline (SNR 3.2-16.6, mean 7.5) while 3 lesions showed no detectable choline. In 2 cases no choline was detected in the central, necrotic region while a clear signal was present at the periphery of the lesion (SNR 5.1-5.4). In 2 cases the cho signal was disrupted after contrast injection. CONCLUSION High-field MR spectroscopy is expected to improve the signal-to-noise ratio of the investigated metabolites (choline in this study), however field homogeneity is more difficult to achieve compared to 1.5T applications. The measured SNR confirmed the expected improvement, but further research is warranted to increase the fraction of cases for which high-field MRS is feasible. CLINICAL RELEVANCE/APPLICATION MRS at 3T could improve the specificity of breast MR, however the possible correlation between total choline concentration and malignancy needs further investigation

Describing the health behaviours of future nurses: A cross-sectional study among Italian nursing students

Academic environments may influence the achievement of healthy behaviors in nursing students. However, the lifestyles among Italian nursing students have been poorly investigated. Therefore, the aim of this study was to describe the health behaviours of Italian undergraduate nursing students. A monocentric, cross-sectional, study design was performed. The study was conducted in an undergraduate nursing course in the north of Italy (University of Pavia). Data were collected through the list of freshmen in nursing in March 2018 (i.e. first years of the undergraduate program) using an online survey and a purposive sampling, where 134 nursing students were enrolled. The results highlighted that the nursing students observed a varied and balanced alimentation. The most problematic areas are referred to the physical activity and the smoking habits. Future research should frame the trajectory of the undergraduate nursing students over the overall education path, also promoting and testing strategies to address the observed issues, such as limited physical activities and smoking habits. (www.actabiomedica.it)

Imaging of the Internal Anal Sphincter: Study of Healthy Subject: Review Article

Introduction: The internal anal sphincter is a smooth muscle that works with other muscles to control defecation. The identification of morphological changes, defects or the precise definition of the level of tumor infiltration of muscle have significant importance in clinical practice. For these reasons the evaluation of shape and volume of muscle in healthy subjects has been studied for many years. The main used imaging techniques are the anal endosonografy, the endoanal coil magnetic resonance imaging and the phase-array coil magnetic resonance. The small size of muscle, the high irregularity in shape, the variability associated with factors such as age and sex, the use of different imaging techniques, including non-invasive ones, and the lack of a standardized method of measurement, can make difficult the correct comparison of the results. In this chapter we will discuss the results reported in the literature concerning the evaluation of muscle in healthy subjects and the advantages and disadvantages of different methods adopted. Normal IAS Variations: Age-related variations:the thickening of the muscle associated to aging is particularly noticeable when the measurements is performed with the EAU and MR with endoanal coil. Sex-related variations: The characterization of the shape of the muscle in relation to sex appears to be controversial with all methods. The only common result is the greater length of the anterior quadrant in males when measured with the EAU. Variations related to other factors: In a study of nulliparous women with the EAU, it is reported a positive correlation between the thickness, measured in the mid anal canal, and BMI. By contrast, in a similar study carried out with MRI without the introduction of endoanal coil the average thickness of the muscle does not appear to be correlated with BMI. The thickness of the IAS in relation to height appears to increase with both methods of MR. Conclusion: The MRI allows a better visualization of the entirety of the pelvic perineal floor compared to EAU, which is extremely effective in imaging the IAS. Even the lower cost and facility and speed of EAU are the basis of most of the research with anal endosonografy. Normal range have been specifically formulated in only a few works for thickness and length. We believe that new studies and a process of standardization of methods of measurement could provide significant advances in the study of muscle either in a state of normality or pathology

The Use of Novel Model-based Iterative Reconstruction (MBIR) Technique in Ultra-Low Dose CT Scanning in Clinical Practice \u2013 A Preliminary Study in 30 Patients

PURPOSE To compare image quality on computed tomographic (CT) images acquired with adaptive statistical iterative reconstruction (ASIR) and novel model-based iterative reconstruction (MBIR) techniques in the context of oncological surveillance using ultra-low dose scanning parameters. METHOD AND MATERIALS 30 patients scheduled for standard of care CT chest/abdomen/pelvis were scanned using ASIR reconstruction and in addition were scanned at 2 pre-selected ultra-low dose scans (using noise index of 60 and 70) with images reconstructed using MBIR. Objective and subjective image qualities were compared. Effective doses for each scans were recorded. Quantitative data such as objective image noise and mean attenuation were analyzed by comparing standard deviations, 95% confidence interval and calculating percentage difference. Mean image noise values and attenuation values were compared between different reconstruction algorithms using ANOVA. The interobserver variation and percentage agreement between the two radiologists for each of the assessed subjective image quality and lesion assessment parameters were estimated by using weighted k-statistics. Kruskal-Wallis rank sum test was used to test for equality of median scores among all subjective parameters RESULTS Objective image analysis supports significant noise reduction with low dose scans using MBIR technique (p<0.05). There was no significant change in the mean CT numbers between different reconstructions (p>0.05). There was no significant difference between subjective image quality of ultra-low dose MBIR scan compared with standard dose scan using ASIR (p>0.05). Dose recorded were substantially lower for low dose MBIR protocol (up to 75% reduction compared with ASIR). Average effective doses were 8.5mSv, 3.8mSv and 2.4mSv for standard scan NI33, NI60 and NI70 respectively. CONCLUSION MBIR shows superior reduction in noise and improved image quality and most importantly substantial dose reduction can be achieved by increasing the noise index parameters as tested in this study. This is a preliminary study, and part of a much larger study of which the results will be available in full at the RSNA 2012. CLINICAL RELEVANCE/APPLICATION To combat against increase use of CT and concerns associated with radiation, MBIR offers another tool in the radiology armoury offering substantial dose reduction without affecting image quality

Assessment of Image Quality vs Dose Using an Iterative Reconstruction Algorithm in Multislice CT

PURPOSE To assess image quality and patient dose obtained in multi slice CT studies by means of a standard Filtered Backprojection algorithm (FBP) versus a new type of iterative algorithm called iDose4 METHOD AND MATERIALS Various scans on a Catphan600 phantom (The Phantom Laboratory) were performed with a Brilliance iCT-256 scanner (Philips Healthcare) varying reconstruction algorithm (FBP and iDose4 with six different levels), kernel (B-D-YB), and dose. Image quality has been compared through the following figures of merit: signal-to-noise ratio (SNR) for low-contrast resolution and MTF-50 for high-contrast resolution. Images were analysed with IQworks. Dose was varied through the mAs/slice mean value set to scan the phantom. The fixed scan parameters used for all the studies were: HV=120kVp, FOV=250mm, pitch=0.993, slice thickness=2.5mm, rotation time=0.75s, matrix size=512x512. 188 patients were scanned according to an iDose4 level 3 protocol (30% dose reduction). Five radiologists performed image quality analysis with a 5 point grading scale (1 worst; 5 excellent) RESULTS With kernel B and 78mAs/slice the following SNR values have been measured: FBP 1.48, iDose4 (levels 1 to 6) 1.62, 1.70, 1.82, 1.98, 2.28, 2.54; for MTF-50 results were: FBP 3.5 lp/cm, iDose4 (levels 1 to 6) 3.4 to 3.5 lp/cm . With FBP (kernel B) and mAs/slice ranging from 78 to 156 results for SNR were: 1.48-2.12 (R2=0.998), and for MTF-50: 3.4-3.7 lp/cm. Equivalent values of SNR (1.81) and MTF-50 (3.5 lp/cm) were obtained with iDose4 level 3-kernel B-78mAs/slice and with FBP-kernel B-117mAs/slice. MTF-50 as a function of the kernel varied from 3.5lp/cm (B) to 6.2lp/cm (YB), almost independently from dose and reconstruction algorithm. Quality image was 5 level in 66,5% of 188 patient examinations and not inferior to 3 level CONCLUSION Phantom assessments showed that the use of the iDose4 algorithm compared to FBP allows SNR to increase up to 70% at equal patient dose and permits to reach a 33% patient dose reduction at equal values of SNR and MTF-50, SNR being the limiting factor. CLINICAL RELEVANCE/APPLICATION 30% dose reduction not compromise image quality. Higher dose reductions seem to be achievable, possibly up to 70%, if high-contrast resolution is the most critical factor (e.g. vascular studies

Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma

Background: Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. Methods: Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. Results: The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. Conclusion: Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy

External validation of COMPASS and BIOSCOPE prognostic scores in colorectal peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)

Introduction: The selection of patients undergoing cytoreductive- surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. BIOSCOPE and COMPASS are prognostic scores designed to stratify survival into four classes according to clinical and pathological features. The purpose of this study is to analyze the prognostic role of these scores using a large cohort of patients as an external reference. Methods: Overall survival analysis was performed using Log-Rank and Kaplan-Meier curves for each score. The probability of survival at 12, 36, and 60 months was tested using receiver operating characteristic (ROC) curves to determine sensitivity and specificity. Results: From the validation cohort of 437 patients, the analysis included 410 patients in the COMPASS group and 364 patients in the BIOSCOPE group (100% data completeness). We observed a different patient distribution between classes (high-risk for BIOSCOPE compared to COMPASS, p = 0.0001). Nevertheless, both COMPASS and BIOSCOPE effectively stratified overall survival (Log-Rank, p = 0.0001 in both cases), with a lack of discrimination between COMPASS classes II and III (p = n.s.). COMPASS at 12 m and BIOSCOPE at 60 m showed the best performance in terms of survival prediction (AUC of 0.82 and 0.81). The specificity of the two tests is good (median 81.3%), whereas sensibility is quite low (median 64.2%). Conclusion: Following external validation in a large population of patients with CRC-PM who are eligible for surgery, the COMPASS and BIOSCOPE scores exhibit high inter-test variability but effectively stratify cancer-related mortality risk. While the quality of the scores is similar, BIOSCOPE shows better inter-tier differentiation, suggesting that tumor molecular classification could improve test discrimination capability. More powerful stratification scores with the inclusion of novel predictors are needed