CLUSTER ANALYSIS IDENTIFIES VARIABLES RELATED TO PROGNOSIS OF BREAST CANCER DISEASE

This work presents a cluster analysis approach aiming to determine distinct groups based on clinicopathological data from patients with breast cancer (BC). For this purpose, the clinical variables were considered: age at diagnosis, weight, height, lymph nodal invasion (LN), tumor-node-metastasis (TNM) staging and body mass index (BMI). Ward's hierarchical clustering algorithm was used to form specific groups. Based on this, BC patients were separated into four groups. The Kruskal-Wallis test was performed to assess the differences among the clusters. The intensity of the influence of variables on the prognosis of BC was also evaluated by calculating the Spearman's correlation. Positive correlations were obtained between weight and BMI, TNM and LN invasion in all analyzes. Negative correlations between BMI and height were obtained in some of the analyzes. Finally, a new correlation was obtained, based on this approach, between weight and TNM, demonstrating that the trophic-adipose status of BC patients can be directly related to disease staging.

Treatment Outside the Recommended Guidelines for Retinopathy of Prematurity (ROP): Prevalence, Characteristics, and Issues

This study aims to assess the prevalence and characteristics of preterm infants with retinopathy of prematurity (ROP) treated outside the recommended guidelines. In this retrospective monocentric cohort, we included all premature children treated in our department for ROP by laser photoablation or anti-VEGF intravitreal injection. The main outcome was treatment of both eyes for ROP less severe than pre-threshold type 1, treated outside ETROP guidelines. A total of 114 children received treatment for ROP in our department, among whom 32 (28.1%) children received treatment for indications outside the ETROP guidelines for both eyes. The indications outside the guidelines were persistent stage 2 or 3 ROP that showed no evidence of regression after 41 weeks of corrected gestational age (11 children; 34.4%), pre-plus stage (11; 34.4%), difficulties in disease staging (7; 21.9%), type 2 ROP with plus disease (2; 6.2 %), and treatment due to logistical difficulties (1; 3.1%; hospitalized in neonatal units hundreds of miles away from our department, with no fundus examination possible in the neonatal unit). To resume, in our cohort, 28.1% of children received treatment for ROP less severe than pre-threshold type 1 both eyes. The main indications for off-label treatment were the persistence of active ROP during follow-up and the presence of pre-plus-stage disease. Our data suggest the need to update ROP treatment criteria to reflect real-life practices. Additional studies are required in order to evaluate the long-term benefits and side effects of treatments outside the recommended indications, and to establish revised treatment guidelines.

A Comparative Study of Serum Angiogenic Biomarkers in Cirrhosis and Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. Its pathogenesis varies according to the underlying etiological factors, although in most cases it develops from liver cirrhosis. The disease progression is accompanied by pathological angiogenesis, which is a prerequisite that favors the development of HCC. Aims: This study aims at contributing to our understanding of the role of angiogenic factors in the progression of liver disease. For this purpose, we evaluate the clinical significance of serum angiogenic markers (VEGF, Ang-1, Ang-2, the angiopoietin receptor Tie1/2, HGF, and PECAM-1) first in cirrhotic and HCC patients separately, and then comparing cirrhotic patients with and without HCC. Materials and Methods: We enrolled 62 patients, out of whom 33 were diagnosed with HCC and 29 with liver cirrhosis without signs of neoplasia. Patients underwent venous blood sampling before and after receiving treatments for the diagnosed disease. Serum markers were evaluated using ELISA assays for Tie1 and the Bio-Plex Multiplex system for the remaining ones. Biomarker levels were investigated as a function of clinical scores for disease staging (MELD and Fibrosis Index, FI). Results: In cirrhotic patients, Ang-1 and Ang-2 correlate with MELD (ρAng-1 = −0.73, p = 2E−5) and FI (ρAng-1 = −0.52, p = 7E−3, ρAng-2 = 0.53, p = 3E−3). A reduction of Ang-2 levels (p = 0.047) and of the Ang-2/Ang-1 ratio (p = 0.031) is observed in cirrhotic patients diagnosed with viral hepatitis after antiviral treatments. In HCC patients, Ang-1 negatively correlates with FI (ρ = −0.63, p = 1E−4), and PECAM-1 positively correlates with MELD (ρ = 0.44, p = 0.01). A significant Ang-1 reduction was observed in deceased patients during the study compared to ones who survived (p = 0.01). In HCC patients, VEGF levels were increased after tumor treatment (p = 0.037). Notably, HGF levels in cirrhotic patients with HCC are significantly raised (p = 0.017) compared to that in those without HCC. Conclusions: Our results suggest that serum angiogenic markers, with emphasis on Ang-1/2, can contribute to the development of quantitative tools for liver disease staging and therapy monitoring. The comparison between cirrhotic patients with and without HCC suggests that HGF levels are potentially useful for monitoring the insurgence of HCC after a cirrhosis diagnosis. High Ang-1 levels in HCC patients appear to have a protective role as well as prognostic significance.

P-OGC45 Could lymphatic, vascular or perineural invasion status improve clinical staging prior to oesophagectomy?

Background Unimodal treatment of oesophagogastric cancer (OGC) with surgery only is currently reserved for patients with early disease. Presence of vascular (VI), perineural (PNI) or lymphatic vessel invasion (LI) in pathological samples have been shown to be negative prognostic indicators of survival. These factors have been found to be associated with more advanced disease. Staging of OGC has limitations and in neoadjuvant naive populations it has been shown to be imperfect. It is unknown whether VI, PNI or LI could play any role during the staging process. Methods Patients with early disease (cT2 or less and cN0) who underwent unimodal treatment of their oesophageal or junctional cancer with oesophagectomy between 2010 and 2019 in a single centre were included in this study. Therelationship between presence of LI, VI and PNI on pathological samples with incorrect staging/upstaging indicating locally advanced disease (defined as pT3+ or pN+) was studied using logistic regression model. Results There were 128 patients included. 26 patients (20%) were upstaged to pT3+ or pN+. LI, VI and PNI were present in 18%, 11% and 8% respectively. The presence of LI and clinical T stage were independently predictive of incorrect staging/upstaging in multivariable logistic regression analysis. LI (OR 12.5 95%CI 3.7-42.8, p < 0.001) and cT2 (OR 5.9 95%CI 1.5-23.2, p = 0.01). Conclusions These results indicate that the presence of LI from pathological samples is a strong independent prognostic factor of incorrect staging which would normally favour neoadjuvant treatment. The presence of LI suggests aggressive disease. Further studies should concentrate on the possibility of obtaining LI status from preoperative biopsies or endoscopic mucosal resection samples. This staging information could play an important role in deciding whether neoadjuvant therapy is indicated in patients staged as early disease.

Intra- and inter-observer reproducibility of r-ASRM endometriosis classification system and its components, using edited videotaped laparoscopic procedures

Several classification systems have been proposed for endometriosis but the search for the ideal system is ongoing. While the most commonly used system has historically been r-ASRM, this system is not fit for purpose, particularly for deep endometriosis. In order to explore strategies to devise a new system and learn from problems with the existing ones, this study was designed to assess the reproducibility of each component in r-ASRM and its total score using videotaped laparoscopic procedures. Two surgeons independently scored 64 edited videos of laparoscopic endometriosis procedure, twice. Using the Kappa statistic, the agreement of the scores given was analyzed. r-ASRM showed a moderate inter-observer agreement (ƙ = 0.503) and good intra-observer agreement (ƙ = 0.774 and 0.682 for scorer 1 and 2 respectively) for overall disease staging. The agreement for each component of the system, however, was highly variable. The least agreement was observed for the peritoneum with ƙ = 0.157 and ƙ = 0.362 respectively for inter-observer and intra-observer. The lowest intra-observer agreement was seen for cul-de-sac for scorer 2 (ƙ = 0.382). Whilst the overall rASRM shows acceptable agreement between two scorers, this agreement seems to be the product of inconsistent scoring for each component.

Recommendations to Optimize the Use of Volumetric MRI in Huntington's Disease Clinical Trials

Volumetric magnetic resonance imaging (vMRI) has been widely studied in Huntington's disease (HD) and is commonly used to assess treatment effects on brain atrophy in interventional trials. Global and regional trajectories of brain atrophy in HD, with early involvement of striatal regions, are becoming increasingly understood. However, there remains heterogeneity in the methods used and a lack of widely-accessible multisite, longitudinal, normative datasets in HD. Consensus for standardized practices for data acquisition, analysis, sharing, and reporting will strengthen the interpretation of vMRI results and facilitate their adoption as part of a pathobiological disease staging system. The Huntington's Disease Regulatory Science Consortium (HD-RSC) currently comprises 37 member organizations and is dedicated to building a regulatory science strategy to expedite the approval of HD therapeutics. Here, we propose four recommendations to address vMRI standardization in HD research: (1) a checklist of standardized practices for the use of vMRI in clinical research and for reporting results; (2) targeted research projects to evaluate advanced vMRI methodologies in HD; (3) the definition of standard MRI-based anatomical boundaries for key brain structures in HD, plus the creation of a standard reference dataset to benchmark vMRI data analysis methods; and (4) broad access to raw images and derived data from both observational studies and interventional trials, coded to protect participant identity. In concert, these recommendations will enable a better understanding of disease progression and increase confidence in the use of vMRI for drug development.

Denosumab-related osteonecrosis of the external auditory canal—benefit of the early surgical management

Background: Antiresorptive drugs are widely used to reduce bone mineral loss in patients with osteoporosis and to prevent skeletal-related events in patients with metastatic cancers and multiple myeloma (MM). Both the bisphosphonates (BP) and denosumab typically used in this indication were shown to be effective and relatively safe. Obviously, this medication could have some adverse effects; one of them is osteonecrosis of the external auditory canal. Only sporadic cases of external auditory canal osteonecrosis have been published yet. Here, we provide a case of denosumab-related osteonecrosis of the external auditory canal successfully treated surgically in the early stage of the disease. Case report: A 68-year-old patient with breast cancer underwent comprehensive oncological treatment, including denosumab administration. She was diagnosed with osteonecroses in the jaw and ear canal. The necrotic bones in both regions were resected with primary wound closure. Both affected sites healed well with no signs of necrosis recurrence. Conclusions: Osteonecrosis of the external auditory canal is a rare but probably underdiagnosed complication of antiresorptive medication. It has a negative impact on patient quality of life if left untreated. Early surgical treatment appears to be effective. The authors highlight several similarities with medication-related osteonecrosis of the jaw. Therefore, an analogous disease staging and treatment rationale is suggested.

Menstruation Dysregulation and Endometriosis Development

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.

MRI versus CT and PET/CT in the Preoperative Assessment of Hodgkin and Non-Hodgkin Lymphomas

(1) Background: The purpose of this study is to retrospectively compare CT, MRI, and PET/CT in detecting lymphadenopathies and extra-nodal lesions in lymphoma and in disease staging. (2) Methods: Inclusion criteria were the availability of TB (Total Body) CT and/or PET/CT performed before treatment; MRI performed no later than 2 weeks after TBCT; histological confirmation of lymphoma; clinical-diagnostic follow-up. Using these criteria, we included 64/353 patients with TBCT and MRI performed at our hospital; 20/64 had PET/CT performed in other hospitals. Histology and follow-up were gold standard. (3) Results: The sensitivity, specificity, and accuracy in lymph nodes detection was 84.5%, 94.4%, and 91% for CT and 95%, 98.9%, and 95.6% for MRI. High agreement was observed between CT and MRI regarding the number and size of positive lymph nodes and for disease staging. MRI identified eight more extra-nodal lesions than CT. In the subgroup of 20 patients, PET/CT did not show a significant superiority in sensitivity, specificity, accuracy, and staging ability than CT and MRI. (4) Conclusions: Our study demonstrates a mild superiority of MRI over CT in lymphoma staging. Although PET/CT remains the reference standard, MRI demonstrated a similar diagnostic accuracy, with the added value of being radiation-free.