Post-Hypoglycemic hyperglycemia are highly relevant markers for stratification of glycemic variability and partial remission status of pediatric patients with new-onset type 1 diabetes.

AimsTo evaluate whether parameters of post-hypoglycemic hyperglycemia (PHH) correlated with glucose homeostasis during the first year after type 1 diabetes onset and helped to distinguish pediatric patients undergoing partial remission or not.MethodsIn the GLUREDIA (GLUcagon Response to hypoglycemia in children and adolescents with new-onset type 1 DIAbetes) study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual β-cell secretion from children with new-onset type 1 diabetes were analyzed during the first year after disease onset. PHH parameters were calculated using an in-house algorithm. Correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH area under the curve [PHHAUC]) and glycemic homeostasis markers were studied using adjusted mixed-effects models.ResultsPHH parameters were strong markers to differentiate remitters from non-remitters with PHH/Hyperglycemia duration ratio being the most sensitive (ratioConclusionPHH parameters are new minimal-invasive markers to discriminate remitters from non-remitters and evaluate glycemic homeostasis during the first year of type 1 diabetes. PHH parameters may also allow patient-targeted therapeutic management of hypoglycemic episodes

Characterization of Preoperative, Postsurgical, Acute and Chronic Pain in High Risk Breast Cancer Patients

Funding: The Ketorolac in Breast Cancer trial has been supported by the Anticancer Fund, the Belgian Society of Anaesthesia and Resuscitation, the Fondation Saint-Luc, and the Commission du Patrimoine of the Université catholique de Louvain, Cliniques universitaires Saint-Luc. Acknowledgments: Membership of the KBCt Group, Aline van Maanen, Gauthier Bouche, Alain Dekleermaker, Francois P Duhoux, Marc De Kock, Martine Berliere, Pierre Coulie, Jan Decloedt, Jean-Edouard Guillaume, Marc Ledent, Jean-Pascal Machiels, Véronique Mustin, Walter Swinnen, Lionel Vander Essen, and Jean-Christophe Verougstraete.Peer reviewedPublisher PD

Intraoperative ketorolac in high-risk breast cancer patients : A prospective, randomized, placebo-controlled clinical trial

Funding: This work is financed by grants received by PF, in the name of his institution: the Anticancer Fund (no grant number) (www.anticancerfund.org); the Belgian Society of Anaesthesia and Resuscitation (no grant number) (www.sarb.be); the Fondation Saint-Luc (no grant number) (www.uclouvain.be); the Commission du Patrimoine of the Université catholique de Louvain, St-Luc Hospital (exceptional grant, no number) (www.uclouvain.be). None of the funders had any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript except the scientific advise of GB, scientific director of the Anticancer Fund.Peer reviewedPublisher PD

Characterization of Preoperative, Postsurgical, Acute and Chronic Pain in High Risk Breast Cancer Patients

Background: Pain after breast cancer surgery remains largely unexplained and inconsistently quantified. This study aims to describe the perioperative pain patterns in patients with breast cancer, up to two years after surgery. Methods: This is a pre-planned sub-study of the Ketorolac in Breast Cancer (KBC) trial. The KBC trial was a multicentre, prospective, double-blind, placebo-controlled, randomised trial of a single dose of 30 mg of ketorolac just before breast cancer surgery, aiming to test its effect on recurrences. This sub-study focuses only on pain outcomes. From 2013 to 2015, 203 patients were randomised to ketorolac (n = 96) or placebo (n = 107). Structured questionnaires were delivered by telephone after one and two years, exploring the presence, location, permanence, and frequency of pain. Patients’ perceptions of pain were captured by an open-ended question, the responses to which were coded and classified using hierarchical clustering. Results: There was no difference in pain between the ketorolac and the placebo group. The reported incidence of permanent pain was 67% and 45% at one and two years, respectively. The largest category was musculoskeletal pain. Permanent pain was mainly described in patients with musculoskeletal pain. The description of pain changed in most patients during the second postoperative year, i.e., moved from one category to another (no pain, permanent, or non-permanent pain, but also, the localisation). This phenomenon includes patients without pain at one year. Conclusions: Pain is a complex phenomenon, but also a fragile and unstable endpoint. Pain after breast cancer surgery does not necessarily mean breast pain but also musculoskeletal and other pains. The permanence of pain and the pain phenotype can change over time

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology

Background: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. Methods: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m2 at week 1, then 250 mg/m2/week) and Gemcitabine (1 g/m2 on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. Results: Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect =grade 2 was associated with increased PFS (P = 0.05).Conclusion(s): Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy

Dental prevention of maxillo-mandibular osteoradionecrosis: A ten-year retrospective study

INTRODUCTION Osteoradionecrosis (ORN) remains a frequent complication of radiotherapy in head and neck cancer. As ORN management is often complex, it is essential to focus on its prevention, mainly by dental prophylaxis. The objectives of this study were to evaluate a dental preventive approach based on ORN data and to highlight individual risk factors statistically associated with time-to-ORN. MATERIALS AND METHODS A retrospective study (January 2004-December 2013) included 415 patients with head and neck cancer who received radiotherapy in their treatment with at least 50 Grays on maxillo-mandibular bones. Preradiotherapy dental assessment (clinical and radiological) and prevention (with standardized extraction protocol) were performed. RESULTS The ORN rate was 7.5%, with a dental origin in 35.5% of cases, mainly represented by dental infection in exclusive mandibular locations. More than 90% of patients were partially or completely dentate, and more than 70% had poor oral hygiene. Dental extractions were performed in 67.9% of patients before radiotherapy and in 42.9% after radiotherapy. Statistically significant risk factors associated with time-to-ORN were addictions (tobacco and alcohol), diabetes, oropharyngeal tumour location, combination of surgery followed by radiotherapy and post-radiotherapy dental extractions. DISCUSSION AND CONCLUSION Considering that ORN implies severe disabilities and complex management, the rate of 7.5% is unacceptable. A better dental prevention could reduce this rate by one-third. Dental extractions could be systematic in high-dose irradiation mandibular areas in patients presenting with poor oral hygiene and/or statistically significant risk factors for the occurrence of ORN. Moreover, favourable oral condition after radiotherapy should be maintained

Actinomycosis and osteonecrosis of the jaw: Every why hides a why

Osteonecrosis of the jaws (ONJ) is a chronic and challenging disease for most clinicians. Two types of ONJ are described with different etiologies and pathophysiological mechanisms: osteoradionecrosis (ORN) and Medication-Related Osteonecrosis of the Jaws (MRONJ). Actinomyces is a Gram positive, filamentous, facultative and anaerobic bacteria that exists in the normal flora of oral cavity, gastrointestinal tract and female genital tract. It belongs to Actinomycetaceae, Propionibacteriaceae and Bifidobacteriacea species with Actinomyces israelii, Actinomyces rencseriae and Actinomyces naeslundii / viscosus representing more than 75% of them. However, the most common agent found into the oral cavity is Actinomyces israelii. Actinomyces infection causes on the head and neck region a suppurative and granulomatous infectious reaction with abscess formation, tissue fibrosis, and occasionally a soft tissue tumor-like mass. It usually follows a dental disease or a jaw osteomyelitis commonly called the “lumpy jaw syndrome

Prospective validation of an institutional treatment strategy for T1N0M0 glottic carcinoma

Introduction: The aim of this study was to assess the validity of a treatment strategy for T1N0 glottic squamous cell carcinoma. Methods: One hundred and seventeen patients were prospectively treated according to institutional guidelines. using 1) laser microsurgery (L) for exophytic tumor, limited to one vocal cord, without extension to the anterior commissure or the vocal process of the arytenoid cartilage, 2) radiotherapy (RT) for large or infiltrative tumor reaching the anterior commissure or the vocal process of the arytenoid cartilage, poor endoscopic exposure and cT1b or 3) partial laryngectomy (PL) for tumor infiltrating the anterior commissure. Ninety-five patients were treated with RT and 22 with surgery alone (S) [L:19; PL:3]. Results: The 5-year overall survival (OS) and disease-specific survival (DSS) were 81.5% and 97.1% (median follow-up: 73 months), respectively. There was no statistically significant difference in OS or DSS between patients treated with RT or S (logrank test: p ¼ 0.974 and 0.978). The 5-year ultimate local control rate reached 98.3%. The local control rate with larynx preservation was 94.9% with no difference between RT (94.7%) and S (95.5%) (c2: p¼ 0.891). Continued smoking after RT was significantly associated with a lower 5-year OS (77.9% versus 87%), [HR 3.458; p ¼ 0.043 (95%CI 1.010e11.837)]. Conclusions: For patients with T1 glottic carcinoma, and based on our previous studies, these data prospectively confirm the oncologic validity of an institutional treatment strategy. Continued smoking after RT correlated with poor OS

Accuracy of Pancreatic Neuro-Endocrine Tumour Grading by Endoscopic Ultrasound-Fine-Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement.

Introduction: Since the WHO Classification of Tumours of the Digestive System has been published in 2010, resected pancreatic neuroendocrine tumours (pNETs) are graded as grade 1 (G1), grade 2 (G2) or grade 3 (G3) using the Ki67 labelling index (Ki67-LI). Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often used for diagnosis, but few studies have assessed its value for grading. Aims: The aims of this study were to compare the Ki67-LI obtained by cytological grading (cG) with that obtained by histological grading (hG) and to assess (1) the influence of tumour size and the number of counted cells on FNA grading as well as (2) the overall survival (OS) and progression-free survival based on cG. Materials and Methods: EUS-FNA was performed for 102 pNETs (57 resected). cG (200 cells counted) was done on all FNAs. For 29 FNAs, >2,000 cells were counted (14 resected). A comparison was made between hG and cG for the 57 resected patients. Patients were followed up until June 2016. Results: cG was consistent with hG in 39 of 57 patients with a concordance rate of 72% using a Ki67-LI cut-off of 5% for G1/G2. For Ki67-LI absolute values, the correlation was r = 0.443 and increased to r = 0.824 (p 2,000 cells were counted. Twenty-one of 22 pNETs 2 cm. Thirty-eight patients died after 70.5 months of follow-up. OS for the whole cohort was 235 months and differed between cG1 (235 months), cG2 (36.3 months) and cG3 (10.9 months). Conclusion: cG of pNETs is more accurate when tumours measure <2 cm and more cells are counted on FNA. Discrepancies are seen between G2 tumours which are often considered G1 on FNA due to tumour heterogeneity. EUS-FNA is valuable to distinguish between patients with good (cG1) and poor (cG3) prognosis

Low contrast detectability and spatial resolution with model-based Iterative reconstructions of MDCT images: a phantom and cadaveric study.

OBJECTIVES: To compare image quality [low contrast (LC) detectability, noise, contrast-to-noise (CNR) and spatial resolution (SR)] of MDCT images reconstructed with an iterative reconstruction (IR) algorithm and a filtered back projection (FBP) algorithm. METHODS: The experimental study was performed on a 256-slice MDCT. LC detectability, noise, CNR and SR were measured on a Catphan phantom scanned with decreasing doses (48.8 down to 0.7 mGy) and parameters typical of a chest CT examination. Images were reconstructed with FBP and a model-based IR algorithm. Additionally, human chest cadavers were scanned and reconstructed using the same technical parameters. Images were analyzed to illustrate the phantom results. RESULTS: LC detectability and noise were statistically significantly different between the techniques, supporting model-based IR algorithm (p < 0.0001). At low doses, the noise in FBP images only enabled SR measurements of high contrast objects. The superior CNR of model-based IR algorithm enabled lower dose measurements, which showed that SR was dose and contrast dependent. Cadaver images reconstructed with model-based IR illustrated that visibility and delineation of anatomical structure edges could be deteriorated at low doses. CONCLUSION: Model-based IR improved LC detectability and enabled dose reduction. At low dose, SR became dose and contrast dependent. KEY POINTS: • Model- based Iterative Reconstruction improves detectability of low contrast object. • With model- based Iterative Reconstruction, spatial resolution is dose and contrast dependent. • Model-based Iterative Reconstruction algorithms enable improved IQ combined with dose-reduction possibilities. • Improvement of SR and LC detectability on the same IMR data set would reduce reconstructions