Calcium absorption following small bowel resection in man. Evidence for an adaptive response

Seventeen patients who had undergone extensive small bowel resection were studied for calcium absorption (FACa) and plasma vitamin D metabolites. FACa was measured by a double radio-tracer technique and expressed as percentage of total oral dose. FACa was decreased compared with controls (34%, range: 3-46 v 65%, range: 57-73, P less than 0.01). A positive correlation (r = 0.49, P = 0.05) was found between FACa and the remaining length of small bowel (SBL). As wide variations in both SBL and duration after surgery were observed among the seventeen investigated patients, we were led to individualize less heterogeneous subgroups of patients. Better correlations were found when the patients were divided into two subgroups according to whether the time interval between the resection and the investigation was shorter (r = 0.75, n = 11, P less than 0.02) or longer (r = 0.89, n = 6, P = 0.05) than 2 years. In thirteen patients who had a SBL shorter than 100 cm, a positive correlation was observed between FACa and the time interval after surgery (months): r = 0.65, P less than 0.05. Plasma 1,25 (OH)2D was markedly reduced in the whole group (31 pmol l-1, range: 8-108) compared with controls (103 pmol-1, range: 59-134, P less than 0.01). The present study shows that in extensively small bowel resected patients, calcium absorption is reduced, the alteration being dependent both on the length of the remnant small bowel and on the time after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

What information can we gain from performing adaptive radiotherapy of head and neck cancer patients from the past 10 years?

The aim of the review was to present the current literature status about replanning regarding anatomical and dosimetric changes in the target and OARs in the head and neck region during radiotherapy, to discuss and to analyze factors influencing the decision for adaptive radiotherapy of head and neck cancer patients. Significant progress has been made in head and neck patients’ evaluation and qualification for adapted radiotherapy over the past ten years. Many factors leading to anatomical and dosimetric changes during treatment have been identified. Based on the literature, the most common factors triggering re-plan are weight loss, tumor and nodal changes, and parotid glands shrinkage. The fluctuations in dose distribution in the clinical area are significant predictive factors for patients’ quality of life and the possibility of recovery. It has been shown that re-planning influence clinical outcomes: local control, disease free survival and overall survival. Regarding literature studies, it seems that adaptive radiotherapy would be the most beneficial for tumors of immense volume or those in the nearest proximity of the OARs. All researchers agree that the timing of re-planning is a crucial challenge, and there are still no clear consensus guidelines for time or criteria of re-planning. Nowadays, thanks to significant technological progress, the decision is mostly made based on observation and supported with IGRT verification. Although further research is still needed, adaptive strategies are evolving and now became the state of the art of modern radiotherapy.     

Radiothérapie guidée par l’image dans le cancer du poumon

Image-guided radiotherapy takes place at every step of the treatment in lung cancer, from treatment planning, with fusion imaging, to daily in-room repositioning. Managing tumoral and surrounding thoracic structures motion has been allowed since the routine use of 4D computed tomography (4DCT). The integration of respiratory motion has been made with “passive” techniques based on reconstruction images from 4DCT planning, or “active” techniques adapted to the patient's breathing. Daily repositioning is based on regular images, weekly or daily, low (kV) or high (MV) energy. MRI and functional imaging also play an important part in lung cancer radiation and open the way for adaptative radiotherapy.     

Apport de la radiothérapie guidée par l’image et repositionnement du patient dans le cancer anorectal

Intensity-modulated radiation therapy is recommended in anal squamous cell carcinoma treatment and is increasingly used in rectal cancer. It adapts the dose to target volumes, with a high doses gradient. Intensity-modulated radiation therapy allows to reduce toxicity to critical normal structures and to consider dose-escalation studies or systemic treatment intensification. Image-guided radiation therapy is a warrant of quality for intensity-modulated radiation therapy, especially for successful delivery of the dose as planned. There is no recommended international or national anorectal cancer image-guided radiation therapy protocol currently available. Dose-escalation trials or expert opinions about intensity-modulated/image-guided radiation therapy good practice guidelines recommend daily volumetric imaging throughout the treatment or during the five first fractions and weekly thereafter as a minimum. Image-guided radiation therapy allows to reduce margins related to patient setup errors. Internal margin, related to the internal organ motion, needs to be adapted according to short- or long-course radiotherapy, gender, rectal location; it can be higher than current recommended planning target volume margins, particularly in the upper and anterior part of mesorectum, which has the most significant movement. Image-guided radiation therapy based on volumetric imaging allows to take target volume shrinkage into account and to develop adaptive strategies, in particular for mesorectum shrinkage during rectal cancer treatment. Lastly, the emergence of new image-guided radiation therapy technologies including MRI (which plays a major role in pelvic tumours assessment and diagnosis) opens up interesting perspectives for adaptive radiotherapy, taking into account both organs’ movements and tumour shrinkage.     

Radiothérapie guidée par l’image des cancers ORL

Intensity-modulated radiotherapy, combined with chemotherapy, is the recommended treatment of locally advanced head and neck carcinoma, as a definitive treatment or as an adjuvant treatment following surgery. This technique offers the ability to sculpt the dose closely to the tumor volume. With this close conformity, it is essential to ensure that every day during the treatment the patient position and anatomy are similar to those at the time of treatment planning. Inevitably, there will be uncertainties introduced in this process and a planning target volume margins are added around the tumour volume to compensate for these uncertainties. Various imaging technologies have been integrated with linear accelerators to deal with patient position and potentially reduce the margins. This forms the foundations of image-guided radiotherapy. In patients with head and neck carcinoma systematic and random set-up uncertainties are frequent. The 3D volumetric image guidance systems are efficient to reduce these uncertainties. After a summary about the different sources of uncertainties, this review will present successively the different techniques of image-guided radiotherapy for head and neck carcinomas, along with their advantages and limitations. Then we will focus on the methods used to reduce the set-up uncertainties and finally discuss the concept of adaptive radiotherapy and its application in clinical practice.     

Retinal arteriolar remodeling evaluated with adaptive optics camera: Relationship with blood pressure levels

AimTo research a retinal arterioles wall-to-lumen ratio or lumen diameter cut-off that would discriminate hypertensive from normal subjects using adaptive optics camera.Patients and methodsOne thousand and five hundred subjects were consecutively recruited and Adaptive Optics Camera rtx1™ (Imagine-Eyes, Orsay, France) was used to measure wall thickness, internal diameter, to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. Sitting office blood pressure was measured once, just before retinal measurements and office blood pressure was defined as systolic blood pressure > = 140 mmHg and diastolic blood pressure > = 90 mmHg. ROC curves were constructed to determine cut-off values for retinal parameters to diagnose office hypertension. In another population of 276 subjects office BP, retinal arterioles evaluation and home blood pressure monitoring were obtained. The applicability of retinal WLR or diameter cut-off values were compared in patients with controlled, masked, white-coat and sustained hypertension.ResultsIn 1500 patients, a WLR > 0.31 discriminated office hypertensive subjects with a 0.57 sensitivity and 0.71 specificity. Lumen diameter < 78.2 μm discriminated office hypertension with a 0.73 sensitivity and a 0.52 specificity. In the other 276 patients, WLR was higher in sustained hypertension vs normotensive patients (0.330 ± 0.06 vs 0.292 ± 0.05; P < 0.001) and diameter was narrower in masked hypertensive vs normotensive subjects (73.0 ± 11.2 vs 78.5 ± 11.6 μm; P < 0.005).ConclusionA WLR higher than 0.31 is in favour of office arterial hypertension; a diameter under < 78 μm may indicate a masked hypertension. Retinal arterioles analysis through adaptive optics camera may help the diagnosis of arterial hypertension, in particular in case of masked hypertension.     

Adaptative or maladaptative hypertrophy,different spatial distribution of myocardial contraction

Background: Left ventricular hypertrophy (LVH) may be an adaptative remodelling process induced by physical training, or result from pathological stimuli. We hypothesized that different LVH aetiology could lead to dissimilar spatial distribution left ventricular (LV) contraction, and compared different components of LV contraction using 2‐dimensional (2‐D) speckle tracking derived strain in subjects with adaptative hypertrophy (endurance athletes), maladaptative hypertrophy (hypertensive patients) and healthy controls. Method: We enrolled 22 patients with essential hypertension, 50 endurance athletes and 24 healthy controls. All subjects underwent traditional echocardiography and 2‐D strain evaluation of LV longitudinal, circumferential and radial function. LV basal and apical rotation and their net difference, defined as LV torsion, were evaluated. Results: LV wall thicknesses, LV mass and left atrium diameter were comparable between hypertensive group and athletes. LV longitudinal strain was reduced only in hypertensive patients (P < 0·05). LV apex circumferential strain was higher in hypertensive patients than in other groups (P < 0·001), LV basal circumferential strain, although slightly increased, did not reach significant difference. Hypertensive patients showed significantly increased rotation and torsion (P < 0·001), while no differences were observed between athletes and control. Conclusion: In patients with pathological LVH, LV longitudinal strain was reduced, while circumferential deformation and torsion were increased. No differences were observed in LV contractile function between subjects with adaptative LVH and controls. In pathological LVH, increasing torsion could be considered a compensatory mechanism to counterbalance contraction and relaxation abnormalities to maintain a normal LV output.     

Impact of positron emission tomography with computed tomography for image-guided radiotherapy

Therapeutic effectiveness in radiotherapy is partly related to correct staging of the disease and then precise therapeutic targeting. Positron emission tomography (PET) allows the stage of many cancers to be determined and therefore is essential before deciding on radiation treatment. The definition of the therapeutic target is essential to obtain correct tumour control and limit side effects. The part of adaptive radiotherapy remains to be defined, but PET by its functional nature makes it possible to define the prognosis of many cancers and to consider radiotherapy adapted to the initial response allowing an increase over the entire metabolic volume, or targeted at a subvolume at risk per dose painting, or with a decrease in the dose in case of good response at interim assessment.     

Effects of carotid baroreceptor stimulation on retinal arteriole remodeling evaluated with adaptive optics camera in resistant hypertensive patients

Background and aimBaroreceptor activation therapy (BAT) leads to a decrease in blood pressure (BP) in patients affected by resistant hypertension (RH) by reducing sympathetic outflow. This study aimed at evaluating the effects of BAT on RH patients’ retinal arteriolar microvasculature, a territory devoid of adrenergic innervation.Patients and methodsFive patients defined as affected by RH after excluding secondary causes of hypertension and based on number of antihypertensive treatments, underwent the implantation of Barostim™ neo™. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed by office and 24-hours ambulatory BP monitoring (ABPM). Adaptive Optics Camera RTX1^® (ImagineEye, Orsay, France) was used to measure wall thickness (WT), internal diameter (ID), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR). A cohort of 21 not-controlled hypertensive patients matched for age, gender and follow-up time, undergoing standard-antihypertensive therapy changes, was selected as a control group. SBP and DBP were assessed by office and home BP monitoring (HBPM). Evaluations were performed at baseline and after 6 months mean follow-up.ResultsOffice SBP decreased by 9.7 ± 12.3% and 29.7 ± 12.4% in standard-therapy and BAT group respectively, while office DBP decreased by 7.6 ± 17.4% and 14.8 ± 15.7%. Concerning ABPM/HBPM, a mean reduction of both SBP and DBP of 7.9 ± 11% was observed for the standard-therapy while a reduction of 15.8 ± 10.5% and 15.8% ± 5.3% was observed for SBP and DBP respectively in BAT group. While in the standard-therapy group a significant reduction in WLR (–5.9%) due to both ID increase (+2.3%) and WT reduction (–5.7%) was observed, without changes in WCSA (–0.3%), RH patients had a significant reduction in WCSA (–12.1%), due to a trend in both WT and ID reduction (–6.5% and –1.7% respectively), without significant changes in WLR (–2%).ConclusionWhile a reverse eutrophic remodeling was observed in patients undergoing a standard-antihypertensive treatment, hypotrophic changes were found in RH patients undergoing BAT. Despite the lack of adrenergic receptors on retinal vessels, chronic baroreflex stimulation may exert an effect on retinal microvasculature in RH patients by more systemic than local mechanisms.     

Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.