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Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions. This article deals only with indications for adults.

Includes a summary in French, Arheologia Moldovei, Vol 2-3 (1964): Arheologia Moldovei

Resume La radiotherapie abdomino-pelvienne peut induire des lesions aigues ou chroniques au sein de la paroi de l’intestin grele, denommee intestin grele radique (IGR). Le traitement de l’IGR en phase aigue est symptomatique, l’evolution etant favorable avec l’arret de l’irradiation. A l’inverse, la toxicite tardive peut survenir jusqu’a 30 ans apres l’arret de la radiotherapie, posant le probleme de son diagnostic positif. Pres d’un patient sur 5 traites par radiotherapie, va presenter des signes cliniques significatifs d’IGR, incluant un syndrome occlusif, un syndrome de malabsorption, une denutrition et/ou des complications. La prise en charge therapeutique doit etre multidisciplinaire, axee principalement sur la correction de la denutrition. Le traitement chirurgical est indique en cas de complications (i.e., abces, perforation, fistule) et/ou de resistance aux traitements medicaux ; la resection intestinale etant preferee a la simple derivation interne. Les risques majeurs en cas de resection iterative sont le syndrome de grele court et le recours a l’assistance nutritionnelle definitive.

Background: Oftentimes, obese dialysis patients develop a viable dialysis access but the access is too deep for cannulation and needs a superficialization procedure. Methods: We present our 14-patient cohort in whom we performed liposuction to superficialize viable but deep vascular accesses. Out of 14 patients, 12 had arteriovenous fistulas and 2 arteriovenous grafts. The primary end points were the ability to superficialize a completely unusable access and to remove the hemodialysis catheter (3patients), or to significantly extend the useful length of a deep access in which only a very short segment was used and to continue to use the access post-surgery without the need to place a dialysis catheter (11 patients). Results: The study goal was met in 13 out of 14 patients. In two of three patients, the catheters were removed and their access usable length was 14 and 13 cm, respectively. The accesses could be used immediately after liposuction in all patients in which this applied—11 patients. The usable access length increased from a mean of 5 to 12.7 cm. The access mean depth decreased from 10.8 mm pre-surgery to 7 mm post-surgery and 5.3 mm 4 weeks after surgery. The mean volume of fat removed was 43.8 cc. We had only one surgical complication: bleeding that was readily controlled with manual pressure. All patients were discharged to home the same day. Postoperative pain was mild. Conclusion: Liposuction is effective, safe, and seems to be the least invasive technique of superficialization.

International audience; The quality of radiation therapy has been shown to significantly influence the outcomes for head and neck squamous cell carcinoma (HNSCC) patients. The results of dosimetric studies suggest that intensity-modulated proton therapy (IMPT) could be of added value for HNSCC by being more effective than intensity-modulated (photon) radiation therapy (IMRT) for reducing side effects of radiation therapy. However, the physical properties of protons make IMPT more sensitive than photons to planning uncertainties. This could potentially have a negative effect on the quality of IMPT planning and delivery. For this review, the three French proton therapy centers collaborated to evaluate the differences between IMRT and IMPT. The review explored the effects of these uncertainties and their management for developing a robust and optimized IMPT treatment delivery plan to achieve clinical outcomes that are superior to those for IMRT. We also provide practical suggestions for the management of HNSCC carcinoma with IMPT. Because metallic dental implants can increase range uncertainties (3–10%), patient preparation for IMPT may require more systematic removal of in-field alien material than is done for IMRT. Multi-energy CT may be an alternative to calculate more accurately the dose distribution. The practical aspects that we describe are essential to guarantee optimal quality in radiation therapy in both model-based and randomized clinical trials

Funding Acknowledgements Type of funding sources: None. Introduction – Non-invasive parameters used to assess right ventricular (RV) function, i.e. tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), RV ejection fraction (RVEF), and RV free-wall longitudinal strain (RVFWLS) have shown their prognostic implications. However, since they are extremely load dependent, they do not provide an accurate representation of the RV intrinsic performance. On the other end, invasive indices of RV-arterial coupling (RVAC) derived from pressure-volume loops are not routinely performed, rising the urgency for more feasible, and reliable non-invasive estimates of RVAC. Purpose – To: i. evaluate the prognostic value of echocardiography-derived RVAC surrogates: RVEF/systolic pulmonary artery pressure (sPAP), RVFWLS/sPAP, TAPSE/sPAP, FAC/sPAP, and RV stroke volume/end-systolic volume (SV/ESV), ii. identify the cut-off values associated to all-cause mortality; and iii. compare their prognostic value with that of classical parameters of RV function. Methods – We prospectively enrolled 366 patients with various cardiac diseases, undergoing clinically-indicated comprehensive two- and three-dimensional echocardiography. Results – During a mean follow-up of 7.6 ± 1 years, 80 (21.9%) patients died. At univariable Cox regression, most of the echocardiographic parameters were related to all-cause mortality. The echocardiographic parameters with significance at univariable analysis (p Conclusion – RVAC surrogates provide incremental prognostic value compared to standard RV functional measurements. RVEF/sPAP, with a cut-off value of 1.5, was the best parameter for risk stratification, and was independently related to all-cause mortality. Abstract Figure. Prognostic value of RVAC surrogates Abstract Figure. Kaplan-Meier curves survival probability

Funding Acknowledgements Type of funding sources: None. Introduction - A by-product of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Purpose – Accordingly, we sought to: i. assess the feasibility of automated LAVmax measurement by 2DSTE; ii. compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and iii. evaluate the accuracy and reproducibility of the three echocardiography techniques. Methods – LAVmax (34­-197 mL) were prospectively obtained from 198/210 (feasibility 94%) consecutive patients with various cardiac diseases (median age 67 years, 126 men) by 2DSTE, 2DE and 3DE. Results – 2DE and 2DSTE measurements resulted in similar LAVmax values (bias = 1.5 mL, limits of agreement, LOA ± 7.5 mL), and slightly underestimated 3DE LAVmax (biases=-5 mL, LOA ± 17 mL, and -6 mL, LOA ± 16 mL, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r=.946, and r=.935, respectively; p Conclusion – Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax. Abstract Figure. Echocardiography and CMR correlations Abstract Figure. Echocardiography techniques correlations

Funding Acknowledgements Type of funding sources: None. Introduction — Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of FTR associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium (RA) and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the RV, RA and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Purpose — Accordingly, we sought to: i. study the geometry and function of the RV, RA and TA in A-FTR by two- and three-dimensional transthoracic echocardiography; and ii. compare them with those found in V-FTR. Methods — We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Results — The severity of FTR, and the degree of TA dilation were similar in A-FTR and V-FTR patients. The Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (p 2), with similar RA maximal volumes (RAVmax) between A-FTR and V-FTR (p = 0.2). Whereas, the RA minimal volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (p = 0.001). Conclusion — Despite similar degrees of FTR, RAVmax and TA size, A-FTR patients show larger RAVmin than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic and dysfunctional RV than A-FTR patients. Abstract Figure. A-FTR versus V-FTR Abstract Figure. Remodelling patterns in A-FTR and V-FTR

A thorough preoperative history is an essential component of any procedure. A good history allows the interventionalist to appropriately plan the procedure and the supplies needed, anticipate potential complications, and, ultimately, perform a successful and safe intervention.

Resume Objectifs Evaluer l’efficacite et la tolerance du rechallenge en sel de platine chez les patients presentant un carcinome epidermoide des voies aerodigestives superieures (CE VADS) recidivant apres une radiochimiotherapie a base de sels de platine. Materiel et methodes Nous avons inclus retrospectivement tout patient traite par polychimiotherapie a base de sels de platine entre 2007 et 2016 pour la prise en charge d’un CE VADS en recidive apres radiochimiotherapie a base de sels de platine (traitement exclusif ou postoperatoire). L’objectif principal etait le taux de controle de la maladie lors du rechallenge en platine. Resultats Quarante-cinq patients ont ete inclus. L’intervalle sans maladie, median apres la radiochimiotherapie, etait de 5,7 mois. Le taux de controle de la maladie lors du rechallenge platine etait de 40 %. La mediane de survie sans progression a la recidive etait 3,7 mois et la mediane de survie globale de 5,0 mois. Parmi les patients presentant une recidive dans les 6 mois suivant la radiochimiotherapie, le taux de controle de la maladie etait de 47,8 %. Un intervalle sans maladie ≥ 4,5 mois etait associe a un meilleur taux de controle de la maladie (28,5 % versus 54,8 %, p = 0,0311). Conclusion Le rechallenge en platine permet un taux interessant de controle de la maladie en situation de CE VADS recidivant apres radiochimiotherapie.

Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions. This article deals only with indications for adults.

Simple Summary The speed by which amino acids are absorbed into the blood after intake of different protein sources may affect their metabolism and utilization. A better understanding of the absorption pattern can be used to optimize the formulation of diets for pigs and to reduce the nitrogen excretion to the environment. We studied the amino acid appearance in blood of growing pigs after a meal, as influenced by protein source (wheat, soybean meal, enzyme-treated soybean meal, hydrothermally-treated rapeseed meal, casein, or hydrolyzed casein). The amino acid concentration in plasma was influenced by both time after feeding and the protein source. Overall, the highest concentrations were found at 60 min after feeding for all diets, and soybean meal had a prolonged AA absorption compared to especially casein and hydrolyzed casein. We conclude that the AA absorption profiles did not indicate clear differences among protein sources, allowing categorizing in fast and slow proteins sources, but the results show differences in the duration of AA absorption. Abstract The aim of the present study was to determine postprandial amino acid (AA) appearance in the blood of growing pigs as influenced by protein source. Seven growing pigs (average body weight 18 kg), in a 7 × 5 Youden square design, were fitted with a jugular vein catheter and fed seven diets containing wheat, soybean meal, enzyme-treated soybean meal, hydrothermally-treated rapeseed meal, casein, hydrolyzed casein, and a crystalline AA blend with the same AA profile as casein. The latter was not eaten by the pigs, therefore being excluded. Blood samples were collected at −30, 30, 60, 90, 120, 180, and 360 min after a meal and analyzed for free AA. Overall, plasma AA concentrations were highest 60 min after feeding. There were no differences in plasma AA concentration between casein and hydrolyzed casein, but soybean meal resulted in lower AA plasma concentrations compared with enzyme-treated soybean meal at 60 and 120 min after feeding. There were no differences between hydrothermally-treated rapeseed meal and soybean meal. In conclusion, the ingredients could not clearly be categorized as being slow or fast protein with regard to protein digestion and absorption of AA, but soybean meal resulted in a prolonged appearance of plasma AA compared to casein and hydrolyzed casein.

Purpose Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). Material and methods A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. Results EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. Conclusions Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Let \(\mathbb {R}\) be the set of real numbers. Throughout this book, the extended set of real numbers is \(\bar {\mathbb {R}} = \mathbb {R}\cup \{-\infty , +\infty \}\) and the extended subset of real positive numbers is \(\bar {\mathbb {R}}_+ = \mathbb {R}\cup \{+\infty \}\). An interval in \(\bar {\mathbb {R}}\) is a subset \(J\subseteq \bar {\mathbb {R}}\) with the property that, for all x, y ∈ J and for all z with \(\min \{ x, y\} < z < \max \{ x, y\}\), it follows that z ∈ J. If \(a, b\in \bar {\mathbb {R}}, a < b\), then \(]a, b[ = \{ x\in \bar {\mathbb {R}}: a < x < b\}\) is the open interval and \([a, b] = \{ x\in \bar {\mathbb {R}}: a\leq x\leq b\}\) is the closed interval of extremities a and b. Obviously \(\mathbb {R} = ]-\infty , +\infty [\) and \(\bar {\mathbb {R}} = [-\infty , +\infty ]\).

This chapter is devoted to a class of Banach spaces constructed using the notion of an integrable function—Lebesgue spaces or classical Banach spaces.

Let \( \mathbb {R}\times \mathbb {R} = \mathbb {R}^2 = \{ (x_1,x_2): x_1, x_2\in \mathbb {R}\}\) and \( \mathbb {R}\times \mathbb {R}\times \mathbb {R} = \mathbb {R}^3 = \{ (x_1,x_2,x_3): x_1, x_2,x_3\in \mathbb {R}\}\); by the usual operations of addition and multiplication with real scalars (operations defined on the coordinates), these sets are organized like real vector spaces.

Abdominal pelvic radiation therapy can induce acute or chronic lesions in the small bowel wall, called radiation enteritis. Treatment of acute radiation enteritis is essentially symptomatic; symptoms regress when radiation is discontinued. Conversely, late toxicity can occur up to 30 years after discontinuation of radiation therapy, posing diagnostic problems. Approximately one out of five patients treated by radiation therapy will present clinical signs of radiation enteritis, including obstruction, malabsorption, malnutrition and/or other complications. Management should be multidisciplinary, centered mainly on correction of malnutrition. Surgery is indicated in case of complications (i.e., abscess, perforation, fistula) and/or resistance to medical treatment; intestinal resection should be preferred over internal bypass. The main risk in case of iterative resections is the short bowel syndrome and the need for definitive nutritional assistance.

Objectives: In this Covid-19 pandemic, onco-hematological patients are at higher risk of severe infection because of both their immunosuppressive state caused by malignancy and treatments and their recurrent hospital accesses At our cancer centre (IRST), following national authorities and scientific societies recommendations, we set up a model for reduction of risk of Covid-19 positive accesses through sequential actions on patients, caregivers and workers In this work we give an estimate of reduction of risk of Covid-19 positive accesses Methods: Covid-19 positive accesses baseline Absolute Risk (AR, ratio between the number of infected subjects accesses and the total number of accesses) for patients, caregivers and workers was estimated in the period from March, 11 to March, 31 Five risk reduction actions were implemented: (1) all procedures judged as deferrable by physicians have been postponed, (2) by-phone triage and (3) on-site triage have been activated to avoid accesses of suspected cases patients and caregivers For workers (4) special leaves and (5) smartwork were encouraged For each of these actions we estimated Absolute Risk Reduction (ARR) and Relative Risk Reduction (RRR) Results: In the analysis period we estimated 50 Covid-19 positive accesses: 14 for patients, 7 for caregivers, 29 for workers (AR 0 129%, 0 087%, 0 316% respectively) We measured 9 avoided accesses for patients (ARR: 0 084%, RRR: 65 4%), 5 for caregivers (ARR: 0 061%, RRR: 69 5%), 17 for workers (ARR: 0 184, RRR: 58 0%);for a total of 31 accesses potentially avoided thanks to the 5 actions Conclusions: During the pandemic IRST never stopped providing care to the patients, the implemented actions allowed a risk reduction that can be an example of how to face this pandemia maintaining both continuity of care and safety for patients and staff in a context of frailty such as a cancer centre

Resume Objectif Evaluer en pratique quotidienne la faisabilite de la radiochimiotherapie postoperatoire chez les patients traites pour un carcinome epidermoide des voies aerodigestives superieures (CEVADS) a haut risque de recidive. Methode Etude retrospective monocentrique. Tout patient traite par radiochimiotherapie postoperatoire a base de cisplatine pour un CEVADS a haut risque etait eligible. L’objectif principal etait d’evaluer le taux de realisation complete de la radiochimiotherapie postoperatoire et l’impact de divers facteurs cliniques. Les objectifs secondaires etaient de preciser l’impact de la realisation complete du traitement sur la survie et les toxicites aigues et tardives. Resultats Cent six patients ont ete inclus. Parmi les patients, 24,5 % avaient une comorbidite severe. La radiochimiotherapie etait realisee en integralite chez 61 patients (57,5 %). La radiotherapie etait suspendue pendant plus de 3 jours chez 16 patients (15,1 %). La troisieme cure de cisplatine concomitante ne pouvait etre realisee chez 34 patients (32,1 %). La diminution du debit de filtration glomerulaire pre-therapeutique (p = 0,003) etait significativement associee a un risque d’interruption de traitement tandis que des resultats suggestifs concernant ce risque d’interruption en cas d’amaigrissement > 5 % en cours de traitement (p = 0,026). La realisation complete de la radiochimiotherapie n’etait pas associee a une difference significative en termes de survie globale (p = 0,441) et de survie sans progression (p = 0,81). Une insuffisance renale sequellaire a ete retrouvee chez 14,9 % des patients. Dix cas (9,4 %) d’osteoradionecrose ont ete rapportes. Conclusion Le taux de realisation complete de la radiochimiotherapie postoperatoire etait comparable a celui des essais cliniques malgre les comorbidites frequentes et l’etat nutritionnel precaire. Un support nutritionnel precoce reste un point cle afin de permettre la realisation du traitement dans des conditions optimales.

Background In the past few years more than 30,000 asylum seekers arrived in Emilia-Romagna region. Guidelines were developed to screen the newly arrived, mainly focused on communicable diseases (CDs). However, asylum seekers who are out of the institutional reception system do not have access to such screenings. In order to assess the implementation and reach of these guidelines with respect to the target population, in 2019 a mixed-method survey was carried out. Methods A questionnaire with 35 closed and 11 open questions, based on a synthesis of the regional and national guidelines, was carried out with referents of the regional clinics that provide healthcare to asylum seekers. The collected questionnaires were processed through descriptive statistical analysis for the closed questions and text analysis for the open questions. Results Questionnaires were collected from 14 clinics. All clinics provide first visit and screening for CDs upon arrival, following the regional guidelines. However, enrolment in the national healthcare system was found to be delayed for periods of up to 6 months, resulting in discontinuity of care. Administrative and cultural barriers in accessing health and social services were repeatedly reported, the latter often linked to lack of cultural mediation services. Financial barriers were also reported, particularly with respect to dental care and pharmaceuticals. Results also show that asylum seekers within the institutional reception system can more easily overcome the reported barriers compared to those out of the system. Such inequality in accessing healthcare is reported also for the TB screening process. Conclusions Even if access to healthcare for asylum seekers is regulated by norms and guidelines, barriers are consistently reported. Moreover, asylum seekers within or outside the reception system face different barriers in accessing healthcare services. Such local evidence can be very relevant to inform actions that improve health equity. Key messages Even if access to healthcare for asylum seekers is regulated by law, barriers are consistently reported and impact disproportionately on those who are out of the institutional reception system. A mixed-method approach that generates local evidence on the barriers that asylum seekers face in accessing healthcare and on their causes is key to inform actions that improve health equity.

Background In Italy, recent changes in migration flows posed complex public health challenges. The Emilia-Romagna region (ERR) was one of the first regions to adopt specific policies addressing the health of newly arrived asylum seekers. In our study, we analysed the regional health system response comparing it to the regional and national guidelines, in order to assess its strengths and its critical areas. Methods In 2019, we conducted a survey among the referents of the regional clinics that provide healthcare to asylum seekers, in order to learn about local policies, challenges and best practices. A questionnaire with 35 closed and 11 open questions was administered and analysed through descriptive statistical analysis and text analysis. Results Regional policies showed good responsiveness and Local Health Authorities (LHAs) adhered to the guidelines. A special permit was introduced to grant asylum seekers access to healthcare, which also allowed integration of health data into the regional health information system. However, data integration was done in only 2 clinics out of 14. Instances of discretion in issuing the special permit were reported, due to ambiguity in the rules and inadequate training of office workers. Policies and LHAs protocols focused greatly on the arrival phase and on Communicable Diseases (CDs) surveillance. Other areas - such as protection of vulnerable groups, health promotion, NCDs - were prioritized in the national guidelines, but unevenly considered throughout the region, also due to lack of resources. Some clinics responded autonomously to these gaps with local resources. Conclusions The ERR health response to the influx of asylum seekers was rapid but incomplete. Interventions focused more on CDs surveillance than on responding to asylum seekers' health needs in terms of quality, access and equity. Areas to be strengthened include protection of vulnerable groups, health promotion and NCDs, together with coordination and long-term planning. Key messages The Emilia-Romagna region health response to the influx of asylum seekers reflects an emergency approach focused on communicable diseases, while NCDs and health promotion are relatively neglected. The health system in Emilia-Romagna needs to be strengthened in its capacity to respond to asylum seekers’ health needs. Health policies and practices should be planned to ensure equity and quality.

Minimal invasive surgery and reconstructive surgery tend to become the standard in France in the management of head and neck tumors. The use of endoscopic approaches (through endoscopic endonasal/transoral approaches±robot-assisted) instead of open surgery and the use of reconstructive surgery using autologous (flaps) or heterologous materials aim to reduce surgical morbidity by making-up for the loss of substance to restore the function. The impact of these substantial changes in surgical techniques has not been assessed with respect to postoperative radiotherapy practice. Endoscopic endonasal approaches result, however, in piecemeal resection, which, along the analysis of resection margins (a key prognostic factor), make the interpretation of the quality of resection more complex for radiation oncologists. The definition of tumour sub-volumes to be irradiated and doses to these sub-volumes then requires accurate histosurgical mapping and close multidisciplinary consultation between surgeons, pathologists, radiologists and radiation oncologists. Similarly, the increasing use of various types of flaps (of soft tissue or bone flaps), adapted to the patient and tumor anatomy, is associated with substantial modifications to the operating bed. The delineation of tumour volumes in postoperative radiotherapy is made more complex. Tremendous multidisciplinary efforts should now be initiated to fully take advantage of surgical advances and to further optimize the therapeutic index by making radiotherapy also less toxic, i.e. "mini-morbid".

Objective To assess the feasibility in routine practice of postoperative chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. Method A single-center retrospective study recruited all patients receiving postoperative cisplatin chemoradiotherapy for HNSCC at high risk of recurrence. The main endpoints were the rate of complete postoperative chemoradiotherapy and the impact of various clinical factors. Secondary endpoints comprised the impact of completion of therapy on survival and on acute and late toxicity. Results One hundred and six patients were included. 24.5% showed severe comorbidity. Chemoradiotherapy was complete in 61 patients (57.5%). Radiation therapy was interrupted for > 3 days in 16 patients (15.1%). The 3rd concomitant cisplatin course could not be implemented in 34 patients (32.1%). Low pre-treatment glomerular filtration rate was significantly associated (p = 0.003) with treatment interruption; > 5% weight-loss during treatment showed suggestive association (p = 0.026). Completion of treatment was not associated with any significant difference in overall survival (p = 0.441) or progression-free survival (p = 0.81). 14.9% of patients showed post-treatment kidney failure; there were 10 cases of osteoradionecrosis (9.4%). Conclusion The rate of complete postoperative chemoradiotherapy was comparable to that reported in clinical trials, despite frequent comorbidity and poor nutritional status. Early nutritional support is a key factor for treatment under optimal conditions.

Median survival for recurrent/metastatic head and neck squamous cell cancer (HNSCC) patients is about 10 months after first-line best systemic treatment. We aimed to assess current approaches of oligometastatic HNSCC patients by the analysis of current concept and published data (1995–2017) in this population. Five-year survival rates are over 20% in selected patients who undergo metastasis-directed therapy by either surgery or stereotactic irradiation. Human papillomavirus(+) HNSCC patients have more disseminated metastases but respond more favorably and also benefit from ablative treatments. Treatments of oligometastases are expanding rapidly. Unmet needs include revised imaging follow-up strategies to detect metastases earlier, identification of predictive noninvasive biomarkers for treatment guidance, assessment and corrections of biases in current studies and randomized clinical trials.

Background and objectives: We evaluated the location and structure of the fibrous sheath formed after the placement of tunneled, cuffed hemodialysis catheters in large animals, 70 kg pigs. We focused on describing the location of the fibrous sheath in relation to the catheter. Its location explains the fibrous sheath’s ability to cause catheter dysfunction by covering the catheter exit ports located at the catheter’s tip. Design: We used three animals. Each animal had a tunneled, cuffed, 15-French diameter hemodialysis catheter placed in the external jugular vein, with the tip at the junction of the superior vena cava and the right atrium. Two animals were sacrificed at 5 weeks and one animal at 17 weeks after catheter placement. The catheter and surrounding tissues were removed in one block. The fibrous sheath was dissected and longitudinally cut along the catheter to evaluate its extension in relation to the catheter. Relevant portions of the fibrous sheath were sent for pathology examination. Results: The fibrous sheath covered the catheter in its entire length and circumference. It started at the entry site and continued without any interruption along the entire length of the catheter, including the tip. Its average thickness is 1 mm and has an inner cellular/inflammatory layer comprising lymphocytes, plasma cells, neutrophils, macrophages, multinucleated giant cells, and spindled cells and an outer layer comprising a mixture of collagen and fibroblasts. Conclusion: Our model showed that the fibrous sheath forms around all catheters and covers them in their entire length and circumference without any gaps.

Before the introduction of intensity-modulated radiation therapy (IMRT), few teams used to implant a pelvic tissue expander to keep the bowel away from the radiation field, so as to reduce the risk of acute and late enteritis. However, this unexpected surgery could impact patient’s overall treatment and may be no more necessary in the era of modern radiotherapy. This is a retrospective cross-sectional study including 13 patients who underwent tissue expander implantation before radiotherapy or chemoradiotherapy for rectal or anal carcinoma between November 2008 and March 2019. First, we aim to show that IMRT could sometimes be insufficient to respect dosimetric constraints, and then we aim to report the impact of tissue expander implantation on the global strategy of care of patients with anal and rectal cancers. Seventy-seven percent of the included patients were treated for anal neoplasms, while the remaining 23% had locally advanced rectal cancer. The median follow-up since implantation of the expander was 51 months [3.7–115]. Three patients recurred. One patient developed grade III toxicity related to the implantation of a tissue expander. The delay between diagnosis and the start of irradiation was significantly prolonged (median of 3 months), requiring unusual induction chemotherapy. Implantation of tissue expander prior to chemoradiotherapy should be considered, even in the era of IMRT, when irradiated peritoneal cavity volume (V15Gy–V45Gy) far exceeds usual dose constraints. However, it impacts the global strategy of care by delaying the start of irradiation, by introducing induction chemotherapy, and rarely by causing post-operative complications.

Objective To evaluate platinum rechallenge efficacy and tolerance in patients presenting recurrent head and neck squamous cell carcinoma (HNSCC) after platinum-based chemoradiation. Materials and methods We retrospectively included all patients treated from 2007 to 2016 by platinum-based polychemotherapy for recurrence of HNSCC previously treated by primary or postsurgical platinum-based chemoradiation. The primary end-point was disease control rate (DCR) on platinum rechallenge. Results Forty-five patients were included. Median disease-free interval (DFI) after chemoradiation was 5.7 months. DCR on platinum rechallenge was 40%. Progression-free survival at recurrence was 3.7 months and overall survival 5.0 months. DCR in patients with recurrence within 6 months of chemoradiotherapy was 47.8%. DFI > 4.5 months was associated with better DCR: 28.5% versus 54.8%; P = 0.0311. Conclusion Platinum rechallenge provided good DCR in recurrent HNSCC after chemoradiation.

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

e15501 Background: Concomitant radiochemotherapy is the standard treatment of locally advanced epidermoid anal canal carcinoma (EACC) but conventional radiotherapy (RT) frequently induces significant non-hematological toxicities, resulting in long treatment breaks. Given the numerous anatomic pelvic structures, EACC has become of interest for Intensity-Modulated Radiation Therapy (IMRT) despite the induced cutaneous toxicities responsible for RT breaks. Given the deleterious effect of treatment duration on local control and survival in other epidermoid cancers, continuous IMRT is challenging to control EACC. Several SIB-IMRT schedules provided similar results with moderate doses and schedules delivering higher doses with short breaks. Yet, standard SIB-IMRT schedule in EACC still not exists. We propose to concomitantly assess the safety and efficacy of continuous SIB-IMRT without planned breaks and concurrent chemotherapy (CT) to improve the treatment of locally advanced EACC by reducing the proportion of patients (pts) requiring RT breaks for toxicities. Methods: The CANAL-IMRT-01 phase 2 trial (NCT02701088) targets pts with histologically proven EACC candidate for concomitant RT of pelvic and inguinal nodes plus CT. Applying a two-step Bryant & Day design, the main criterion is based on both efficacy and safety. Efficacy is defined as the proportion of pts alive with no local disease progression 3 months after the end of IMRT; safety is defined as the proportion of pts with no RT breaks required by grade ≥3 toxicities. Assuming the unacceptable and acceptable proportions of pts without toxicity requiring IMRT break are 60 and 80% respectively, the unacceptable and acceptable 3-month-progression-free-survival are 80 and 90%, 14 assessable pts at first step and 46 in the second are required (alpha risk 5%, 90% power). To anticipate a 10% drop out rate, 16 pts were needed in first step, with ≥11 objective local responses and ≤6 toxicity-induced IMRT breaks to pursue. Treatment consists in 50 days of concomitant CT (2 cycles of 5FU and Mitomycin-C) and SIB-IMRT delivered by helical tomotherapy: 61.2Gy/1.7Gy to the primary tumor, 57.6Gy/1.6Gy to involved nodes, and 54/1.5Gy to elective pelvic lymph nodes. Results: From December 2015 to June 2017, 16 pts were enrolled: 11 female (73%), median age 62 [55-66]. 15 pts were assessable for efficacy and safety. All 15 pts had a 3-month locoregional response (12 complete responses, 3 partial responses). SIB-IMRT breaks were required by toxicities for 4 out of 15 pts: G1 radiodermitis, G2 inguinal and epithelitis, G1 fever, G3 anorexia and vertigo. Conclusions: The planned interim analysis of continuous SIB-IMRT plus CT allowed pursuing this phase 2 trial to assess the relevance of such schedule for locally advanced ASCC. Enrolment is still ongoing. Clinical trial information: NCT02701088.

We prove that the Dudley metric is complete on the space of Young measures and then we study the uniform continuity of functional \(u\mapsto \int _{\Omega }f(t,u(t)) dt\) on subsets of \({\mathcal {L}}^{1}(\Omega , \mathbb R^{s})\). The results are applied on Sobolev space \({\mathcal {W}}^{1,1}(\Omega , \mathbb R^{m})\hookrightarrow {\mathcal {L}}^{1}(\Omega , \mathbb R^{m+m\times d})\) .

Resume La radiotherapie conformationnelle avec modulation d’intensite est la technique recommandee pour le traitement des cancers des voies aerodigestives superieures. La protontherapie permettrait de diminuer le volume de tissu normal irradie et ainsi de reduire le risque de dysphagie et de dysgueusie. Une recherche bibliographique exhaustive a ete realisee a l’aide du moteur de recherche PubMed en se focalisant sur les articles traitant des difficultes physiques de la protontherapie pour les cancers des voies aerodigestives superieures. Le controle des incertitudes liees a la penombre distale est important en ORL, notamment en presence de materiel implante ayant une composition stœchiometrique incertaine (tels que les implants dentaires metalliques) et en presence de milieux heterogenes (succession de tissu et d’air dans les cavites sinusiennes). La mise en etat buccodentaire est donc particuliere en protontherapie. Certaines incertitudes peuvent etre minimisees au moment de la planification du traitement (optimisation robuste pour les variations inter et intra fractions de la composition du milieu et pour la calibration entre unites de Hounsfield et pouvoir d’arret des protons). En revanche, comme en RCMI, les variations morphologiques du patient necessitent, une adaptation du plan de traitement sur un nouveau scanographe. Les etudes dosimetriques et les quelques etudes cliniques comparant photon- et protontherapie ont bien montre l’interet des protons dans cette localisation. La protontherapie dans les cancers des voies aerodigestives superieures est donc prometteuse mais necessite la mise au point de procedures permettant un controle robuste des incertitudes, pour rendre le traitement optimal et utilisable en pratique clinique.

International audience; Introduction Le carcinome adénoïde kystique est une tumeur rare de la sphère ORL pour laquelle peut se poser la question d’un traitement systémique. L’objectif de cette revue est de faire l’état des lieux des traitements systémiques (chimiothérapies, thérapies ciblées, immunothérapies) au stade de rechute locale ou métastatique. Méthodes Les articles traitant des thérapies systémiques de la sphère ORL de l’adulte, en situation métastatique ou localement avancée, comprenant au moins 10 patients ont été inclus. Résultats Quarante articles ont été sélectionnés dans cette revue. Le taux de réponse objective sous chimiothérapie était en moyenne < 10 % (0–70 %), avec des réponses objectives en monothérapie sous cisplatine, mitoxantrone, vinorelbine et éribuline, et en bithérapie par cisplatine-vinorelbine. Les inhibiteurs de l’EGFR ont permis d’obtenir 40 % de réponse objective en association avec de la chimiothérapie. Les inhibiteurs du VEGF et de l’histone désacétylase ont permis une stabilisation de la maladie prolongée chez des patients en progression, avec 10 % de réponses objectives. Les inhibiteurs de c-KIT en monothérapie ont permis d’obtenir < 5 % de réponse objective. Les inhibiteurs directs de la voie PI3 K/AKT/mTOR ont pour l’instant obtenu 0 % de réponse objective. Discussion Les meilleurs taux de réponse objective ont été obtenus avec la bithérapie à base de cisplatine-vinorelbine. De nombreuses anomalies moléculaires ont été identifiées. Les anti-EGFR, anti-VEGF et HDAC permettent des stabilisations prolongées. La présentation des dossiers en réunion de concertation pluridisciplinaire (RCP) de recours, telle que le Réseau d’expertise français des cancers ORL rares (REFCOR) et les RCP moléculaires, devrait être proposée, permettant notamment de diriger les patients vers des essais thérapeutiques.

To evaluate the frequency of use, modalities and potential interest of locoregional irradiation (LRT) in patients with upfront metastatic head and neck squamous cell carcinoma (HNSCC).Retrospective multicentric study. Were included all patients presenting an upfront metastatic HNSCC treated by platin-5FU- cetuximab based regimen, from 2008 to 2016. Patients with past history of cervical irradiation or HNSCC within the 5 years before metastasis diagnosis were excluded.65 patients were included. 25 patients (38%) presented a response or stable disease with chemotherapy. Forty-one patients (63%) underwent a locoregional irradiation: 5 patients before chemotherapy (upfront RT), 13 patients with stable disease or response after chemotherapy (consolidation RT), and 23 patients with progressive disease. Median overall survival (OS) was 11.6 months, median progression free survival was 7.9 months. OS was significantly improved for patients who underwent LRT (median OS 16.1 vs 7.5 months, p 0.01). Among patients who received LRT, OS trended to be better if LRT was performed as consolidation RT compared to upfront RT (median OS of 22.1 vs 15.5 months, p = 0.11). Among patients with stable disease or response after chemotherapy, there was a non-significant better OS for the 13 patients treated by LRT (median OS 22.1 vs 11.8 months, p = 0.21)). Radical dose was not associated with better locoregional control compared to palliative dose (p = 0.37).LRT is frequently performed during management of upfront metastatic HNSCC and associated with better OS. Non-progressive disease after firs-line chemotherapy seems a good way to select patients who would benefit from radical LRT.

Systemic capillary leak syndrome (SCLS) is a disorder characterized by increased vascular permeability with intermittent acute episodes of profound capillary leak that may result in hypotension or shock. A rarely described chronic form of SCLS (cSCLS) presents as refractory edema, with pleural and/or pericardial effusions and hypoalbuminemia. These entities are differentiated by massive and periodic episodes of capillary leak, which can result in shock in SCLS, and chronic refractory edema in cSCLS. The etiologies of these disorders are poorly understood, but both acute and chronic forms often present with an associated monoclonal gammopathy. Flares of the SCLS have been reduced by treatment with intravenous immune globulin (IVIG). Only six cases of cSCLS have been reported, and previous treatments have included steroids, terbutaline, and theophylline. Based upon the reported responses of SCLS to IVIG, we present the case of a 54-year-old man with cSCLS where ongoing treatment with IVIG resulted in a marked and sustained improvement in the signs and symptoms of the capillary leak syndrome. .

Central venous catheters remain a vital option for access for patients receiving maintenance hemodialysis. There are many important and evolving clinical and regulatory considerations for all stakeholders for these devices. Innovation and transparent and comprehensive regulatory review of these devices is essential to stimulate innovation to help promote better outcomes for patients receiving maintenance hemodialysis. A workgroup that included representatives from academia, industry, and the US Food and Drug Administration was convened to identify the major design considerations and clinical and regulatory challenges of central venous catheters for hemodialysis. Our intent is to foster improved understanding of these devices and provide the foundation for strategies to foster innovation of these devices.

Background: Currently, there is insufficient knowledge about the surgical anatomy and surgical techniques in large animals that can be used to test medical devices designed for human use. We encountered this problem in our study requiring the placement of jugular vein, tunneled, cuffed hemodialysis catheter in 70 kg pigs. Despite the operator’s extensive expertise in placing tunneled hemodialysis catheters in humans, the important differences in anatomy made the procedure and choosing the appropriate catheter length challenging. Methods: The following article describes the anatomy and our technique for the placement of tunneled hemodialysis catheter in the pig model. Results: We consider our surgical technique to be sound because in all animals the catheters were placed in the desired location, the procedures were well tolerated by the animals, and there were no immediate or late complications. Conclusion: We present our experience to help other researchers who might encounter the same problem.