[Adverse events in biologics for severe asthma]. / Effets indésirables des biothérapies de l'asthme sévère.

INTRODUCTION: Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the development of biomedicines, of which there are currently five available in France, with a safety profile that appears favorable but remains uncertain due to a lack of real-life experience with these new molecules. STATE OF KNOWLEDGE: Although relatively benign, the adverse effects of biologics are diverse. Headache, joint pain, skin reactions at the injection site, fever and asthenia are commonly observed during the different treatments. Ophthalmological complications seem restricted to dupilumab, with numerous cases of keratitis and conjunctivitis in patients with atopic dermatitis. Several respiratory complications have also been observed, essentially consisting in pharyngitis and other upper respiratory infections. Hypereosinophilia may occur, mainly with dupilumab, requiring investigation of systemic repercussions or vasculitis. Allergic reactions are uncommon but require careful monitoring during initial injections. CONCLUSION: Biologics for severe asthma are recent drugs with a favorable safety profile, but with little real-life experience, justifying increased vigilance by prescribing physicians.

[Correlation between Objective structured clinical examinations (OSCE) and knowledge examination scores and analysis of factors associated with better OSCE success in fourth and fifth year medicine students at Dijon university hospital]. / Corrélation entre les notes obtenues aux ECOS et aux épreuves de connaissances et analyse des facteurs associés à une meilleure réussite aux ECOS chez les étudiants de DFASM1 et 2 au CHU de Dijon.

RATIONALE: Objective structured clinical examinations (OSCEs) were introduced to evaluate students not only on their knowledge, but also on their clinical skills and attitudes. The objectives were to study the correlation between OSCE scores and scores obtained to traditional knowledge examinations and to analyse factors associated with better OSCE performance in DFASM1 and 2 students at Dijon university hospital. METHODS: This was a prospective observational study conducted among all fourth and fifth year medical students in Dijon. The scores on the OSCE elective tests (2022) and the average score on the knowledge tests (2021-2022) were collected and their correlation measured. A questionnaire asked students about their demographic characteristics, their investment in formative and practicum OSCEs, their level of empathy (Jefferson questionnaire) and their personality traits (NEO-Pi-R). RESULTS: Of 549 students, 513 completed all tests. Scores on OSCE and faculty knowledge tests were correlated (r=0.39, P<0.001). Of these, 111 (20%) students responded to the questionnaire, and 97 were analized. We did not observe any significant difference between students who performed better on OSCEs than on knowledge tests and those who did not, regarding their age, their investment in formative tests, their personality traits or their level of empathy. CONCLUSION: Our results underline the need to optimize the evaluation of empathy and clinical skills in OSCE tests, using new tools, in order to better discriminate between students on these skills.

[Sclerosing pneumocytoma: A rare and benign tumor]. / Le pneumocytome sclérosant : une tumeur rare et apparemment bénigne.

INTRODUCTION: Sclerosing pneumocytoma is a benign and rare lung tumor affecting epithelial cells. In most cases, patients are asymptomatic and the diagnosis is made on an X ray or a CT scan performed for other enquiry. Sex ratio favors women. Epidemiological studies report that middle-aged Asian women are more frequently affected. Radiological investigations find a solitary nodule or a mass with peripheric localization. When performed, histological analysis shows a tumor composed of at least two of the four following architectures: papillary, sclerosing, hemangiomatous and solid, with two types of cells that can be round or cubic cells. CASES REPORT: We report two cases of multiple sclerosing pneumocytoma in two caucasien men. The first patient was asymptomatic, the second complain from moderate dyspnea. A wedge resection was performed in both, allowing diagnosis. Anatomopathology revealed respectively a predominant sclerosing and solid architecture and a sclerosing and papillary architecture. There was no progression of the other concomitant nodules after three years follow-up. CONCLUSION: Pneumocytoma is a benign, slow-growing tumor with good prognosis.

Bilateral vocal cord paralysis after endoscopic placement of fully covered self-expandable metal stent for palliative treatment of malignant proximal esophageal obstruction: two case reports.

BACKGROUND: Oesophageal stents have several well-known respiratory complications, including aspiration pneumonia, fistula and airway compression. However, bilateral vocal cord paralysis has rarely been described. METHODS: We describe two patients who presented with refractory dysphagia due to malignant proximal oesophageal strictures. Both received palliative treatment consisting of fully covered self-expandable metal stents that were placed across the strictures. RESULTS: Both patients developed inspiratory stridor and acute hypoxemic respiratory failure shortly after the stent was placed. Flexible bronchoscopy revealed vocal cord paralysis in paramedian position, potentially due to extrinsic compression of the posterior branch of the recurrent laryngeal nerve following the progressive opening of the esophageal prosthesis. One patient recovered after the stent was removed. CONCLUSIONS: Bilateral vocal cord paralysis is a rare but potentially fatal complication of proximal esophagus stenting.

Case series on multiple prostate re-irradiation for locally recurrent prostate cancer: something ventured, something gained.

The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.

Radiotherapy in the management of gist: state of the art and new potential scenarios.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The main treatment for localized gastrointestinal stromal tumors is surgical resection. Unresectable or advanced GIST are poorly responsive to conventional cytotoxic chemotherapy but the introduction of tyrosine kinase inhibitors (TKIs) marked a revolutionary step in the treatment of these patients, radically improving prognosis and clinical benefit. Historically GIST has been considered radiation-resistant, and the role of radiotherapy in the management of patients with GIST is currently restricted to symptomatic palliation in current treatment guidelines. CASE PRESENTATION: Here we report two patients affected by metastatic GIST, treated with radiotherapy and radiosurgery in combination with TKIs, achieving an unexpected objective response in the first case and a significant clinical benefit associated with a local tumor control of several months in the second case. CONCLUSIONS: These and other successful experiences that are progressively accumulating, open up new scenarios of use of radiation therapy in various settings of treatment. GIST is not universally radioresistant and radiotherapy, especially if combined with molecularly targeted therapy, can improve the outcomes for patients diagnosed with GIST.

Kink energy and kink dipole moments on vicinal Au(001) in halide electrolytes.

Using electrochemical scanning tunnelling microscopy, we measured the potential-dependent kink energy and the corresponding dipole moments of kinks at step edges on vicinal Au(001) surfaces in chloride and bromide containing electrolytes. Combining the results of the potential dependence of the kink energy with impedance spectroscopy data for the surface charge, we can directly deduce the dipole moment of kinks at the Au steps with co-adsorbed Cl(-) and Br(-), respectively. We find µ(Cl) = (6.0 ± 0.7) × 10(-3) eÅ and µ(Br) = (10.1 ± 0.6) × 10(-3) eÅ.

CyberKnife robotic image-guided stereotactic radiotherapy for oligometastic cancer : A prospective evaluation of 95 patients/118 lesions.

PURPOSE: To evaluate the outcome of robotic CyberKnife (Accuray Inc. Sunnyvale, USA)-based stereotactic radiotherapy (CBK-SRT) for oligometastic cancer patients. PATIENTS AND METHODS: Between May 2007 and December 2009, 95 patients with a total of 118 lesions underwent CBK-SRT (median dose 24 Gy in 3 fractions). INCLUSION CRITERIA: adult patients with limited volume cancer; suitability for SRT but not for other local therapies. Primary diagnoses included breast, lung, head and neck, gastrointestinal and other malignancies. Prostate cancer patients were excluded. Concomitant systemic therapy was given in 40 % of cases and median follow-up was 12 months. Toxicity and tumor response were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Scale and Response Evaluation Criteria in Solid Tumors RECIST. RESULTS: Toxicity was rare and observed mainly in patients with comorbidities or uncontrolled cancer. Out of 87 evaluable lesions, complete radiological response, partial response, stabilization and progressive disease were observed in 15 (17 %), 25 (29 %), 34 (39 %) and 13 (15 %) lesions, respectively. Upon restricting the analysis to lesions treated with CBK-SRT alone (no concomitant therapy), response- and local control (LC) rates remained similar. Actuarial 3-year in-field progression-free survival- (i.e. LC), progression-free survival- (PFS) and overall-survival (OS) rates were 67.6, 18.4, and 31.2 %, respectively. LC was reduced in cases of early recurrence. OS- and cause-specific survival (CSS) rates were significantly lower in patients treated for visceral lesions. Failures were predominantly out-field. CONCLUSION: CBK-SRT is a feasible therapeutic approach for oligometastastic cancer patients that provides long-term in-field tumor control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.

Feasibility of the sentinel node biopsy in anal cancer.

AIM: Anal cancer is a rare neoplasm. According to a European Organization for Research and Treatment of Cancer multivariate analysis, synchronous inguinal lymph node metastasis occurs in 10-25% of patients and constitutes an independent prognostic factor for local failure and overall mortality. METHODS: Inguinal lymph node status was assessed using the sentinel node technique in 35 patients with anal cancer. RESULTS: Histology revealed 23 squamous carcinomas, 10 basaloid carcinomas, 1 squamous carcinoma with basaloid areas and 1 spinocellular epithelioma associated with areas of Bowen's disease. Disease stage was T1 in 5 patients, T2 in 18, T3 in 11 and T4 in 1 patient. Lympho-scintigraphy using a GE Millennium gamma camera was performed after peritumoral injection of 37 MBq of 99mTc colloid. Surgical sentinel node biopsy with a portable Scintiprobe MR 100 (Politech, Carsoli, Italy) had a detection rate of 97.1%. Inguinal metastases were detected in 7 (20%) patients, in 2 of which metastasis was bilateral. CONCLUSIONS: Given the correlation between prognosis and node involvement, sentinel node biopsy can be considered a simple method for adequate pretreatment staging of anal carcinoma. Use of the technique could avert the need for prophylactic inguinal radiotherapy in N0-N1 patients, thus reducing the morbidity associated with inguinal radiotherapy. Consistent follow-up is required to evaluate long-term results:

[The technique of sentinel lymph nodes in patients with anus neoplasm]. / La tecnica del linfonodo sentinella nei pazienti affetti da neoplasia dell'ano.

Anal cancer is a rare neoplasm, representing 1-2% of all large bowel cancers. Surgical excision by abdominoperineal resection has been the standard treatment. In the 1920s and 1930s inguinal node dissection was included in the surgical management of these patients. In the 1950s it was evident that the morbidity associated with lymphnode dissection was much greater than any survival benefit and this procedure was abandoned. Since 1974 "multimodality treatment" with a combination of radiation and chemotherapy has become the standard treatment. Synchronous inguinal lymph node metastases occur in 10-25% of patients and metachronous metastases have been reported in 5-25% of cases. Inguinal lymph node metastases are an independent prognostic factor for local failure and overall mortality by a multivariate analysis of EORTC. In order to assess inguinal lymph node status we applied the sentinel node technique to patients affected by anal cancer. Fifteen patients were studied with a lymphoscintigraphy after peritumoral injection of 37 MBq of Tc-99m colloid. A surgical biopsy of sentinel node was performed in all patients with a detection rate of 100%. Inguinal metastases occurred in 4 patients (26.6%), and in 2 cases metastases were located bilaterally. Twelve patients (80%) were treated in local anesthesia and they were dismissed the same day of surgical procedure. No major complication occurred. Considering the strong correlation between prognosis and node involvement, we consider this technique an important and simple method for evaluating the lymph node status and for an adequate pre-treatment staging of anal carcinoma. fundamental in the choice of radiation plane. In particular inguinal radiotherapy could be reserved for N1 patients only. avoiding the morbidity related to this procedure in N0 patients. Further studies are required to confirm these results and a consistent follow-up will be necessary to evaluate long-term results particularly in those patients (N0) who have not been treated with prophylactic inguinal radiotherapy.

Treatment of malignant neoplasms of the parotid gland.

In this study we evaluated the effects of surgical and radiotherapy treatment on local control in 126 patients with malignant tumors of the parotid gland. The most frequently observed malignant tumors were high-grade tumors (68%). Surgical treatment was performed in 81 patients (83.5%). Total conservative parotidectomy was the most frequent procedure (74%), and radiotherapy was performed in 81 patients (83.5%). The global survival rate was approximately 54% at 5 years, whereas disease-free survival was 47% at 5 years. No statistically significant difference in survival rate was found between conservative (52% at 5 years) and radical treatment of the seventh cranial nerve (43% at 5 years). The incidence of recurrent cancer was 25.7% (25 of 97), of which 88% developed during the first 2 years. We report some of the clinical and histologic factors that can influence the prognosis of the disease.

Surgery or radiotherapy for early stages carcinomas of the glottic larynx.

AIMS AND BACKGROUND: The choice of treatment in limited squamous cell carcinoma of the glottic larynx often depends on individual and tumor factors. Data of the literature clearly show that surgery and radiotherapy tend to give identical results in terms of survival. We examined 196 cases of T1-T2/N0 cancers of the glottic larynx. We review the literature and discuss the indications and the efficacy of the various available treatments. METHODS AND STUDY DESIGN: 196 consecutive cases of T1-T2/N0 cancers of the glottic larynx were examined. In 54.5% the tumor was confined to the vocal cord; in 38.2% it extended to the anterior commissure, in 4.6% to the arytenoid cartilage and in 2.5% to the floor of the ventricle. We performed partial laryngeal surgery in 41.3% (81 cases). Radiotherapy alone was employed in 58.6% (115 cases). RESULTS: In T1a and T1b cases there was no statistically significant difference in 5-year disease-free survival. In T2 cases the NED survival of patients who underwent partial laryngectomies (90% of cases) was significantly better (P <0.05) than among patients given radiotherapy (73%). NED survival at 5 years in patients with the primary tumor on a vocal cord, ventricle or anterior commissure was 78%, 80% and 81%, respectively, with no statistically significant difference among the various sites. It is possible that involvement of the anterior commissure exposes patients to greater risk of recurrence when radiotherapy alone is used (5 out of 23 cases, 21.7%, compared to 3 out of 52 cases, 5.7%, among our surgically treated patients). CONCLUSIONS: When the tumor is confined to the vocal cord and mobility is not impaired (T1a), surgery and radiotherapy give comparable results, and the latter yields a better functional outcome. When the anterior commissure is involved, recurrences appear to be less likely after surgery. In T2 glottic carcinoma, surgery gives better results than radiotherapy alone. In any event, the choice of treatment should be patient-specific and based on a careful analysis of the factors involved in each case.

[Carcinoma of the base of the tongue: a case series]. / I carcinomi della base della lingua: contributo casistico.

A carcinoma of the base of the tongue is diagnosed with difficulty and therapy offers a poor clinical prognosis. Between November 1988 and April 1993 45 patients were evaluated (38 men and 7 women, mean age 60 years). These patients were in poor clinical conditions and advanced clinical stage. Surgical treatment alone or in association with radiotherapy was employed in 17 patients. In the remaining patients radiation therapy alone or associated with chemotherapy was employed. Three-year overall actuarial survival was 39.5% and 3-year NED survival was 21%. Certain prognostic factors were evaluated: T stage, lymph nodes, TNM staging, extension to near anatomical areas and treatment. A Cox multivariate regression analysis revealed that clinical N stage was significant for prognosis (3-year overall actuarial survival was 76.9% for NO and 28% in subjects with clinical nodes). Subjects with neoplasm extension to pharyngo-laryngeal area could have better prognosis and, a finally, patients treated with surgery alone or in association with other treatment would achieve better local control than others.