Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes

Objective: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints. Methods: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-betal, Fibroblast growth factor-2 and Plate let-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff(R)-11), in culture or in nude mice. Human native menisci were assessed as reference. Results: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9 were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation. Conclusions: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights rese

Salvage surgery after radiotherapy for laryngeal cancer : From endoscopic resections to open-neck partial and total laryngectomies

Objective: To evaluate our experience in management of radiotherapy failure using endoscopic resection (ER) with carbon dioxide laser, open-neck partial laryngectomy (ONPL), and total laryngectomy. Design: Retrospective medical record review. Setting: Referral university hospital. Patients: Seventy-one patients with laryngeal cancer previously treated with radiotherapy (69 patients) and chemoradiotherapy (2 patients) underwent salvage surgery. Interventions: The treatment policy encompassed ER for glottic rT1a, rT1b with limited anterior commissure involvement, and rT2 with normal cord mobility carcinoma. All ONPLs were performed for rT1 and rT2 tumors with suboptimal endoscopic exposure, rT2 tumors with impaired cord mobility or transcommissural extension, and rT3 tumors for limited paraglottic space invasion or involvement of the inner portion of the thyroid cartilage. Total laryngectomy was planned in patients who were not suitable for partial laryngectomy owing to poor general condition, for rT3 carcinoma with massive involvement of the paraglottic space, and for rT4a tumors. Main Outcome Measures: Clinical, radiologic, surgical, and pathologic data. Survival curves were calculated using the Kaplan-Meier method. Comparisons between different variables were performed using the log-rank test. Results: Salvage surgery consisted of ER in 22 patients, ONPL in 15, and total laryngectomy in 34. The pT category after salvage surgery was pT1 in 12 patients, pT2 in 20, pT3 in 20, and pT4a in 19. Five-year diseasespecific and disease-free survival and laryngeal preservation for the entire series were 72%, 61%, and 40%, respectively. Conclusions: Survival rates for the entire series were not different from those previously reported using a more aggressive surgical approach without attempts at organ preservation. The laryngeal preservation rate justifies conservative treatment in the presence of limited recurrent lesions

Narrow-band imaging : a new tool for evaluation of head and neck squamous cell carcinomas: review of the literature

Head and neck squamous cell carcinoma of the upper aerodigestive tract is well known for its frequently late presentation and diagnosis at an advanced stage. In addition, it is well recognized that it may arise in multiple sites, either synchronously or metachronously. Thus it should be imperative to endoscopically screen the upper aerodigestive tract of patients at risk for head and neck squamous cell carcinoma with a new diagnostic tool, especially due to the fact that early lesions are very difficult to detect even by multiple passes with a standard endoscopy, if they are < or = 1 cm in diameter. Lugol chromoendoscopy, which is mainly used in the oesophagus, is not suitable for the head and neck region due to severe mucosal irritation. Herein, narrow-band imaging is described, a diagnostic tool already proved as a useful screening method in other endoscopic fields, and its application in the early detection of head and neck squamous cell carcinoma is reviewed, as reported by previous studies in the otolaryngologic literature. Narrow-band imaging relies on the principle of depth of penetration of light, with the narrow-band blue light having a short wavelength (415 nm) penetrating into the mucosa and highlighting the superficial vasculature. Furthermore, the blue filter is designed to correspond to the peak absorption spectrum of haemoglobin to enhance the image of capillary vessels on surface mucosa. Thus, superficial mucosal lesions that would be missed by regular white light endoscopy, are identified, in view of their neoangiogenetic pattern of vasculature, using the blue light of the narrow-band imaging. Narrow-band imaging has been used extensively in the lower aerodigestive system, yet there are only 2 reports of applications in the region of the head and neck, specifically the oropharynx and the hypopharynx. However, these are not the only sites that can benefit from narrow-band imaging. Herewith, the uses and importance are highlighted of narrow-band imaging as a future diagnostic tool in otolaryngology, in the pre-, intra- and post-operative settings

Transoral laser surgery for recurrent glottic cancer after radiotherapy: oncologic and functional outcomes = La chirurgia transorale nel trattamento del carcinoma glottico dopo fallimento di radioterapia: risultati oncologici e funzionali

Primary radiotherapy (RT) has been successfully employed for treatment of early glottic cancer for the past half century. However, local recurrences still occur in 5-35% of patients. Salvage options for persistent/recurrent glottic cancer include total laryngectomy, open neck partial laryngectomies (ONPLs) and transoral laser surgery (TLS). We performed a retrospective chart review of 35 patients with glottic squamous cell carcinoma previously submitted to RT and managed by TLS at the Department of Otorhinolaryngology - Head and Neck Surgery of the University of Brescia, Italy, from 1995 to 2009. Oncologic outcomes were estimated using the Kaplan-Meier method, and separately calculated for the entire cohort of patients (n = 35) and for patients with true persistent/recurrent disease (n = 30), thus excluding the second primary tumours (n = 5). Hospitalization time and complications were obtained by chart review. Functional outcomes of a subgroup of 10 patients in terms of speech and swallowing were analyzed by the Voice Handicap Index (VHI), GRBAS scale, Multi Dimensional Voice Program (MDVP), M.D. Anderson Dysphagia Inventory (MDADI) questionnaire, videoendoscopy (VEES), and videofluoroscopy (VFS) of swallowing (both graded according to Donzelli's scale), and compared to a cohort of 10 patients matched for age, gender and pT category, treated by the same team of surgeons by TLS as a primary treatment. The types of resection used were: 18 Type III, 1 Type IV, and 16 Type V cordectomies. Postoperative staging was 16 rpT1a, 17 rpT2, and 2 rpT3. The 5-year overall survival for the entire series was 91%. Five-year disease-specific survival, local control with laser alone, and organ preservation rates were 94%, 84% and 87%, respectively. Among the variables tested by univariate analysis, for the entire cohort of patients the pT category had a statistically significant impact on local control with laser alone. Anterior transcommissural extension had a borderline statistical impact on disease-specific survival, while it was clearly significant on overall survival. The status of surgical margins and presence of recurrence after TLS statistically influenced both organ preservation and local control with laser alone. The mean values of VHI, MDADI, and MDVP did not show any statistically significant difference between irradiated and non-irradiated patients. The same was true for GRBAS, VEES, and VFS. This series confirms that TLS after RT failure can be considered a successful surgical option in selected early recurrences, with functional outcomes comparable to those observed after TLS as a primary treatment, and much better than those classically described after ONPLs

Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort

Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient’s family history was considered as potentially BRCAassociated. Patients or disease characteristics were examined using the c2 test or Fisher’s exact test for qualitative variables and the Student's t-test or ManneWhitney test for continuous variables, as appropriate. Results: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/ gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P ¼ 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations. Conclusion: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives. Key words: germline BRCA, epidemiology, pancreatic cancer genetics, familial cance

Post conjunction detection of β\beta Pictoris b with VLT/SPHERE

With an orbital distance comparable to that of Saturn in the solar system, \bpic b is the closest (semi-major axis $\simeq$\,9\,au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to \bpic have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters. We aimed at further constraining \bpic b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. We used SPHERE at the VLT to precisely monitor the orbital motion of beta \bpic b since first light of the instrument in 2014. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6\,au) and prevented further detection. We redetected \bpic b on the northeast side of the disk at a separation of 139\,mas and a PA of 30$^{\circ}$ in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of $a = 9.0 \pm 0.5$ au (1 $\sigma$), it definitely excludes previously reported possible long orbital periods, and excludes \bpic b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.Comment: accepted by A&

Comprendre les comportements face à un risque modéré d’inondation. Etude de cas dans le périurbain toulousain (Sud-Ouest de la France)

Les espaces urbanisés soumis à des risques modérés d’inondation pour les vies humaines sont souvent peu considérés dans les études sur la vulnérabilité aux risques naturels en dépit des enjeux qu’ils représentent en termes de gestion de crise. Comment les riverains y font-ils face au danger et quelles sont leurs « bonnes raisons » d’agir? A partir de l’étude socio-géographique de deux inondations récentes (2000 et 2003) dans la périphérie toulousaine (Sud-Ouest de la France), nous montrons que les caractéristiques de l’aléa dans les vallées étudiées influencent les représentations du risque et par conséquent les motivations à se protéger. Face au risque majeur, la vulnérabilité sociale se trouve ainsi augmentée. Pour améliorer la résilience des populations, il convient d’adapter la communication sur les risques: personnaliser l’information, améliorer la compréhension de l’événement vécu et mobiliser de nouvelles formes de médiation entre gestionnaires et riverains