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IntroductionThe study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area.MethodsPatients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided.ResultsA total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher.ConclusionRecurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.

Introduction: Paranasal sinus fungus ball (PSFB) is a non-invasive mycosis, which appears in immunocompetent patients, along with unilateral lesion. The purpose of this study was to analyse various symptoms of PSFB and its radiological, pathological, and microbiological findings. In addition, this study involved the investigation of the incidence of bacterial coinfection and surgical techniques applied for this infection and to report the modern developments in this domain. Materials and Methods: This retrospective study was carried out on 40 consecutive patients referring for PSFB treatment to the Ear, Nose, and Throat Department in San Luigi Gonzaga University Hospital, Turin, Italy, from April 2014 to 2017. Pertinent literature was reviewed and compared within the specified period. All patients were examined by preoperative computed tomography (CT) scan, and 26 (65%) patients were subjected to magnetic resonance imaging (MRI). Results: Totally, 33 patients (82.5%) were affected with single sinus infection, whereas most of the cases suffered from maxillary sinusitis. With regard to CT scan findings, microcalcifications were found in 32.5% of the cases; however, mucosal membrane thickening around the fungus ball (FB) was visible in contrast-enhanced CT scans. According to MRI examination, FB showed a characteristic “signal void” on T 2(42.3%). Only 7(17.5%) patients had a positive mycological culture, whereas bacterial coinfections were identified in 47.5% of the cases. Out of 40 patients, 3(7.5%) subjects had only radiological evidence of fungal colonization while having no histopathological evidence. No patient received postoperative antifungal drugs, and there were no serious complications with only one recurrence. Conclusion: Endoscopic endonasal surgery is the treatment of choice for patients with PSFB receiving no associated local or systemic antifungal therapy. A histopathological study facilitates the confirmation of the diagnosis and exclusion of the invasive form of fungal rhinosinusitis.

International audience; 4,15-Diacetoxyscirpenol (DAS) is a mycotoxin primarily produced by Fusarium fungi and occurring predominantly in cereal grains. As requested by the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed the risk of DAS to human and animal health related to its presence in food and feed. Very limited information was available on toxicity and on toxicokinetics in experimental and farm animals. Due to the limitations in the available data set, human acute and chronic health-based guidance values (HBGV) were established based on data obtained in clinical trials of DAS as an anticancer agent (anguidine) after intravenous administration to cancer patients. The CONTAM Panel considered these data as informative for the hazard characterisation of DAS after oral exposure. The main adverse effects after acute and repeated exposure were emesis, with a no-observed-adverse-effect level (NOAEL) of 32 lg DAS/kg body weight (bw), and haematotoxicity, with a NOAEL of 65 lg DAS/kg bw, respectively. An acute reference dose (ARfD) of 3.2 lg DAS/kg bw and a tolerable daily intake (TDI) of 0.65 lg DAS/kg bw were established. Based on over 15,000 occurrence data, the highest acute and chronic dietary exposures were estimated to be 0.8 and 0.49 lg DAS/kg bw per day, respectively, and were not of health concern for humans. The limited information for poultry, pigs and dogs indicated a low risk for these animals at the estimated DAS exposure levels under current feeding practices, with the possible exception of fattening chicken. Assuming similar or lower sensitivity than for poultry, the risk was considered overall low for other farm and companion animal species for which no toxicity data were available. In consideration of the similarities of several trichothecenes and the likelihood of co-exposure via food and feed, it could be appropriate to perform a cumulative risk assessment for this group of substances.

International audience; Moniliformin (MON) is a mycotoxin with low molecular weight primarily produced by Fusarium fungi and occurring predominantly in cereal grains. Following a request of the European Commission, the CONTAM Panel assessed the risk of MON to human and animal health related to its presence in food and feed. The limited information available on toxicity and on toxicokinetics in experimental and farm animals indicated haematotoxicity and cardiotoxicity as major adverse health effects of MON. MON causes chromosome aberrations in vitro but no in vivo genotoxicity data and no carcinogenicity data were identified. Due to the limitations in the available toxicity data, human acute or chronic health-based guidance values (HBGV) could not be established. The margin of exposure (MOE) between the no-observed-adverse-effect level (NOAEL) of 6.0 mg/kg body weight (bw) for cardiotoxicity from a subacute study in rats and the acute upper bound (UB) dietary exposure estimates ranged between 4,000 and 73,000. The MOE between the lowest benchmark dose lower confidence limit (for a 5% response-BMDL 05) of 0.20 mg MON/kg bw per day for haematological hazards from a 28-day study in pigs and the chronic dietary human exposure estimates ranged between 370 and 5,000,000 for chronic dietary exposures. These MOEs indicate a low risk for human health but were associated with high uncertainty. The toxicity data available for poultry, pigs, and mink indicated a low or even negligible risk for these animals from exposure to MON in feed at the estimated exposure levels under current feeding practices. Assuming similar or lower sensitivity as for pigs, the CONTAM Panel considered a low or even negligible risk for the other animal species for which no toxicity data suitable for hazard characterisation were identified. Additional toxicity studies are needed and depending on their outcome, the collection of more occurrence data on MON in food and feed is recommended to enable a comprehensive human risk assessment.

Deoxynivalenol (DON) is a mycotoxin primarily produced by Fusarium fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain-based products were main sources, whereas in farm and companion animals, cereal grains, cereal by-products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. Since 3-Ac-DON and 15-Ac-DON are largely deacetylated and DON-3-glucoside cleaved in the intestines the same toxic effects as DON can be expected. The TDI of 1 μg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group-TDI for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group-ARfD of 8 μg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group-TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.

Nowadays endoscopic skull base reconstruction is safely and effectively performed by means of two-dimensional (2-D) endoscopic technique. The aim of our study is to compare our 2-D experience with the novel 3-D technology in the field of skull base reconstruction techniques. In this study four patients treated with various kinds of planned duraplasty are included. The new 3-D technology was compared with the high-definition 2-D scopes during the different steps of the procedures. The 3-D endoscopic skull base reconstruction obtained primary closure without complications in all cases. According to the subjective opinion of experienced endosurgeons, this novel technique improved depth perception, distance and size estimation, ability to identify specific anatomic structures, and hand-eye coordination. The main drawbacks detected were inferior sharpness, contrast and lighting that impaired the application of the technique in narrow sinonasal spaces. According to our preliminary impressions, 3-D endoscopic skull base reconstruction is an effective and safe procedure and could represent a significant advantage for accurate managing of the skull base region.

Intestinal-type adenocarcinoma (ITAC) is a rare and locally aggressive occupation-related tumor. Currently, endoscopic-assisted resection and advances in irradiation modalities (3D conformal radiotherapy/intensity-modulated radiation therapy [IMRT]) are emerging as an alternative to traditional open surgery and conventional radiotherapy.Retrospective analysis of 30 consecutive patients affected with sinonasal ITAC, primarily treated by an endoscopic approach followed by 3D conformal radiotherapy/IMRT at a single institution, from 2003 to 2010.The 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and recurrence-free survival (RFS) were 72.7% ± 9.6%, 78% ± 9.5%, 67.9% ± 10.7%, and 69.2% ± 9.4%, respectively (mean follow-up, 48 months). No major complications or serious toxicities were observed. Prognostic factors were stage of disease at diagnosis, development of recurrences, status of surgical margins, grading, tumoral pattern of growth, and proliferative index (Ki-67).The low morbidity of endoscopic approaches, the acceptable toxicity of modern irradiation modalities, and these promising survival rates, indicate that this treatment strategy might be considered a safe, minimally invasive, and maximally effective option for treating selected sinonasal ITAC.

The palatovaginal or pharyngeal artery is a small branch of the internal maxillary artery supplying the nasopharynx. Bleeding from this artery is exceptional and only one case of traumatic epistaxis from this artery has been reported previously. We report a case of a 66-year-old male presenting with right recurrent posterior epistaxis. Endoscopic dissection of the pterygopalatine fossa and direct visualization of the palatosphenoidal canal permitted to identify the origin of bleeding, and coagulation of the pharyngeal artery solved the epistaxis. Although rare, intractable posterior epistaxis may arise from the pharyngeal artery. The anatomical knowledge of this artery and of the palatosphenoidal canal is of outmost importance in endoscopic transpterygoid and nasopharyngeal procedures, to identify the vidian canal, evaluate nasopharyngeal cancer spread in the pterygopalatine fossa, reduce bleeding during surgery of the nasopharynx, and harvest adequately the pedicle of the nasoseptal flap.

To describe the different surgical techniques for nasopharyngeal endoscopic resection (NER) and to support the efficacy of the endoscopic endonasal approach in the management of selected primary and locally recurrent nasopharyngeal tumors (NPTs).Case series with chart review.Patients affected by NPTs who underwent NER from 1997 to 2011 at two Italian referral centers.NER was tailored to the NPT extension and classified as follows: type 1 NER, resection of the posterior nasopharyngeal wall; type 2 NER, resection superiorly extended to the sphenoid; type 3 NER, trans-pterygoid approach to the postero-lateral nasopharynx with removal of pterygoid plates and Eustachian tube, under control of parapharyngeal-petrous-cavernous segments of the internal carotid artery.Thirty-six consecutive patients with primary (9 cases) or locally recurrent (27 cases) NPTs were enrolled. The lesions were staged as follows: stage I, 16 (44.4%); stage II, 3 (8.4%); stage III, 15 (41.6%); and stage IVA, 2 (5.6%). Type 1 NER was performed in 6 cases, type 2 NER in 12, type 3 NER in 16, and bilateral-extended type 3 NER in 2. No perioperative mortality or major complications were observed. Postoperatively, 11 patients received intensity-modulated radiotherapy, with or without chemotherapy. Follow-up ranged from 2 to 173 months (mean: 38 months). Five years overall, disease-specific, and disease-free survivals were 75.1% ± 9.13%, 80.9% ± 7.79%, and 58.1% ± 14.8%, respectively.NER is a feasible and minimally invasive surgical approach for the management of selected primary and locally recurrent NPTs. Our preliminary outcomes are promising, with local control rates comparable to those of conventional procedures. Larger case series and longer follow-up are needed to validate the reproducibility and efficacy of the technique.