Nasal cancer

鼻咽癌
  • 文章类型: Journal Article
    鼻前庭鳞状细胞癌(NVSCC)是一种头颈部恶性肿瘤,在临床管理的大多数方面都没有达成共识。本文件的目的是提供最新的建议,其中包括有关其临床特征的最新证据以及近距离放射治疗作为主要治疗方式的高疗效。
    成立了一个工作组,该工作组由意大利耳鼻咽喉头颈外科学会肿瘤学和重建外科科学委员会成员以及近距离放射治疗专家组成。
    就一系列建议达成了共识,提出了鼻前庭的精细解剖学定义,NVSCC的新型T分期系统,和近距离放射治疗作为护理标准,一种新的导管植入方法。
    委员会强调准确分类在临床实践中的关键作用,并鼓励进一步研究以验证新的分期系统并进一步改进治疗策略。在适当的情况下,建议将患者转诊至具有NVSCC近距离治疗经验的中心.
    UNASSIGNED: Squamous cell carcinoma of the nasal vestibule (NV SCC) is a head and neck malignancy for which there is no established consensus on most aspects of clinical management. The purpose of this document is to give updated recommendations that incorporate recent evidence on its clinical characteristics and the high efficacy of brachytherapy as primary treatment modality.
    UNASSIGNED: A working group consisting of the members of the Scientific Committee for Oncology and Reconstructive Surgery of the Italian Society of Otorhinolaryngology Head and Neck Surgery and radiation oncologists expert in brachytherapy was formed to achieve a consensus.
    UNASSIGNED: Consensus was reached on a set of recommendations, proposing a refined anatomical definition of the nasal vestibule, a novel T staging system of the NV SCC, and brachytherapy as standard of care, with a new method for catheter implantation.
    UNASSIGNED: The Committee emphasises the critical role of an accurate classification in clinical practice and encourages further research to validate the novel staging system and further improve treatment strategies. Where appropriate, it is recommended that patients be referred to centres with specific experience in brachytherapy for NV SCC.
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  • 文章类型: Journal Article
    背景:为了评估一个以区域受累为重点的大型鼻窦恶性肿瘤患者队列,复发和肿瘤结果。
    方法:2008年至2019年在我们的三级转诊中心治疗了鼻腔和鼻旁窦恶性肿瘤患者(n=144)。关于患者和肿瘤特征的图表回顾,进行了治疗和长期结局.
    结果:最常见的组织学类型是鳞状细胞癌(SCC)(n=74),腺癌(n=24)和粘膜黑色素瘤(n=18)。66%的患者(n=95)的主要治疗是手术,其中65.8%(n=66)接受了辅助放疗。20例患者(13.8%)最初分期为cN+,7例患者中,pN+状态在组织病理学上得到证实。130例患者中有56例(43.1%)在治愈性治疗后复发,包括9个本地区域(6.9%)和7个孤立的区域复发(5.4%)。在这16例(局部)区域复发的患者中,有12例患有SCC。腺样囊性癌(87.5%)和SCC(65.3%)显示出最佳的长期总生存率。
    结论:区域参与和区域复发很少。由于稀有性和异质性,关于治疗管理的证据很少,导致缺乏临床指南.
    BACKGROUND: To assess a large patient cohort with sinonasal malignancies focusing on regional involvement, recurrence and oncological outcome.
    METHODS: Patients (n = 144) with malignant tumors of the nasal cavity and paranasal sinuses were treated at our tertiary referral center between 2008 and 2019. A chart review on patient and tumor characteristics, treatment and long-term outcome was performed.
    RESULTS: Most frequent histological types were squamous cell carcinoma (SCC) (n = 74), adenocarcinoma (n = 24) and mucosal melanoma (n = 18). Primary therapy was surgery in 66% of patients (n = 95) of which 65.8% (n = 66) received adjuvant radiotherapy. Twenty patients (13.8%) were initially staged as cN + and in seven cases, pN + status was histopathologically confirmed. Fifty-six of 130 patients (43.1%) had a relapse after curative intended therapy, including nine loco-regional (6.9%) and seven isolated regional recurrences (5.4%). Twelve of these 16 patients with (loco-)regional recurrence had SCC. Adenoid cystic carcinoma (87.5%) and SCC (65.3%) showed the best long-term overall survival.
    CONCLUSIONS: Regional involvement and regional recurrence are scarce. Because of rarity and heterogeneity, evidence on therapeutic management is sparse resulting in the lack of clinical guidelines.
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  • 文章类型: Journal Article
    目的:鼻窦腺癌是罕见且异质性的肿瘤,因此仍未得到充分研究。我们的目的是分析临床表现,影响鼻窦腺癌患者生存的结果和因素,在我们的机构治疗。
    方法:回顾鼻窦腺癌患者的临床记录,在三级肿瘤学机构接受治疗(2010年1月至2019年12月)。
    结果:纳入60例腺癌患者,男性优势(54.90%),平均年龄为57.5±14.9岁。腺癌是最常见的鼻窦肿瘤类型,与我们机构以前的报道相反。在大多数患者中,它是在疾病晚期发现的,与初始阶段诊断的患者相比,其生存率显着降低(p<0.029)。肠型腺癌47例,最常见的是结肠亚型(24%)。具有良好/中等组织学分化的肿瘤相对于低分化的肿瘤具有生存优势(p=0.043)。最常见的治疗方式是手术,然后是放疗。在53%的患者中进行了内窥镜切除,在40%的患者中使用了外部方法。估计3年和5年的总生存率分别为64%和53%,分别,癌症特异性生存率分别为72%和65%,在同一时期。复发率为32%,主要发生在局部。3年无病生存率为71%,5年为65%。
    结论:尽管是我们样本中最常见的鼻窦恶性肿瘤,与其他系列相比,鼻窦腺癌仍然是罕见的肿瘤,其局部失败率约为30%。诊断晚期和组织学分化程度对这些肿瘤的预后有负面影响。
    OBJECTIVE: Sinonasal adenocarcinomas are rare and heterogeneous tumors and for this reason remain understudied. Our purpose is to analyze clinical presentation, outcomes and factors affecting survival of patients with sinonasal adenocarcinomas, treated at our institution.
    METHODS: Retrospective review of clinical records of patients with sinonasal adenocarcinoma, treated at a tertiary oncology institution (January 2010 to December 2019).
    RESULTS: Sixty patients diagnosed with adenocarcinoma were included, with male preponderance (54.90%) and a mean age of 57.5±14.9 years. Adenocarcinoma was the most frequent type of sinonasal cancer, contrary to previous reports from our institution. In most patients, it was detected at an advanced disease stage, significantly decreasing their survival rate when compared to patients diagnosed at initial stages (p<0.029). Intestinal type adenocarcinoma was established in 47 patients, the most frequent being the colonic subtype (24%). Tumors with good/moderate histologic differentiation presented a survival advantage over those that were poorly differentiated (p=0.043). The most common treatment modality was surgery followed by radiotherapy. Endoscopic resection was performed in 53% of the patients and an external approach was used in 40% of the patients. Estimated overall survival rates at 3 and 5-years were 64% and 53%, respectively, and cancer specific survival 72% and 65%, for the same period. Recurrence rate was 32% and occurred mainly locally. Disease Free Survival rate was 71% at 3 years and 65% at 5 years.
    CONCLUSIONS: Despite being the most common sinonasal malignancy in our sample, in contrast to other series, sinonasal adenocarcinomas are still rare tumors with a substantial local failure rate of around 30%. Advanced stage at diagnosis and histologic differentiation grade negatively affected prognosis of these tumors.
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  • 文章类型: Multicenter Study
    目的:目的是评估鼻内镜与外用手术治疗鼻窦肠型腺癌(ITAC)的局部肿瘤疗效及复发因素。
    方法:进行了一项回顾性非随机病例对照多中心研究,包括从10个三级转诊中心招募的452个未经治疗的鼻窦ITAC。根据UICC2017(pT)对肿瘤进行重新分类。使用Kaplan-Meier方法获得存活曲线。采用对数秩检验进行单变量分析。采用Cox模型进行多变量分析,校正年龄,T级,和放射治疗。二元逻辑回归比较了手术并发症,并对阳性切缘进行了两项补充分析。
    结果:我们比较了195和257例通过外部和内窥镜手术的患者,分别。平均随访59.2±48.7个月。30.6例患者术后切缘受到侵犯,而18.9%的患者受到侵犯,分别(p=0.007)。总复发率为33.8%和24.6%,分别(p=0.034)。在单变量和多变量分析中,由于更好的手术切缘,内镜方法在局部无复发生存率方面存在显着差异(奇数比=2.01(1.2-3.36)p=0.0087)。内镜组的并发症发生率(比率=3.4(1.79-6.32)p<0.001)明显较低。印戒细胞的组织学阳性显示无复发存活的统计学显著差异(p=0.0028)。
    结论:通过内镜方法对ITAC的肿瘤控制更好,带负边缘和没有印戒细胞,复发的两个独立因素。
    The objective was to assess the local oncological outcomes of endoscopic versus external surgical treatment of sinonasal intestinal-type adenocarcinomas (ITAC) and the factors of recurrence.
    a retrospective non-randomized case-control multicenter study was carried out, including 452 untreated sinonasal ITACs recruited from 10 tertiary referral centers. The tumors were re-classified according to the UICC 2017 (pT). Survival curves were obtained using the Kaplan-Meier method. Univariate analysis was done with the log-rank test. Multivariate analysis was performed with a Cox model adjusted for age, T stage, and radiotherapy. A binary logistic regression compared surgical complications and performed two supplementary analyses on positive margins.
    We compared 195 and 257 patients operated by the external and endoscopic approach, respectively. The mean follow-up was 59.2 ± 48.7 months. Post-operative margins were invaded in 30.6 versus 18.9% of patients, respectively (p = 0.007). The overall recurrence rate was 33.8 versus 24.6%, respectively (p = 0.034). There was a significant difference in favor of the endoscopic approach regarding local recurrence-free survival thanks to better surgical margins in univariate and multivariate analysis (Odd Ratio = 2.01 (1.2-3.36) p = 0.0087). The complication rate (Odds Ratio = 3.4 (1.79-6.32) p < 0.001) was significantly lower in the endoscopic group. The histological positivity of signet-ring cells shows a statistically significant difference in recurrence-free survival (p = 0.0028).
    the oncological control of ITAC is better through the endoscopic approach, with negative margins and the absence of signet-ring-cells, two independent factors of recurrence.
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  • 文章类型: Journal Article
    背景:有效的鼻腔重建需要皮肤和软组织覆盖,软骨或骨骼结构,和粘膜衬里。理想的衬里是薄的,柔韧和血管化,使重建具有挑战性。本文介绍了第一个病例系列,其长期结果是颅骨皮瓣用作鼻重建的内衬。
    方法:使用第二阶段鼻重建计费代码确定了从2007年至2019年接受旁前额皮瓣的患者。使用颅周皮瓣作为衬里的患者,对他们有结果和并发症的数据,已确定。
    结果:66例患者接受了二期鼻腔重建。18例患者使用额头和颅周皮瓣进行内衬重建。皮瓣衬里没有立即的术后并发症。三名患者在放疗后遭受部分重大重建失败。其他并发症包括鼻狭窄和皮肤瘘。
    结论:结合前额旁正中皮瓣,颅周皮瓣作为鼻部重建的内衬是可靠的。它是容易获得和有用的切除与有限的粘膜选择。
    BACKGROUND: Effective nasal reconstruction requires skin and soft tissue cover, cartilage or bone structure, and mucosal lining. Ideal lining is thin, pliable and vascularised, making reconstruction challenging. This paper presents the first case series with long-term outcomes of pericranial flaps used as inner lining for nasal reconstruction.
    METHODS: Patients undergoing paramedial forehead flaps from 2007 to 2019 were identified using second-stage nasal reconstruction billing codes. Patients with pericranial flaps for lining, for whom there were data on resulting outcomes and complications, were identified.
    RESULTS: Sixty-six patients underwent second-stage nasal reconstruction. Eighteen patients had paramedian forehead and pericranial flaps for inner lining reconstruction. The flap lining had no immediate post-operative complications. Three patients suffered partial to major reconstructive failure post radiotherapy. Other complications included nasal stenosis and orocutaneous fistula.
    CONCLUSIONS: Combined with paramedian forehead flaps, the pericranial flap is reliable as inner lining for nasal reconstruction. It is easily accessible and useful in resections with limited mucosal options.
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  • 文章类型: Journal Article
    背景:手术和放疗是目前涉及鼻前庭的恶性肿瘤的治疗选择。根据位置,保留器官的切除并不总是可能的,即使是小肿瘤。明确的放射治疗是一种替代器官保存程序。碳离子束放射治疗提供高度适形的剂量分布和更复杂的生物辐射效应,最终导致优化的正常组织保留和改善的结果。本研究的目的是分析毒性,本地控制(LC),用光栅扫描碳离子放射疗法增强(CIRT-B)结合体积强度调节电弧疗法(VMAT)对鼻前庭癌进行照射后的器官保存生存期(OPS)。
    方法:2015年12月至2021年5月,对21例累及鼻前庭的恶性肿瘤患者行CIRT-B联合VMAT照射,进行回顾性分析。诊断基于组织学发现。共有17例患者患有鳞状细胞癌(SCC),4例患有其他组织学。在这个系列中,10%,67%,24%的患者患有Wang1、2和3期肿瘤,分别。3例患者的MRI表现为病理性颈淋巴结。medianCIRT-B剂量为24Gy(RBE),而中位VMAT剂量为50Gy。所有患有病理性颈淋巴结的患者同时接受了光子(SIB)的整合增强,对病理性淋巴结的中位剂量为62.5Gy。8例患者接受顺铂化疗。所有患者均接受放疗后定期随访。Kaplan-Meier估计用于统计学评估。
    结果:照射后中位随访时间为18.9个月。没有常见的毒性标准5级或4级不良事件。共有20例患者出现主要在皮肤和粘膜上的3级不良事件。随访结束时所有患者均存活。治疗后中位OPS为56.5个月。6个月和24个月的OPS分别为100%和83.3%,分别。所有局部复发均发生在放疗后12个月内。治疗后中位无进展生存期(PFS)为52.4个月。6-,12-,24个月的PFS率为95%,83.6%,74.3%,分别。
    结论:CIRT-B联合VMAT治疗鼻前庭恶性肿瘤是安全可行的,导致较高的局部控制率,因此作为器官保存疗法是一个很好的选择。没有记录到与辐射相关的4级或5级急性或晚期AE。
    BACKGROUND: Surgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons.
    METHODS: Between 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan-Meier estimation was used for statistical assessment.
    RESULTS: The median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively.
    CONCLUSIONS: CIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.
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  • 文章类型: Journal Article
    目的:减少鼻整理术通常是一种面部整形手术,旨在治疗鼻畸形和/或鼻塞患者的功能和美学效果。然而,当应用于鼻金字塔的不同病理时,它具有巨大的潜力,超越单独的化妆品和功能目标。
    方法:我们回顾性分析术前情况,手术图表,以及在我们机构接受不同鼻部疾病的还原性鼻成形术的患者的术后结果。
    结果:在治疗鼻部疾病的不同可能应用中,描述了还原性隆鼻的原理和技术,从鼻中隔穿孔到鼻子的良性和恶性疾病。
    结论:减少鼻整复显示在不同鼻部疾病的治疗目的中起着至关重要的作用,在接近他们的隆鼻外科医生的专家手中代表一种多功能工具。
    方法:不适用。
    OBJECTIVE: Reductive rhinoplasty is generally intended as a facial plastic procedure aiming for functional and aesthetic outcomes in patients affected by nasal dysmorphism and/or obstruction. However, when applied to different pathologies of the nasal pyramid it holds great potentialities, beyond the solo cosmetic and functional objectives.
    METHODS: We retrospectively analyzed preoperative conditions, surgical charts, and postoperative results of patients who underwent reductive rhinoplasty for different nasal diseases at our Institution.
    RESULTS: Principles and techniques of reductive rhinoplasty were described in the different possible applications to the treatment of nasal disease, from nasal septal perforation to benign and malignant diseases of the nose.
    CONCLUSIONS: Reductive rhinoplasty showed to play a crucial role in the curative purpose of different nasal diseases, representing a versatile tool in the expert hand of rhinoplasty surgeons who approach them.
    METHODS: N/A.
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  • 文章类型: Journal Article
    目的:放射治疗是治疗猫鼻窦癌的首选方法。文献中描述了不同的协议,尽管缺乏关于最佳协议的明确共识。这项研究的目的是描述耐受性,用周期性低分割方案治疗的猫的疗效和结果。
    方法:回顾性纳入了一个机构中组织学诊断为鼻窦癌的猫。所有患者均采用周期性低分割方案(“QUAD注射”方案)进行治疗。在48小时内,猫用4Gray(Gy)分四个部分进行处理,两次治疗之间至少6小时,每3-4周重复一次,共3个周期,总剂量为48Gy。
    结果:7只猫符合纳入标准。流鼻涕和打喷嚏是最常见的投诉。通过CT检查,所有猫都表现出疾病的晚期(三只改良的Adams阶段3和四只阶段4)。在六只猫中观察到临床改善。五只猫进行了CT随访;一只有完全反应,两个有部分反应,其中一人病情稳定,一人病情进展。在撰写本文时,两只猫仍然活着,而由于肿瘤相关原因,四只猫被安乐死。中位总生存时间为460天。1年生存时间为80%,2年生存时间为0%。未报告严重急性或晚期毒性。
    结论:这是兽医文献中关于周期性大分割方案的首次报道,该方案可以延长晚期鼻窦癌的猫的生存期。当长期住院可能不利于生活质量时,应考虑在患者中使用它,同时仍提供治疗总剂量的放射治疗。
    Radiation therapy is the treatment of choice for cats with sinonasal carcinomas. Different protocols have been described in the literature, though a clear consensus regarding the optimal protocol is lacking. The aim of the study was to describe the tolerability, efficacy and outcome of cats treated with a cyclical hypofractionated protocol.
    Cats with histologically diagnosed sinonasal carcinomas in a single institution were retrospectively included. All patients were treated with a cyclical hypofractionated protocol (\'QUAD shot\' regime). Cats were treated with 4 Gray (Gy) delivered in four fractions within 48 h, with a minimum of 6 h between two treatments, and repeated every 3-4 weeks for a total dose of 48 Gy in three cycles.
    Seven cats met the inclusion criteria. Nasal discharge and sneezing were the most common presenting complaints. All cats presented with advanced stage of disease with CT examination (three with modified Adams stage 3 and four with stage 4). Clinical improvement was seen in six cats. Five cats had a follow-up CT; one had a complete response, two had partial responses, one had stable disease and one had progressive disease. Two cats were still alive at the time of writing while four were euthanased owing to tumour-related causes. The median overall survival time was 460 days. The 1-year survival time was 80% and the 2-year survival time was 0%. Severe acute or late toxicity was not reported.
    This is the first report of a cyclical hypofractionated protocol in the veterinary literature that can provide prolonged survival in cats with advanced stage sinonasal carcinoma. Its use should be considered in patients when prolonged hospitalisation can be detrimental to quality of life, while still delivering a therapeutic total dose of radiation therapy.
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  • 文章类型: Journal Article
    Epistaxis or nosebleeds (NB) are the most common emergency pathology that otorhinolaryngologists have to deal with. Purpose of the work: to study the prevalence of patients with NB in the otorhinolaryngological departments of hospitals in Moscow from 2003 to 2019. The reports of the heads of the ENT departments of the city clinical hospitals in Moscow were studied. Inclusion criteria were hospitals working with an adult contingent of patients. An approximation analysis was carried out and trend indicators of the prevalence of NB were studied.
    RESULTS: 2003 to 2019 the total number of patients treated in ENT hospitals was 563 189 people, 20 623 (3.7%) patients were treated with NB, of which 52 (0.25%) died. The average age of the deceased was 64.7 years, men are 73.7% more prevalent than women. In 96.2% of patients, epistaxis was a complication of the underlying disease, and in 3.8%, it was regarded as a concomitant condition. In 30.8% of the deceased, NB recurred with the background of malignant lesions of the nose and nasopharynx, in 69.2% - posthemorrhagic anemia aggravated diseases of other organs and systems. Over the past 17 years, there has been a tendency for the growth of treated patients with diseases of ENT organs and patients with nosebleeds by 58.5% and 51.1%, respectively. The studied approximation of the relative prevalence and mortality rates in patients with NB showed that for the period from 2003 to 2019. trend values are practically at the same level with the minimum multidirectional linear dynamics - -0.24% and +0.04%, respectively.
    Носовые кровотечения (НК) являются наиболее частой экстренной патологией, с которой приходится сталкиваться оториноларингологам.
    UNASSIGNED: Изучить распространенность больных с НК в структуре оториноларингологических отделений стационаров Москвы за длительный период времени и на основании полученных данных построить математическую модель данного эпидемиологического процесса с трендовым анализом установленных показателей.
    UNASSIGNED: Изучены отчеты заведующих отделений оториноларингологии городских клинических больниц Москвы. Критерием включения были стационары, работающие со взрослым контингентом больных. Проведен аппроксимационный анализ и изучены трендовые показатели распространенности НК.
    UNASSIGNED: С 2003 по 2019 г. общее число больных, пролеченных в отделениях оториноларингологии, составило 563 189 человек, 20 623 (3,7%) пациента находились на лечении с НК, из них 52 (0,25%) скончались. Средний возраст умерших составил 64,7 года, мужчин на 73,7% больше, чем женщин. У 96,2% больных НК представляло осложнение основного заболевания, а у 3,8% — расценено как сопутствующее состояние. У 30,8% умерших НК рецидивировало на фоне злокачественного поражения носа и носоглотки, у 69,2% — постгеморрагическая анемия усугубила заболевания других органов и систем. За последние 17 лет зафиксирована тенденция увеличения пролеченных больных с заболеваниями уха, горла, носа и пациентов с НК на 58,5 и 51,1% соответственно. Изученная аппроксимация относительных показателей распространенности и летальности больных с НК показала, что за период с 2003 по 2019 г. трендовые значения находятся практически на одном уровне с минимальной разнонаправленной линейной динамикой — –0,24% и +0,04% соответственно.
    UNASSIGNED: Полученные данные свидетельствуют о том, что оториноларингологическая служба стационаров Москвы на сегодняшний день обладает достаточным «запасом прочности» в возможности оказания экстренной помощи больным с носовыми кровотечениями.
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  • 文章类型: Journal Article
    According to the International Agency for Research on Cancer classification, formaldehyde is a human carcinogen that targets the nasal cavity. In humans and rats, inhaled formaldehyde is primarily deposited in the nasal cavity mucosa, metabolized to the less toxic formic acid, and finally excreted into the urine or exhaled. Thus, formaldehyde-induced nasal carcinogenicity may be a direct effect of formaldehyde itself, although the underlying mechanisms remain unclear. With regard to cytotoxicity, degeneration and necrosis of nasal respiratory cells occur in rats after short exposure to formaldehyde. Cell proliferation is increased in the damaged cells, suggesting its critical roles both in the early stages and throughout the entire process of nasal carcinogenicity. Hyperplasia, squamous metaplasia, and dysplasia of the damaged epithelium frequently appear as morphological precursor lesions. With regard to genotoxicity, in addition to DNA-protein crosslinks, oxidative DNA damage also occurs in the exposed nasal mucosal cells. Sustained exposure to formaldehyde may cause nasal carcinogenicity through cytotoxicity and auxiliary genotoxicity. In this review, we discuss adverse outcome pathways through which cytotoxicity can lead to carcinogenicity and the development of integrated approaches for testing and assessment for nongenotoxic carcinogens.
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