2021年唾液腺恶性肿瘤两种国际指南的解读与比较

为给唾液腺恶性肿瘤(salivary gland malignancy,SGM)的诊疗提供循证建议,2021年美国临床肿瘤学会和美国国家综合癌症网分别制订和更新了SGM临床实践指南。本文从SGM的术前评估、手术治疗、放射治疗、系统性治疗、随访和复发转移性疾病诊疗等角度出发,对两种指南进行解读和比较分析,旨在为我国SGM的诊疗提供临床指导。     

唾液腺恶性肿瘤患者血清免疫抑制酸性蛋白的检测及其临床意义

目的：探讨免疫抑制酸性蛋白（ＩＡＰ）检测在唾液腺恶性肿瘤中的临床意义．方法：采用单向免疫扩散法检测了２６例唾液腺恶性肿瘤患者及３０例正常对照的血清ＩＡＰ．结果：正常人血清ＩＡＰ含量为３４６±１０７μｇ／ｍｌ,唾液腺恶性肿瘤患者血清ＩＡＰ为６８１±１６３μｇ／ｍｌ,两者相比有显著性差异（ｐ＜０．０１）;肿瘤患者的ＩＡＰ阳性率高达８８．５％（２２／２６）,Ⅲ～Ⅳ期患者血清ＩＡＰ水平明显高于Ⅰ～Ⅱ期患者（ｐ＜０．０１）,随着临床分期的增加,ＩＡＰ水平也随之增高;治疗后血清ＩＡＰ水平明显下降（ｐ＜０．０１）．结论：检测唾液腺恶性肿瘤患者血清ＩＡＰ有助于监视病情的发展,观察疗效及判断预后．     

2002—2013年上海市唾液腺恶性肿瘤流行情况分析

目的:分析上海市2002—2013年唾液腺恶性肿瘤的人群发病状况,阐明疾病在本地区的流行病学特点。方法:根据上海市疾病预防控制中心提供的唾液腺恶性肿瘤病例资料,通过数据重新核实,采用SPSS 17.0软件包统计唾液腺恶性肿瘤的发病率、性别比、年龄分布状况、解剖部位占比以及病理分布情况;采用年均变化百分比、 χ²检验和Fisher精确检验,比较年度之间的变化情况。结果:2002—2013年,上海市共诊断唾液腺恶性肿瘤新发病例2 308例,发病粗率为13.93/100万,标率为8.54/100万,性别比为1.08∶1;中位首诊年龄为58岁。12年间,发病率变化平稳。唾液腺恶性肿瘤中,1/3来自小唾液腺,其中1/3来自腭腺;大唾液腺的发病比为12∶3∶1。黏液表皮样癌、腺样囊性癌和非特异性腺癌是最常见的3大病理类型。结论:目前上海市唾液腺恶性肿瘤的发病率较低,但不同部位、不同病理类型的好发人群差异较大,提示发病危险因素存在差异,值得关注。     

口腔颌面部恶性肿瘤治疗指南

口腔颌面部恶性肿瘤约占全身恶性肿瘤的3%～5%,其组织病理学类型多样,以鳞状细胞癌最多见,约占90%以上。由于解剖部位特殊,口腔颌面部恶性肿瘤不仅影响外观,而且造成咀嚼、吞咽、呼吸和语音等功能障碍,严重降低患者的生存质量,并危及生命。手术、放疗和化疗是治疗口腔颌面部恶性肿瘤的3大治疗手段,免疫治疗、生物治疗对某些类型的肿瘤和晚期患者是必要的补充和辅助措施。早期患者以手术治疗为主,晚期患者则提倡综合序列治疗,并鼓励患者参加临床试验。口腔颌面部恶性肿瘤患者的5年总生存率在65%左右,晚期患者的5年生存率不足30%。为了规范口腔颌面部恶性肿瘤的治疗,进一步提高患者的远期生存率,中华口腔医学会口腔颌面外科专业委员会肿瘤学组牵头,组织国内从事口腔颌面部恶性肿瘤治疗的知名专家,参考国内外文献,尤其是2009年美国NCCN指南中的相关内容,撰写了《口腔颌面部恶性肿瘤治疗指南》,希望对口腔颌面部恶性肿瘤的规范治疗起到指导作用。随着医学科学技术的发展,新的技术、方法、药物会不断出现,本指南将及时予以更新,以反映和纳入最新的研究成果,为广大患者提供最新的治疗方案。     

姜黄素调控唾液腺肿瘤细胞增殖和凋亡的机制探讨

目的: 探讨姜黄素靶向miR-155-5p/TP53INP1轴诱导氧化应激调控唾液腺肿瘤细胞增殖和凋亡的机制。方法: A253细胞加入姜黄素及转染miR-155-5p mimic和（或）pcDNA3.1-TP53INP1,共同培养。采用CCK-8法检测细胞增殖;流式细胞术检测细胞凋亡;划痕实验检测细胞迁移能力;双荧光素酶报告实验验证miR-155-5p与TP53INP1之间的靶向关系;qRT-PCR检测细胞miR-155-5p、TP53INP1mRNA的表达;Western印迹法检测细胞TP53INP1、Caspase8、Caspase3、Bcl-2、Bax蛋白表达;ELISA法检测细胞SOD、Gpx、MDA含量。采用SPSS 22.0软件包对数据进行统计学分析。结果: 双荧光素酶报告实验证实,TP53INP1是miR-155-5p的下游靶向调控分子;与DMSO组相比,姜黄素组细胞凋亡、Caspase8、Caspase3、Bax蛋白表达及TP53INP1表达显著增加,Bcl-2蛋白表达、miR-155-5p mRNA及划痕迁移细胞数显著降低（P<0.05）;与姜黄素+miR-155-5p mimic组相比,姜黄素+pcDNA3.1-TP53INP1组、姜黄素+miR-155-5p mimic+pcDNA3.1-TP53INP1组细胞凋亡、Caspase8、Caspase3、Bax蛋白表达显著增加,Bcl-2蛋白表达显著升高（P<0.05）,姜黄素+pcDNA3.1-TP53INP1组SOD、GSH-PX活性及划痕迁移细胞数显著降低,MDA含量显著升高（P<0.05）。结论: 姜黄素抑制A253细胞增殖,促进A253细胞凋亡,其机制可能与靶向miR-155-5p/TP53INP1轴诱导氧化应激调控有关。     

唾液腺多形性腺瘤中透明质酸的表达与作用

目的 观察透明质酸在唾液腺腺体和唾液腺多形性腺瘤中表达,探讨透明质酸与唾液腺多形性腺瘤发生的关系。方法 收集2020～2022年唾液腺多形性腺瘤蜡块21例及同一患者冻存唾液腺腺体和多形性腺瘤组织8例。Real-time PCR检测冻存唾液腺腺体组织和多形性腺瘤中透明质酸合成酶（hyaluronan synthase, HAS）、透明质酸酶（hyaluronidase, HYAL）基因表达。筛选高表达基因相对应的蛋白,通过免疫组织化学染色和Western Blot检测蛋白表达。结果 Real-time PCR检测HYAL2、HAS2和HAS3在唾液腺腺体和多形性腺瘤中呈高表达。唾液腺腺体中HYAL2表达为HAS3表达的20倍,差异显著（P<0.05）。唾液腺多形性腺瘤中HAS2、HAS3和HYAL2无统计学差异（P>0.05）。免疫组织化学染色显示多形性腺瘤中HAS2、HAS3表达增高,与HYAL2表达具有明显差异（P<0.05）。唾液腺组织中HYAL2高表达,与HAS2和HAS3表达差异显著（P<0.05）。Western Blot灰度值分析显示HAS2、HAS...     

唾液腺透明细胞癌的诊断与治疗

目的：探讨唾液腺透明细胞癌的诊断和治疗原则。方法：2002年8月-2007年1月间共收治唾液腺透明细胞癌11例,均行手术扩大切除。3例有颌骨破坏者,分别行上颌骨次全切除、双侧上颌骨部分切除和下颌骨节段性切除,5例颈淋巴结肿大者行颈淋巴清扫术,对术后软硬组织缺损采用不同方法修复,5例辅以术后放疗。结果：11例术后病理均为唾液腺透明细胞癌,4例颈淋巴结转移。透明细胞免疫组化CK均（＋）,S-100均（-）,9例SMA（-）。除1例前臂皮瓣部分坏死外,11例伤口均愈合良好,无其他并发症。所有患者术后已随访0.5～5a,未发现局部肿瘤复发、颈淋巴结和远处转移。结论：唾液腺透明细胞癌是一种少见的唾液腺低度恶性肿瘤,免疫组化检查有助于确诊治疗首选局部广泛切除,颈淋巴结转移者应行颈淋巴清扫术,术后放疗主要用于局部复发或颈淋巴结转移者,患者一般预后良好。     

“口腔颌面部恶性肿瘤治疗指南”发布

<正>《中国口腔颌面外科杂志》2010年第2期全文发表了由中华口腔医学会口腔颌面外科专业委员会肿瘤学组牵头制订的"口腔颌面部恶性肿瘤治疗指南"(通信作者:张陈平、郑家伟,作者:郑家伟、李金忠、涂文勇、张陈平、郭传瑸、李龙江、孙沫逸、韩正学、廖贵清、潘潮斌、张文峰、季彤)。     

“口腔颌面部恶性肿瘤治疗指南”发布

近日出版的《中国口腔颌面外科杂志》全文发表了由中华口腔医学会口腔颌面外科专业委员会肿瘤学组牵头制订的“口腔颌面部恶性肿瘤治疗指南”（通信作者：张陈平、郑家伟,作者：郑家伟、李金忠、涂文勇、张陈平、郭传殡、李龙江、孙沫逸、韩正学、廖贵清、潘朝斌、张文峰、季彤）。     

唾液腺纤维肉瘤的临床与病理分析——附2例报告

目的报告2例唾液腺罕见纤维肉瘤。方法对2例唾液腺纤维肉瘤患者的病史、诊断、治疗、病理特征与预后,进行报告与分析。结果原发于腮腺1例术后4周化疗,随访至今仍存活。原发于颌下腺1例术后4月死亡。结论纤维肉瘤极少发生于唾液腺,但恶性程度较高,应提高警惕。     

Minor salivary gland secretion in children and adults

The minor salivary glands are of great importance in the physiology and pathology of the oral cavity. So far, studies of the minor glands have concentrated on adults. In the present study, minor salivary gland secretion was studied in the buccal and labial mucosa of 3-year-old children, adolescents and young adults. In addition, the number of glands per surface area was assessed in the labial mucosa. A total of 90 individuals were included, 30 in each age-group. Saliva was collected on filter paper discs and the salivary secretion rate was measured using a Periotron 8000. The number of secreting labial glands was assessed on PAS-stained filter paper discs under a microscope. Salivary secretion in the buccal mucosa was found to be age-related, with a statistically significant lower rate of secretion (P=0.003) in the 3-year-olds (mean 7.7 microl x cm(-2) x min(-1)) compared with the young adults (11.9 microl x cm(-2) x min(-1)). No significant differences between the sexes were noted. For the labial glands, no age- or sex-related differences were found. In all age-groups, salivary secretion was significantly higher in the buccal than in the labial mucosal area. A statistically significant difference in number of secreting glands was found between all age-groups, with a decreasing number of glands per surface unit with age. The number of glands was significantly lower in males compared with females in the group of adults. The lower rate of buccal salivary secretion in the young children may imply that the oral mucosa is more vulnerable to external injury and that caries protection on the buccal molar surfaces is lower. Previous studies indicate that adults with a reduced rate of minor salivary gland secretion are more susceptible to caries.     

Apoptosis-associated protein expression in human salivary gland morphogenesis

ObjectiveSalivary gland (SG) development is based on branching morphogenesis, in which programmed cell death has been proposed to play a role in cell signalling and organ shaping. In the mouse salivary gland apoptosis has been suggested to play a key role in lumen formation, removing the central cells of the epithelial stalks. Here we analyse the expression of several anti- and pro-regulators of apoptosis during human SG development in a range of developmental stages.DesignFoetal SGs obtained from the University of São Paulo were analysed by immunohistochemistry to assess the expression of apoptosis-associated proteins: caspases (caspase-6, -7, -9 and cleaved caspase-3), Bcl-2 family members (Bax, Bak, Bad, Bid, Bcl-2, Bcl-x and Bcl-xL), Survivin (BIRC5), Cytochrome C and Apaf-1.ResultsNuclear expression of Bax and Bak was identified in presumptive luminal areas at initial stages, while Bcl-xL showed the most relevant anti-apoptotic activity. Caspase-6, -7 and -9 were expressed during all stages, while interestingly cleaved caspase-3 showed no prominent expression, indicating that caspase-7 is the main effector. Apoptosome complex components Apaf-1 and Cytochrome C, as well as survivin were all positive in developing glands.ConclusionsThe particular expression pattern of several apoptotic regulators in human SG development suggests the existence of a fundamental role for apoptosis during duct formation. The absence of Bad and Bid expressions indicates that the instrinsic pathway is more active then the extrinsic during human gland formation. The subcellular localisation of intrinsic-apoptosis proteins correlated with apoptotic activity, but also suggested additional non-apoptotic functions.     

Innervation and myoepithelial arrangements in the submandibular salivary gland of ferret investigated by enzyme, catecholamine and filament histochemistry

Although the submandibular gland of ferret is useful for studying salivary secretory processes which are regulated by nerves and involve myoepithelial activity, little attention has been paid to its parenchymal innervation and myoepithelial arrangements. Therefore, glands obtained postmortem from mature ferrets of both sexes were here examined with the use of light-microscopic histochemical techniques for cholinesterases, phosphatases and phosphorylase, histofluorescence for catecholamines, and milling dyes. Acetylcholinesterase staining was associated with nerve trunks in the interlobular stroma and an extensive intralobular network of nerve fibres, presumably of a cholinergic type, embracing acini and ducts. There were fewer fibres containing fluorescing catecholamines, presumably adrenergic. They were largely associated with acini. Numerous stellate cells with fine branching processes embracing acini, presumably myoepithelial cells, and a few spindle-shaped basal cells, investing striated ducts, were demonstrated on frozen tissue by alkaline phosphatase, but not by adenosine triphosphatase, inosine diphosphatase and phosphorylase. Cells of similar shape and distribution were also demonstrated by staining with milling dyes on fixed tissues, indicating possibly a filamentous constituent conferring mechanical stability and/or contractile ability. Together, these results suggest, firstly, that a cholinergic-type parenchymal innervation is prominent in the submandibular gland of ferret, although many adrenergic nerves are also present, and, secondly that the gland has a very extensive myoepithelial network which is possibly involved in membrane transport, and the support and/or contraction of the secretory parenchyma.     

1612例老年唾液腺肿瘤构成比分析

目的:了解老年人唾液腺肿瘤疾患的构成现状,为临床早期诊断和治疗提供依据。方法:回顾分析我科2000年1月—2009年12月10年间(21c10s)老年人唾液腺肿瘤住院患者的临床资料,并与20世纪90年代(20c90s)、80年代(20c80s)统计数据进行比较。结果:伴随着老年口腔颌面-头颈肿瘤患者住院人数的迅速增加,老年唾液腺肿瘤患者总数亦呈明显上升趋势,尤其是良性肿瘤患者数量快速上升。沃辛瘤首次成为最常见的老年唾液腺良性肿瘤。恶性肿瘤中,腺样囊性癌继续位居首位,而癌在多形性腺瘤中上升为第3位,并位居腮腺恶性肿瘤之首。小唾液腺良、恶性肿瘤构成比接近1∶1;而腭腺良、恶性比例倒置为1.34∶1。腮腺区发病仍最多见,其次为腭腺和下颌下腺。女性患者构成比有下降趋势。结论:21c10s老年唾液腺肿瘤构成现状与20c90s及20c80s资料有所不同,临床诊治工作中应注意其相应变化。     

唾液腺多形性腺瘤恶变108例临床病理分析

目的:研究唾液腺多形性腺瘤恶变的临床病理特点。方法:回顾分析上海交通大学医学院附属第九人民医院口腔颌面外科1993年1月至2005年5月间唾液腺多形性腺瘤恶变病例的病理与临床资料。结果:108例唾液腺多形性腺瘤恶变病例,男68例,女40例,男女比为1.7∶1;年龄28～92岁,60～70岁最好发(29例),其次为50～60岁(22例)、70～80岁(20例)和40～50岁(19例)。发生于腮腺者68例,腭部20例,下颌下腺15例,其他部位包括唇、咽旁小唾液腺等。恶变成分主要为腺癌(26例),其次为肌上皮癌(19例),黏液表皮样癌(6例,包括低、中、高度恶性),腺样囊性癌(4例),其他有腺鳞癌、上皮-肌上皮癌、腺泡细胞癌、唾液腺导管癌、鳞癌等。5例发生颈部淋巴结转移,约占4.6%,其原发灶的恶变成分主要为腺癌。结论:唾液腺多形性腺瘤恶变多见于中老年男性,好发于腮腺,其次为下颌下腺和腭部,恶变成分多为腺癌和肌上皮癌;发生颈淋巴结转移者,恶变成分多为腺癌。     

bFGF及其受体FGFRS在成年大鼠唾液腺中的免疫组化定位和mRNA表达

目的 本文研究碱性成纤维细胞生长因子[basic fibroblast growth factor(bFGF)]和成纤维细胞生长因子受体1、2、3和4(FGFR1、FGFR2、FGFR3和FGFR4)在大鼠唾液腺中分布及表达特点。方法 应用免疫组化和RT-PCR的方法研究bFGF和FGFR1，FGFR2，FGFR3和FGFR4在成年大鼠腮腺和颌下腺中的免疫组化定位和mRNA表达。结果 bFGF和FGFR1，FGFR2，FGFR3和FGFR4在成年大鼠腮腺和颌下腺的各级腺管上皮细胞均有较强的特异性免疫染色。在成年大鼠腮腺和颌下腺可以检测到bFGF和FGFR1，FGFR2，FGFR3mRNA表达。结论 成年大鼠腮腺和颌下腺是合成、分泌bFGF的重要源泉。     

Effects of hyperleptinemia in rat saliva composition,histology and ultrastructure of the major salivary glands

ObjectiveTo study the effect of the satiety hormone, leptin, in saliva proteome and salivary gland histology and ultrastructure.DesignIncreases in blood leptin levels were induced through mini-pump infusion in male Wistar rats, during a period of 7 days. Saliva was collected before and at the end of the experimental period, for proteomic analysis, and major salivary glands were collected, at the end, for biochemical, histological and ultrastructural analysis.ResultsImmunohistochemistry revealed the presence of leptin receptors in major salivary glands. Salivary amylase levels and enzymatic activity were decreased in saliva, whereas the enzymatic activity of this protein was increased in the cytosol of parotid gland cells. Transmission electron microscopy allowed the observation of high number of electron-dense granules in cytosol of parotid acinar cells, from leptin treated animals.ConclusionsIncreased levels of plasmatic leptin result in changes in saliva composition and salivary glands function. To our knowledge, this is the first study providing evidences for a potential role of leptin in salivary gland secretion and saliva composition. An understanding of how appetite/satiety factors influence saliva composition and how this composition influences food processing in mouth may be relevant in understanding ingestivebehaviour.     

Endothelin expression in salivary gland

The present paper reviews the roles of endothelin (ET) in the rat submandibular gland (SMG). ET and its mRNA are expressed in the granular convoluted tubule (GCT) segment by immunostaining and in situ hybridization, respectively. ET is synthesized in granular cells of the GCT segment, stored in secretory granules, and secreted into the oral cavity. It is well known that granular cells in the GCT segment of the SMG in mice and rats express many kinds of growth factor such as epidermal growth factor and nerve growth factor. These growth factors are discharged into saliva and thought to regulate oral-esophageal and gastrointestinal mucosa. ET acts as a potent vasoconstrictor with mitogenic property and is excreted from Weibel-Palade bodies in vascular endothelial cells. ET in the salivary origin may regulate its own functions as noted in the endothelial origin. This review deals with comparative discussion of ET and other growth factors, which originate from GCT segments in rodents.