|
Clinical analysis and nonsurgical management of 11 dogs with aural cholesteatoma
11例犬耳胆脂瘤的临床分析及非手术治疗
作者：Akihiro Imai, Hirotaka Kondo, Tsunenori Suganuma and Masahiko Nagata
翻译：王帆
Background – Aural cholesteatomas, also called tympanokeratomas, are destructive and expansile growths of keratinizing epithelium that develop in the middle ear. They have been reported sporadically in dogs, and surgery is usually the recommended treatment.
Objectives – To describe the common clinical, radiological and histological findings of cholesteatoma; to report on the outcome of conservative management.
Animals – Eleven dogs (13 ears) with cholesteatomas.
Methods and materials – Medical records were reviewed for dogs diagnosed with cholesteatoma between 2012 and 2018. All dogs had computed tomography (CT) and/or magnetic resonance imaging (MRI) followed by trans-canal endoscopic procedure (TEP) for removal and biopsy of middle ear lesions. Dogs were then treated with in-clinic flushing initially weekly tapered to monthly, as well as at-home ear cleaning and application of topical otic steroid medication, initially daily then tapered to once or twice weekly.
Results – Nine dogs had a history of chronic otitis externa; head tilt or facial paralysis was present in seven and four cases, respectively. Otic examination identified a protruding nodule in seven ears. CT demonstrated soft tissue-like material in 12 bullae and expansion in seven bullae. MRI revealed minimally contrast-enhancing bulla contents in 12 ears. Post-TEP and with maintenance medical treatment, nine ears had no further signs of middle ear disease during a mean follow-up of 27.9 months.
Conclusions and clinical importance – The results suggest that otitis externa may not necessarily precede cholesteatoma in all dogs. MRI appears to be more sensitive than CT for identifying cholesteatomas. Conservative treatment of cholesteatomas could be useful before or as an alternative to surgery.
摘要
背景 – 耳的胆脂瘤,也称鼓膜角质瘤,是角化上皮在中耳的破坏和扩张性增生。犬的病例仅有零星报道,通常建议外科治疗。
目的 – 描述胆脂瘤的常见临床、影像学和组织学表现。报告保守治疗的效果。
动物 – 十一只(13只耳)胆脂瘤患犬。
方法和材料 – 对2012年至2018年诊断为胆脂瘤犬的医疗记录进行回顾性分析。所有犬都进行了计算机断层扫描(CT)和/或磁共振成像(MRI),接着进行耳内镜手术(TEP),以便对中耳病变进行切除和活检。每周在医院冲洗耳道一次,逐渐减少为每月一次;并且在家清洁患耳和外用类固醇耳药,最初每天,然后逐渐减至每周一到两次。
结果 – 9只犬有慢性外耳炎病史,7只出现头倾斜,4只出现面瘫。耳道检查发现七只耳道有突出结节;CT显示12例犬鼓室有软组织样物质蓄积,其中7例鼓室扩张;MRI显示12只耳道至少存在鼓室内容物对比度增强。经TEP治疗和维持治疗后,9只耳道在平均27.9个月的随访期间没有进一步的中耳疾病症状。
结论和临床价值 – 结果提示,所有犬外耳炎不一定先于胆脂瘤发生。对于识别胆脂瘤,MRI似乎比CT更敏感。胆脂瘤的保守治疗可以作为手术前的备选方案。
Introduction
介绍
Aural cholesteatoma is an epidermoid cyst that develops in the middle ear and is composed of keratin debris surrounded by keratinizing stratified squamous epithelium. It has been colloquially described as “skin growing in the wrong place”. The misplaced keratinizing epithelium constantly sheds keratin debris, resulting in gradual enlargement of the cyst and the eventual destruction of the adjacent tissue due to increasing pressure and osteoclastic bone resorption activated by inflammatory chemokines. In dogs, cholesteatoma is regarded as a severe complication of otitis media.The term tympanokeratoma has also been proposed for this condition.
耳胆脂瘤是一种发生于中耳的表皮样囊肿，角蛋白碎片被角化层状鳞状上皮包围而成。它被通俗地描述为“皮肤长在错误的地方”。错位的角化上皮不断脱落角蛋白碎片，导致囊肿逐渐增大，并最终由于炎症趋化因子导致压力增加和激活破骨细胞骨吸收而破坏邻近组织。在犬中，胆脂瘤被认为是中耳炎的严重并发症。鼓膜角质瘤这一术语也被描述这类疾病。
The clinical signs of cholesteatoma in dogs may be nonspecific, including otic discharge, head shaking, rubbing and otic pain. Nasopharyngeal and/or neurological signs also may occur. In humans, early diagnosis of cholesteatoma depends on its identification with otoscopic examination.In veterinary medicine, otoscopy is used to diagnose the condition, although definitive diagnosis requires histopathological examination.Computed tomography (CT) and magnetic resonance imaging (MRI) are considered to be reliable methods for evaluating the middle ear and demonstrating middle ear-related lesions. CT is utilized to better define bony structures and can yield valuable information for the detection of cholesteatoma. MRI is used for more accurate assessment of soft tissue structures and can be a useful tool for the further characterization of soft tissue changes and recognition of potential complications; however, it is not routinely utilized in part because of the relatively high cost.
犬胆脂瘤的临床症状可能是非特异性的，包括耳部分泌物、甩头、摩擦和耳部疼痛。也可能出现鼻咽症状和/或神经症状。在人类中，胆脂瘤的早期诊断依赖于耳镜检查。在兽医学中，耳镜检查被用来诊断这种疾病，但确诊需要组织病理学检查。计算机断层扫描(CT)和磁共振成像(MRI)被认为是评估中耳和显示中耳相关病变的可靠方法。CT被用来更好地定义骨结构，可以为胆脂瘤的检测提供有价值的信息。MRI用于更准确地评估软组织结构，并可作为软组织变化特征表现和识别潜在并发症的有用工具;然而，由于成本相对较高，它并没有被常规利用。
The only curative treatment for canine cholesteatoma reported to date is surgery with total ear canal ablation- lateral bulla osteotomy (TECA-LBO) and ventral bulla osteotomy. The prime objective of surgery for cholesteatoma is to remove all keratinous debris and stratified squamous epithelium; recurrence postsurgery is common in animals.
目前报道的治疗犬胆脂瘤的唯一方法是全耳道消融-外侧鼓泡截骨术(TECA-LBO)和腹侧鼓泡截骨术。胆脂瘤手术的主要目的是清除所有角化碎片和层状鳞状上皮;术后复发在动物中很常见。
To the best of the authors’ knowledge, 15 reports (covering a total of 70 cases) of canine cholesteatoma have been published. Reports in which the diagnosis of cholesteatoma was confirmed by histopathological evaluation in combination with CT and MR imaging are limited. No clinical studies of nonsurgical management for aural cholesteatoma have been reported. The purpose of the present study was to report the main clinical and imaging findings of aural cholesteatoma; and to report on the long-term outcome of a minimally invasive therapeutic approach in 11 dogs.
据作者所知，已经发表了15篇关于犬胆脂瘤的报道(共70例)。通过组织病理学评估结合CT和MR成像确诊胆脂瘤的报道有限。目前尚无非手术治疗耳胆脂瘤的临床研究报道。本研究的目的是报告耳胆脂瘤的主要临床和影像学结果;并报道微创治疗方法在11只犬上的长期结果。
Methods and materials
材料和方法
Case selection and clinical analysis Medical records of dogs diagnosed with cholesteatoma, presented between January 2012 and 2018 at the Synergy Animal General Hospital, Saitama, Japan, were examined to determine the following: (i) if histopathological reports stated the presence of keratinizing epithelium and/or thick lamellar keratin debris in the middle ear; (ii) if CT and/or MRI scanning were performed to identify middle ear disease; (iii) if trans-canal endoscopic procedures (TEPs) under anaesthesia were carried out to remove debris in the middle ear; and (iv) if a minimum follow-up of 12 month duration was possible. Signalment, history, physical examination, video-otoscopy findings, diagnostic imaging, cytological evaluation, aerobic microbial culture results, histopathological features and treatment were reviewed in each case. Dogs were followed up and the outcomes of dogs that did not remain in our direct care were determined by telephone interview between the referring veterinarian and client.
研究人员检查了2012年1月至2018年在日本埼玉市协同动物综合医院诊断为胆脂瘤的犬的医疗记录，以确定以下内容:(i)组织病理学报告是否表明中耳中存在角化上皮和/或厚层状角蛋白碎片;(ii)是否曾进行CT及/或核磁共振扫描以确定中耳疾病;(iii)是否在麻醉下进行了耳内镜手术(TEPs)以清除中耳中的碎片;(iv)是否有可能进行至少12个月的随访。回顾了每个病例的特征、病史、体格检查、视频耳镜检查结果、诊断影像、细胞学评估、需氧微生物培养结果、组织病理学特征和治疗。我们对犬只进行了随访，没有住院护理的犬只的结果由推荐兽医和客户之间的电话采访确定。
Video-otoscopic examination
视频耳镜检查
Ear canal evaluations using a video-otoscope (Karl Storz GmbH & Co. KG; Tuttlingen, Germany, and/or Asuka Medical Inc.; Kyoto, Japan) were conducted both before and during TEPs. An initial examination was performed in conscious dogs to assess if the ear canal was adequately open to enable TEP. If stenosis of the ear canal – due to inflammation and proliferative tissue – blocked otoscope access, topical and/or oral steroids were administered to expand the canal before TEP.
使用视频耳镜进行耳道评估，在TEPs之前和期间都进行了研究。在意识清醒的犬只中进行初步检查，以评估耳道是否充分开放以进行TEP。如果耳道狭窄-由于炎症和增生组织-阻塞了耳道，在TEP前给予外用和/或口服类固醇以扩张耳道。
Imaging with CT/MRI was performed with general anaesthesia. The middle ear and ear canal were evaluated using the video-otoscope and/or a 2.7-mm diameter, zero degree rigid endoscope (Asuka Medical Inc.). To facilitate visualization, the ear canal was lavaged using 3–5f feeding tubes with neutral electrolyzed water (NEW) (Asahi Pretec Corp.; Kobe, Japan).
全身麻醉下行CT/MRI成像。使用视频耳镜和/或2.7毫米直径零度刚性内窥镜，对中耳和耳道进行评估。为了便于观察，耳道用3-5f饲管和中性电解水冲洗(NEW)。
Diagnostic imaging methods
影像诊断方法
Computed tomography scanning was performed under general anaesthesia with Somatom Emotion 16 (Siemens Healthineers Japan; Tokyo, Japan) to investigate the whole skull. Contiguous transverse 1 mm images were obtained before and after intravenous (i.v.) administration of 2.5 mL/kg (612.4 mg/mL) Iopamidol (Oypalomin 300 injection syringe, Fuji Pharma; Toyama, Japan) and were reconstructed using bone and soft tissue algorithms.
在全身麻醉下使用Somatom Emotion 16进行整个头部计算机断层扫描。在静脉注射2.5 mL/kg (612.4 mg/mL) 碘帕醇造影，并使用骨窗软窗算法进行重建。
Magnetic resonance imaging was subsequently performed using Magnetom Essenza 1.5T (Siemens Healthineers Japan). Sagittal T2- weighted [T2W; slice thickness = 3.0 mm, repetition time (TR) = 4,000 ms, echo time (TE) = 91 ms], transverse T2W (slice thickness = 3.5 mm, TR = 4,000 ms, TE = 86 ms), dorsal T2W (slice thickness = 3.0 mm, TR = 4,000 ms, TE = 86 ms), transverse fluid-attenuated inversion recovery (FLAIR; slice thickness = 3.5 mm, TR = 8,500 ms, TE = 104 ms, Inversion time = 2,438.7 ms), transverse T1-weighted (T1W; slice thickness = 3.5 mm, TR = 520 ms, TE = 11 ms) and dorsal T1W (slice thickness = 3.0 mm, TR = 500 ms, TE = 12 ms) were acquired. Additional transverse and dorsal T1W were obtained following i.v. administration of 0.2 mL/kg (0.5 mmol/mL) gadodiamide hydrate (Omniscan 32% i.v. injection syringe, Daiichi-Sankyo; Tokyo, Japan).
随后使用Magnetom Essenza 1.5T 进行磁共振成像。矢状T2-加权[T2W;切片厚度= 3.0 mm，重复时间(TR) = 4,000 ms，回波时间(TE) = 91 ms]，横切T2W(切片厚度= 3.5 mm, TR = 4,000 ms, TE = 86 ms)，背侧T2W(切片厚度= 3.0 mm, TR = 4,000 ms, TE = 86 ms)，横切液体衰减反演恢复(FLAIR;切片厚度= 3.5 mm, TR = 8,500 ms, TE = 104 ms，反演时间= 2,438.7 ms)，横向t1 -加权(T1W;获得切片厚度= 3.5 mm, TR = 520 ms, TE = 11 ms)和背侧T1W(切片厚度= 3.0 mm, TR = 500 ms, TE = 12 ms)。静脉注射0.2 mL/kg (0.5 mmol/mL)钆双胺一水物造影。
TEP for cholesteatoma
胆脂瘤TEP
The TEP was performed in combination with CT and/or MRI examination. Preoperatively, the length, width and depth of the ear canal and middle ear cavity were measured, as well as the distance from the dorsal fold of the ear canal to the tympanic bulla on each CT/MR image of the cases. The dorsal fold (also called auricular projection) by the cartilaginous ridge represents a landmark that separates the vertical and horizontal ear canals.In addition, the type, number, structure, size and distribution of aural lesions were investigated to clarify the anatomical position of lesions within the ear canal.
TEP与CT和/或MRI检查同时进行。术前测量病例CT/MR图像上耳道、中耳腔的长度、宽度、深度，耳道背褶到鼓泡的距离。软骨脊旁的背侧褶皱(也称为耳廓突出)是分隔垂直耳道和水平耳道的标志。此外，还对耳部病变的类型、数量、结构、大小和分布进行了调查，以明确病变在耳道内的解剖位置。
Dogs were positioned in lateral recumbency with the affected side uppermost. Cleaning and flushing the ear canal were conducted with NEW, and any type of obstruction in the external ear canal was removed to access the middle ear. If a protruding nodule in the horizontal ear canal was present, it was grasped with curved mosquito forceps or aural forceps under endoscopic visualization and then removed by a traction–torsion manoeuvre. Residual portions of the nodule were completely removed under endoscopic visualization using 5f biopsy forceps with c.2.5 mm oval cups (Karl Storz GmbH & Co. KG), or vaporized by DLV-20 diode laser (Asuka Medical Inc.). Local irrigation with NEW was used to reduce and control the bleeding. In addition, for cases with stenosis due to proliferative lesions at the bony part of the ear canal, the top of the lesion was vaporized with a diode laser in the same manner as for ablation of residual mass fragments. For all cases, keratinaceous debris was directly removed from the middle ear using the 5f biopsy forceps and samples were placed in 10% formalin for histopathological evaluation separately from the tissues removed from the external ear canal. Impacted keratinaceous debris in the tympanic cavity was then removed by either aural forceps, suction and/or 3–5f feeding tubes under either video-otoscopic or rigid endoscopic guidance. The bulla was lavaged to remove remaining debris with NEW. Finally, 0.1 mL triamcinolone acetonide (Kenacort-A intradermal and intra-articular aqueous suspension infection, 1%, 50 mg/5 mL, Bristol-Myers Squibb; Tokyo, Japan) was administered to the middle ear cavity.
犬侧卧保定，患侧在上。用NEW清洗和冲洗耳道，清除外耳道内任何类型的阻塞，以便进入中耳。如果在水平耳道存在突出的结节，则在内窥镜下用弯曲的蚊钳或耳钳抓住它，然后通过牵引扭转操作将其移除。在内窥镜观察下，使用带c.2.5 mm椭圆杯的5f活检钳或DLV-20二极管激光汽化，完全切除结节残余部分。局部灌洗NEW可减少和控制出血。此外，对于因耳道骨质增生性病变导致狭窄的病例，病变顶部用二极管激光汽化，方法与消融残留肿块碎片相同。所有病例均使用5f活检钳直接从中耳取出角质碎片，并将样本与从外耳道取出的组织分开放置在10%福尔马林中进行组织病理学评估。然后在视像耳镜或刚性内窥镜引导下，用耳钳、吸引泵和/或3-5f饲管清除鼓室内嵌塞的角化碎片。用NEW冲洗鼓泡以清除剩余碎片。最后，中耳腔上药，0.1 mL曲安奈德。
For prophylactic medical management post-TEP, repeated in-clinic tube flushing by a soft feeding tube with NEW was performed in awake dogs once weekly for two to four weeks, followed by tapering to once every two weeks for four weeks and eventually to once monthly. The indication for tapering was based on otic conditions, such as the presence of ear discharge and behaviours including scratching or head shaking. Additionally, routine home cleaning was performed with an ear cleaner (Zymox ear cleanser, Pet King Brands, Inc.; Westmont, IL, USA), and/or Tromethamine-EDTA (TrizEDTA Plus, Dechra; Overland Park, KS, USA) and topical mometasone furoate (Fulmeta, Shionogi & Co., Ltd.; Osaka, Japan) was applied to the dogs as prophylactic management to control canal inflammation. At-home ear cleaning and topical steroid administration was performed once daily for two to four weeks, tapering to once every two days for four weeks, then once to twice weekly. If otitis flared despite prophylactic flushes with NEW and topical steroid drops, dogs were treated with topical and/or systemic antimicrobials determined by clinician preference based on cytological evaluation and culture results.
对于TEP后的预防性药物管理，清醒的犬每周一次用NEW软管反复冲洗耳道，持续2 - 4周，随后逐渐减少到每两周一次，持续4周，最终减少到每月一次。逐渐递减指征是基于耳病表现，如存在耳分泌物和行为，包括抓挠或甩头。此外，患犬在家常规使用洗耳液(Zymox洗耳液)，和/或tris-edta(Dechra)和外用糠酸莫米松，作为预防管理，控制耳道炎症。在家清洗患耳和外用类固醇药物每日一次，持续两到四周，逐渐减少到每两天一次，持续四周，然后每周一次到两次。如果在使用NEW和外用类固醇滴剂进行预防性，仍突发耳炎，则临床医生基于细胞学评估和细菌培养结果，对犬进行外部和/或全身性抗生素治疗。
Ear cytological evaluation and bacterial cultures
耳道细胞学检查和细菌培养
Under general anaesthesia, otic exudate was collected from either the middle ear or the deepest part of the ear canal with 3–5f feeding tubes under video-otoscopic guidance as cytological samples and sterile culture swabs. For cytological evalution, samples were placed onto sterile slides. Then, slides were stained with Microscopic Hemacolor Rapid staining of blood smear (Merck KGaA; Darmstadt,Germany). Each slide was evaluated under a high-power field (*40 and/or 100) for the presence of cocci bacteria, rod-shaped bacteria, keratinized squamous epithelial cells and inflammatory cells. For aerobic bacterial culture and antimicrobial susceptibility testing, swabs were submitted to a diagnostic laboratory (LSI Medience Corporation; Tokyo, Japan). Swabs were inoculated onto sheep blood agar plates which were incubated at 35°C for 24 h. All isolates were identified phenotypically and biochemically. Antimicrobial susceptibility was performed using the broth microdilution method, which determined the minimum inhibitory concentrations of antimicrobial agents according to Clinical and Laboratory Standards Institute guidelines.
在全身麻醉下，在视频耳镜引导下，用3-5f管从中耳或耳道最深处采集耳分泌物，作为细胞学样本和无菌培养拭子。为了进行细胞学评估，样品被放置在无菌载玻片上。然后，用显微血涂片快速染色。每张载玻片在高倍镜下(*40和/或100)下评估是否存在球菌、杆菌、角化鳞状上皮细胞和炎性细胞。为了进行需氧细菌培养和药敏测试，棉签被提交到诊断实验室。将棉签接种到羊血琼脂板上，在35°C下培养24小时。所有分离株均进行表型和生化鉴定。使用微量肉汤稀释法进行抗菌敏感性测试，该方法根据临床和实验室标准协会指南确定了抗菌药物的最低抑制浓度。
Histopathological diagnosis of aural cholesteatoma
耳胆脂瘤组织病理学诊断
Biopsy specimens were fixed in 10% neutral-buffered formalin. Representative trimmed tissues were routinely processed, embedded in paraffin, sectioned at 5 μm and stained with haematoxylin and eosin. The following criteria were used for diagnosis of cholesteatoma: (i) origin of tissue confirmed as the middle ear using the endoscopic procedure; (ii) presence of cornified epithelium and (iii) presence of amorphous thick lamellar keratin debris. A tentative diagnosis of cholesteatoma also was made for cases which satisfied (i) and (iii) but not (ii) (i.e. they lacked cornified epithelium).
活检样本固定在10%中性缓冲福尔马林中。有代表性的切片组织常规处理，石蜡包埋，5 μm切片，苏木精和伊红染色。胆脂瘤的诊断标准如下:(i)经内窥镜检查确认为中耳的组织来源;(ii)存在角化上皮和(iii)存在无定形厚层状角蛋白碎片。对于符合(i)和(iii)但不符合(ii)的病例(即缺乏角化上皮)，也作了胆脂瘤的初步诊断。
Results
结果
Signalment and clinical findings
特征和临床结果
Eleven dogs were included in this study; including French bulldog (n = 5); pug (n = 2), and one each of Chihuahua, Yorkshire terrier, shiba inu and Akita inu. There were two intact males, four castrated males and five spayed females. Ages ranged from 4 to 12 years, with a mean age of 8.2 years (median, 8 years). The durations of clinical signs varied from four to 104 weeks, with a mean duration of 28.1 weeks (median 12 weeks). Two dogs had bilateral disease, and nine dogs had unilateral disease, giving a total of 13 ears.
这项研究包括了11只犬;包括法国斗牛犬(n = 5);巴哥犬(n = 2)，吉娃娃犬、约克夏犬、柴犬和秋田犬各1只。有两只未去势雄性，四只已去势雄性和五只绝已绝育雌性。年龄4 - 12岁，平均8.2岁(中位数8岁)。临床症状持续时间4 ~ 104周不等，平均持续时间28.1周(中位数12周)。2只犬有双侧疾病，9只犬有单侧疾病，共13只患耳。
Nine of the 11 dogs had a history of chronic otitis externa in the affected ears. Five of the nine dogs had a history of recurrent otitis, and four of nine had a history of continuous otitis. Suspected primary causes of otitis externa were atopic dermatitis (two dogs), excessive cerumen (two dogs), foreign body (two dogs) and idiopathic (four dogs). The duration of chronic otitis externa ranged from six months to over five years. Onset of otitis media was suspected from one to 11 months before their presentation. Two of the 11 dogs had no history of chronic otitis externa and were presented for nasopharyngeal and/or neurological signs of possible middle ear disorders.
11只犬中有9只患耳有慢性外耳炎病史。9只犬中有5只有复发性中耳炎病史，9只犬中有4只有持续中耳炎病史。怀疑外耳炎的原发原因是特应性皮炎(2只)、耵聍过多(2只)、异物(2只)和特发性(4只)。慢性外耳炎病程从6个月到5年以上不等。中耳炎在发病前1至11个月被怀疑发病。11只犬中有2只没有慢性外耳炎病史，出现鼻咽和/或可能的中耳疾病的神经症状。
Aural signs included otorrhoea (eight dogs), ear scratching (two dogs) and head shaking (two dogs). During physical examination, neurological signs were identified in nine dogs. Head tilt was present in seven dogs, facial nerve paralysis in four dogs and ataxia in three dogs. Two dogs were reported to have had nystagmus, and one dog was said to have had a seizure, but these signs were not detectable at admission. Two dogs showed an algesic response on palpation of the bulla and temporomandibular joint. Two dogs had increased respiratory noise and/or inappropriate respiratory effort. Concurrent diseases were hypothyroidism (two dogs), spondylopathy (two dogs), pyoderma, urolithiasis, cardiological disease (AVblock), entropion, osteoarthritis and patella luxation (one dog each). Details are reported in Table 1.
耳部症状包括耳分泌物(8只犬)、抓耳(2只犬)和甩头(2只犬)。在体检中，9只犬发现了神经症状。7只犬出现头倾斜，4只犬出现面神经麻痹，3只犬出现共济失调。据报道，两只犬有眼球震颤，一只犬有癫痫发作，但这些症状在入院时没有检测到。两只犬在触诊鼓泡和颞下颌关节时出现痛觉反应。两只犬的呼吸噪音增加和/或不适当的呼吸费力。并发疾病有甲状腺功能减退(2只犬)、脊椎病(2只犬)、脓皮病、尿石症、心脏病(AVblock)、眼睑内翻、骨关节炎和髌骨脱位(各1只犬)。详细信息见表1。
Video-otoscopic findings
视频耳镜结果
In 13 ears, video-otoscopy revealed otic discharge and the TM was not observed. In seven ears (cases 1, 2, 3, 4, 5, 10 and 11) a smooth-surfaced, whitish to pale-pinkish and rounded protruding nodule was detected, occluding the horizontal ear canal (Figure S1 in Supporting Information; Table 1). In four ears (cases 3, 4, 8 and 9), a narrowed horizontal ear canal was observed (Table 1).
13耳经视频耳镜检查发现有耳部分泌物，但未观察到TM。在7只患耳(病例1、2、3、4、5、10和11)中检测到表面光滑、白色至淡粉色的圆形突出结节，堵塞水平耳道(附加资料图S1;4只患耳(病例3、4、8和9)出现水平耳道狭窄(表1)。
Diagnostic imaging findings
影像诊断结果
Computed tomography
CT
Computed tomography imaging was performed in 10 dogs (12 ears). All dogs had soft tissue-like material within the affected tympanic bullae. Absence of air contrast within the middle ear cavity was observed in all affected ears. Enlargement of the middle ear cavity was identified in seven ears, osteoproliferation in seven, lysis of the bulla in six, lysis of the cochlea in six (Figure 1a), sclerosis of the temporal bone in two and mineralization of the inner lining of the bulla in one.
对10只犬(12只患耳)进行计算机断层扫描成像。所有犬的鼓泡内均有软组织样物质。所有患耳均观察到中耳腔内无空气对比。7只患耳中耳腔增大，7只患耳骨增生，6只患耳鼓泡破裂，6只患耳耳蜗破裂(图1a)， 2只患耳颞骨硬化，1只患耳鼓泡内壁矿化。
Four ears, in two pugs and two French bulldogs, were affected by lysis of the petrous temporal bone and bulla expansion was present in three of four ears. Conversely, all dogs (five ears) without expansion of the bulla also were French bulldogs and only one of five had bulla lysis. Only one (Akita inu) of three nonbrachycephalic dogs had both expansion and lysis of the tympanic bulla wall.
两只巴哥和两只法国斗牛犬的四只患耳颞骨岩溶解，四只患耳中的三只出现了鼓泡扩张。相反，所有没有鼓泡扩张的犬(5只患耳)也是法国斗牛犬，只有1 / 5的鼓泡溶解。3只非短头犬中只有1只(秋田犬)鼓泡壁同时扩张和溶解。
Soft tissue-like material occupying the horizontal ear canal was observed in seven ears. In five of the seven ears, linear mineralization within the soft tissue-like material in the external ear canal was observed (Figure 1b) and four of seven ears had bulla osteoproliferation. Enlargement of associated lymph nodes was observed in seven dogs (seven ears), specifically the submandibular lymph nodes, retropharyngeal lymph nodes and parotid lymph node in five, six and one dogs, respectively.
7只耳中有软组织样物质占据水平耳道。7只患耳中有5只患耳在外耳道软组织样物质内观察到线性矿化(图1b)，7只患耳中有4只患耳出现鼓泡骨质增生。7只犬(7只患耳)观察到相关淋巴结肿大，其中5只犬下颌下淋巴结肿大，6只犬咽后淋巴结肿大，1只犬腮腺淋巴结肿大。
Postcontrast CT images were available for two ears. In the images after administration of contrast medium, there was no appreciable contrast enhancement of the tympanic bulla content in either ear. One of the two had an enhancing soft tissue mass occluding the horizontal canal.
两耳均有增强后CT图像。在注射造影剂后的图像中，两耳鼓泡内容物均未见明显增强。其中一例有增强软组织肿块阻塞水平耳道。
Magnetic resonance imaging
磁共振成像
Magnetic resonance imaging was performed in all dogs (13 ears). It revealed the presence of material within the bulla which was isointense to slightly hyperintense relative to brain tissue in 12 ears (Figure 2a) and heterogeneous hyperintense in one ear on T1W images. The mass was heterogeneous hyperintense in nine ears, homogeneous hyperintense in three ears and heterogeneous hypointense in one ear on T2W (Figure 2b) and FLAIR images (Figure 2c). Following contrast administration, contents of the bulla did not enhance in all but one ear. However, the inner lining of the bulla showed some partial enhancement in 11 ears. In addition, contrast enhancement of cochleae was observed in nine ears. Heterogeneous contrast enhancement of the meninges also was observed with severe lysis of the petrous temporal bone in two dogs.
对所有的犬(13只患耳)进行磁共振成像。结果显示，12耳鼓泡内存在与脑组织相关的等强度至微强度高的物质(图2a)， T1W图像显示1耳不均匀性高。T2W上9耳呈不均一性高信号，3耳呈不均一性高信号，1耳呈不均一性低信号(图2b)和FLAIR像(图2c)。对比后，除一只耳外，其余耳鼓泡内内容物均无增加。11耳鼓泡内层部分增强。此外，9只耳的耳蜗均有增强。在两只犬的颞骨岩严重溶解的情况下，也见到脑膜的异质增强。
In eight ears, soft tissue-like material in the external ear canal was enhanced (Figure 2d). Before the injection of contrast medium, the material was isointense to brain tissue in all ears on T1W images, whereas it was heterogeneous hyperintense in five ears, slightly hypointense in two ears and hyperintense in one ear on T2W and FLAIR images.
8耳外耳道软组织样物质增强(图2d)。注射造影剂前，T1W图像上所有耳脑组织均为等强，而5耳为异质性高强，T2W和FLAIR图像上为略低强，1耳为高强。
Cytological evaluation and microbial culture
细胞学评价和微生物培养
Cytological examination of otic discharge was performed in seven ears. Bacterial cocci, rods or a combination of both, were present in four, one and two of seven ears, respectively. Keratinized squamous epithelial cells and neutrophils were identified in four and six of seven ears, respectively. Aerobic bacterial culture of the middle ear was performed in five ears, and all cultures were positive. More than one species of organism was isolated in three ears. Bacteria isolated were Pseudomonas aeruginosa (four of seven ears), group G Streptococcus spp. (two of seven ears), Staphylococcus pseudintermedius group (one of seven ears) and Staphylococcus schleiferi (one of seven ears).
7只患耳进行了耳部分泌物细胞学检查。7只患耳中分别有4只、1只和2只存在细菌球菌、杆菌或两者都有。角质化鳞状上皮细胞和中性粒细胞分别在7只患耳中的4只和6只中有发现。5耳进行中耳需氧细菌培养，均为阳性。在三只患耳中分离出一种以上的生物。分离出的细菌为铜绿假单胞菌(7只患耳中的4只)、G组链球菌(7只患耳中的2只)、假中间葡萄球菌组(7只患耳中的1只)和施氏葡萄球菌(7只患耳中的1只)。
Histopathological findings
组织病理学结果
Tissue samples taken from 10 middle ears demonstrated keratinizing epithelium and keratin debris consistent with cholesteatoma (Figure 3). In the other three middle ears (cases 6, 8 and 11), a tentative diagnosis of cholesteatoma was made because cornified epithelium was not identified.
10只中耳的组织样本显示角化上皮和角蛋白碎片与胆脂瘤一致(图3)。在另外3只中耳(病例6,8,11)中，由于未发现角化上皮，初步诊断为胆脂瘤。
In seven dogs, histopathological evaluation of protruding nodules within the external ear canal (Figure 4) revealed dense fibrous connective tissue surrounded by squamous epithelium. In addition, five of seven had variable degrees of central cores of osseous metaplasia (OM). In Case 1, a markedly abnormal bony architecture was found.
在7只犬中，外耳道内突出结节的组织病理学评估(图4)显示致密的纤维结缔组织被鳞状上皮包围。此外，7例中有5例有不同程度的骨化生中央核。病例1中，发现明显异常的骨结构。
In one of seven ears, histopathological results for a tissue sample taken from the deeper part of the external acoustic meatus exhibited hyperplasia and hyperkeratosis of the epidermis, dermal oedema, fibrosis and lymphocytic infiltration with dilation of ceruminous glands with stasis of secretum.
7只患耳中的1只，从外耳道深层取的组织样本的组织病理学结果显示表皮增生和角化过度，真皮水肿，纤维化和淋巴细胞浸润，耵聍腺扩张，分泌物淤积。
Outcome of TEP
TEP结果
All dogs, except for Case 6, were discharged with pain medication as a postprocedure in TEP. The duration of pain medication varied from one to five weeks. One dog (Case 5) was given Robenacoxib (Onsior, Elanco Japan K.K.; Tokyo, Japan) 2.0 mg/kg orally (p.o.) once daily.Eight dogs were administered prednisolone (Predonine, Shionogi & Co., Ltd.; Osaka, Japan) 0.5–1.0 mg/kg p.o. once daily and one dog (Case 4) was given prednisolone 0.5–1.0 mg/kg p.o. once every other day; then the corticosteroid treatment was tapered down. No serious postprocedural complications were observed in any dogs, except for Case 3 which developed temporary facial nerve paralysis that spontaneously resolved within eight weeks.
除病例6外，所有犬在TEP手术后均使用止痛药物出院。止痛药的持续时间从一到五周不等。一只犬(病例5)服用了罗贝考昔，2.0毫克/公斤口服(p.o.)，每日一次。8只犬注射泼尼松龙，0.5-1.0 mg/kg p.o.，每日一次;1只犬(病例4)给予泼尼松龙0.5-1.0 mg/kg p.o.隔日一次;然后皮质类固醇治疗逐渐减少。除病例3出现暂时性面神经麻痹并在8周内自行缓解外，所有犬均未观察到严重的术后并发症。
Follow-up ranged from 12 to 58 months, with a median follow-up of 29 months (mean, 27.9 months). Post-TEP, in-clinic tube flushing and at-home ear cleaning were performed for all the cases once weekly and once daily, respectively. The frequency of treatment was gradually tapered based on assessment of clinical signs; maintenance treatment of once monthly or twice monthly tube flushing in clinic was performed for six and five dogs, respectively. Routine regular home cleaning was recommended once weekly in five dogs, every other day in one dog and every day in two dogs. The owner of Case 4 declined to continue home cleaning due to difficulties in performing the procedure alone, but monthly in-clinic flushes continued. For all but one dog (Case 4), at-home and in-clinic management continued until the end of the study. In seven ears, glucocorticoid eardrops were applied as a proactive therapy. Initially, three to five drops were applied to each ear once daily. The frequency of administration of topical glucocorticoids was tapered by one half each week to a maintenance frequency of once or twice weekly. For management of chronic aural inflammation, in addition to topical steroid drops, oral oclacitinib was administered to Case 11 after the second TEP and to Case 10 beginning four weeks after the first TEP. For control of concurrent atopic dermatitis, oclacitinib (Apoquel, Zoetis; Parsippany, NJ, USA) was prescribed to Case 9 and oral prednisolone was intermittently administered to Case 6.
随访12 ~ 58个月，中位随访29个月(平均27.9个月)。对所有病例分别进行TEP后、临床导管冲洗和家庭洗耳，每周一次和每天一次。根据临床症状评估逐步减少治疗频次;分别对6只和5只犬进行每月1次或每月2次导管冲洗的维持治疗。5只犬每周进行一次常规家庭清洁，1只犬每隔一天进行一次，2只犬每天进行一次。病例4的宠主拒绝继续进行家庭洗耳，因为单独进行洗耳有困难，但每月门诊冲洗仍在继续。除了一只犬(病例4)外，所有犬的家庭和诊所管理一直持续到研究结束。在7只患耳中，应用糖皮质激素滴耳剂作为积极治疗。最初，每天在每只患耳上滴三到五滴。外用糖皮质激素的频率每周减少一半，维持每周一或两次的频率。对于慢性耳部炎症的管理，除了外用类固醇滴剂外，病例11在第二次TEP后给予口服奥拉替尼，病例10在第一次TEP后4周开始给予口服奥拉替尼。为控制并发特应性皮炎，病例9使用奥拉替尼，病例6间歇性使用口服泼尼松龙。
Nine ears (seven dogs) had no recurrence of middle ear disease in this study. Four ears (four dogs: cases 3, 4, 5 and 11) had recurrent clinical signs after the first endoscopic procedure. The mean time to recurrence was 4.3 months (range: one to 12 months; median: two months). In Case 3, a protruding nodule recurred two months after the initial procedure, despite the dog receiving prophylactic care. As the owners declined otic surgery, a second TEP was immediately performed, and the dog received systemic and topical antimicrobial medication. Recurrence of cholesteatoma was confirmed with histopathological evaluation. No significant aggravation was observed on either CT or MRI findings, except for osteoproliferation in the bony part of both external ear canals. Clinical signs waxed and waned, and then the dog underwent a third TEP for removal of remnants of keratin debris after which clinical signs resolved. In Case 4, ear discharge recurred at one month after the initial procedure. The owners declined an endoscopic or surgical approach, and the dog was managed with only monthly tube flushing. Unfortunately, clinical signs persisted. In Case 5, ear discharge recurred at 12 months after the initial procedure. Clinical signs waxed and waned, and eventually second TEP was performed due to deterioration of signs 25 months after the first procedure. Recurrence of cholesteatoma was confirmed with histopathological evaluation. No significant changes in CT and MRI findings compared to the first procedure were observed. Clinical signs resolved after the second procedure. In Case 11, otitis recurred two months after the initial procedure. The dog received appropriate home cleaning with administration of oclacitinib. Subsequently, otitis resolved.
9耳(7只犬)中耳疾病无复发。4只耳(4只犬，分别为病例3、4、5、11)首次内镜手术后临床症状复发。平均复发时间为4.3个月(范围:1 ~ 12个月;中位数:两个月)。在病例3中，尽管犬只接受了预防性护理，但在初始手术两个月后，一个突出的结节复发。由于主人拒绝了耳部手术，立即进行了第二次TEP手术，并对犬进行了全身和外用抗生素治疗。经组织病理学检查证实为胆脂瘤复发。CT和MRI均未见明显加重，除双外耳道骨质部分增生外。临床症状有增有减，然后进行第三次TEP以去除残余的角蛋白碎片，之后临床症状消失。病例4，初次手术后一个月耳分泌物复发。主人拒绝了内窥镜或手术方法，只对犬进行了每月一次的导管冲洗。不幸的是，临床症状仍然存在。病例5，初次手术后12个月耳分泌物复发。临床症状时好时坏，最终在第一次手术后25个月因症状恶化而进行第二次TEP。经组织病理学检查证实为胆脂瘤复发。与第一次手术相比，CT和MRI结果无明显变化。第二次手术后临床症状消失。病例11，初次手术后两个月中耳炎复发。犬只接受了适当的家庭洗耳，并给予奥拉替尼。随后，中耳炎缓解。
None of the owners reported any adverse effects with regard to the management regimen during this study.
在这项研究中，没有主人报告任何关于管理方案的不良影响。
Discussion
讨论
In the veterinary literature, no significant breed predilection for cholesteatoma has been reported. In this report, over half of the dogs were brachycephalic breeds. Previous reports documented that dysfunction of the auditory tube and the narrow nasopharynx could be predisposing factors for developing primary acquired cholesteatoma. In addition, hypertrophic bulla walls and stenotic bony parts of the horizontal ear canals also could predispose brachycephalic breeds to secondary acquired cholesteatoma.
在兽医文献中，没有明显的胆脂瘤品种倾向性的报道。在这份报告中，超过一半的犬是短头犬。先前的报道表明，咽鼓管功能障碍和鼻咽狭窄可能是发生原发性获得性胆脂瘤的易感因素。此外，鼓泡壁扩大和水平耳道狭窄的骨部分也可使短头犬易患继发性获得性胆脂瘤。
In our study, nine dogs had a history of chronic otitis externa, which can be considered as an important predisposing factor for secondary acquired forms in any breed. However, two of the cases were evaluated for a history of neurological issues, not the typical chronic history of otitis externa. The primary acquired form of cholesteatoma may occur in dogs, although the secondary acquired form appears to be more common.
在我们的研究中，有9只犬有慢性外耳炎的病史，这可以被认为是任何品种继发性获得性耳炎的重要易感因素。然而，其中两个病例被评估为神经系统问题的病史，而不是典型的慢性外耳炎的病史。原发性获得性胆脂瘤可能发生在犬，但继发性获得性胆脂瘤似乎更常见。
Computed tomography scanning plays an important role in the assessment of dogs with middle ear diseases. It has been proposed that a nonenhancing but expansile lesion, which is hyper-attenuating to brain, is likely to be a cholesteatoma. However, expansion of the bulla is not regularly observed. Our study identified expansion of the bulla in 53.8% of the ears and 75% of the brachycephalic breeds with expansile bulla also had lysis of the bulla. By contrast, 80% of the brachycephalic breeds without expansile bulla did not have bulla lysis. In humans, it is hypothesized that cholesteatoma slowly enlarges in the middle ear and gradually erodes adjacent bony structures with activated osteoclasts. Thus, the early stages of cholesteatoma might remain unidentified by CT scanning. Bulla expansion in these breeds could be impeded due to their hypertrophic bulla wall.
计算机断层扫描在犬中耳疾病的评估中起着重要作用。有人提出，一个非增强但扩张的病变，脑组织高度衰减，很可能是胆脂瘤。然而，鼓泡扩张并不常见。我们的研究发现，53.8%的耳鼓泡扩张，75%的短头犬鼓泡扩张也有鼓泡溶解。相比之下，80%没有扩张鼓泡的短头品种没有鼓泡溶解。在人类，据推测，胆脂瘤在中耳缓慢扩大，并逐渐侵袭邻近的骨结构与激活的破骨细胞。因此，早期胆脂瘤可以通过CT扫描来鉴别。这些品种的鼓泡扩张可能由于其扩张的鼓泡壁而受到阻碍。
It was reported, albeit in only one case, that findings on MR imaging included an expansile bulla containing material isointense to brain tissue on T1W and of mixed intensity on T2W images. In addition, material in the bulla was found to show minimal postcontrast enhancement, with enhancement localized to the region immediately adjacent to the bone. In our cases, the bulla contents commonly appeared isointense on T1W images, heterogeneous hyperintense on T2W images and minimally enhanced after contrast injection, with partial enhancement in the location of the inner epithelial lining of the bulla. In humans, the inner component of a cholesteatoma consists of keratin debris that is avascular, so the absence of contrast enhancement of the contents on MR imaging was not unexpected. Furthermore, in humans, vascularity associated with the abnormal epithelium may be increased due to angiogenic growth factors produced by inflammatory cell populations in the matrix and perimatrix of cholesteatoma. Findings of heterogeneous intensity and enhancement on MRI could reflect the histopathological features of cholesteatoma, such as increased vascularity on hyperproliferative epithelium and absent vascularity within keratin debris. Moreover, in humans, it was reported that pre- and postcontrast conventional MRI allows the differentiation of inflammatory mucosa, granulation tissue and cholesteatoma, whereas CT was not able to differentiate between the diseases. Thus, MRI might be a helpful diagnostic tool to ensure accurate and early diagnosis of canine cholesteatoma.
据报道，尽管只有一例，但MR成像结果包括一个扩张的鼓泡，其中含有T1W上与脑组织强度等的物质，T2W上为混合强度。此外，鼓泡内的物质显示出最小的增强，增强仅限于紧邻骨的区域。在我们的病例中，鼓泡内容物在T1W上表现为等强，T2W上表现为不均匀的高强，注射造影剂后表现为轻度增强，鼓泡内上皮内膜位置部分增强。在人类中，胆脂瘤的内部成分由无血管的角蛋白碎片组成，因此MR成像中内容物没有增强是不足为奇的。此外，在人体内，由于胆脂瘤基质和周围炎性细胞群产生的血管生成生长因子，与异常上皮相关的血管可能增加。MRI强度和增强不均能反映胆脂瘤的组织病理学特征，如高增殖上皮血管增多，角蛋白碎片内血管缺失。此外，据报道，在人类中，常规MRI造影前后可以区分炎症粘膜、肉芽组织和胆脂瘤，而CT不能区分这些疾病。因此，MRI可能是一个有用的诊断工具，以确保准确和早期诊断犬胆脂瘤。
For seven of the 11 dogs in this study, a protruding nodule consisting of fibrous connective tissue surrounded by squamous epithelium was found in the external ear canal. Histopathologically, the lesions in dogs appeared to be different in character from typical aural polyps in cats. Presence of ciliated columnar epithelial cells is a prerequisite for the histopathological definition of a polyp, and as a consequence, in terms of terminology, polyp is not an appropriate description for the canal nodules seen in this study. In dogs, the association between the protruding nodules and cholesteatoma remains to be fully elucidated. It has been reported that a pug with cholesteatoma had an external ear canal mass with a thick, keratinizing epithelium. The authors noted that the lesion might be related to the cholesteatoma. In the present study, histopathological evaluation of external ear canal nodules in five cases revealed a core of OM. Likewise, it has been reported in a German shepherd dog with a cholesteatoma in the middle ear, accompanied by a cholesterol granuloma with a core of OM in the horizontal ear canal. OM is a type of ectopic ossification of fibrous connective tissue.
在这项研究中，11只犬中的7只在外耳道中发现了一个突出的结节，由纤维结缔组织组成，周围是鳞状上皮。从组织病理学上看，犬的病变与猫的典型耳息肉特征不同。纤毛柱状上皮细胞的存在是息肉组织病理学定义的先决条件，因此，在术语方面，息肉不适用于本研究中所见的耳道结节。在犬类中，突出结节与胆脂瘤之间的关系仍有待完全阐明。据报道，一只患有胆脂瘤的巴哥犬外耳道有一个厚的角质化上皮肿块。作者认为病变可能与胆脂瘤有关。在本研究中，5例外耳道结节的组织病理学评估显示核心为OM。同样，在一只德国牧羊犬的中耳胆脂瘤中也有报道，同时在水平耳道伴有胆固醇肉芽肿和OM核心。OM是一种纤维结缔组织异位骨化。
Postoperative short-term complications after TEP occurred in only one dog (9.1%) which developed facial palsy. Procedures involving the middle ear potentially can cause facial nerve palsy and cholesteatoma may be attached to vulnerable underlying structures including the facial nerve. In the veterinary literature, facial nerve palsy and dryness of the nostrils was reported postoperatively in two (18.2%) of 11 dogs that underwent surgery for cholesteatoma. In previous retrospective studies of canine TECA and LBO, 13–46% had facial nerve paresis, and 4–23% had residual deficits in facial nerve function after TECA-LBO.
TEP术后短期并发症仅1只(9.1%)出现面瘫。涉及中耳的手术可能会导致面神经麻痹，胆脂瘤可能附着在脆弱的底层结构上，包括面神经。在兽医文献中，11只接受胆脂瘤手术的犬中，有2只(18.2%)在术后出现面神经麻痹和鼻孔干燥。在之前对犬TECA和LBO的回顾性研究中，13-46%的犬出现面神经麻痹，4-23%的犬在TECA-LBO后出现面神经功能残留缺损。
It has been reported that surgical treatment is curative in only 50% of cases of canine cholesteatoma. Recurrence was seen in one of four dogs (25.0%) at 12 months postsurgery in one study and in 10 of 19 dogs (52.6%) at a mean time of 11.3 months in another study. In addition, one study reported that recurrence was suspected in five of 11 dogs (45.5%) at a mean time of 7.5 months. Postsurgical recurrence is likely due to the difficulty of complete surgical removal of abnormal keratinizing epithelium and keratin debris.6 In the present study, clinical signs recurred in four of 11 dogs (four of 13 ears: 30.8%) at a mean time of 4.3 months post-TEP. For these cases, the involved tissues could not be adequately removed from the middle ear with an initial TEP because of their advanced stage. The remnants of cholesteatoma might lead to recurrence sooner. Moreover, even in cases without recurrence after TEP, the possibility remains that residues of cholesteatoma may persist in small cavities of the bulla and keratin accumulation can slowly create clinical signs. Thus, the need to manage ongoing diseases suggests that owners should be prepared for monitoring after TEP, lifelong maintenance therapy and repeated TEP, if necessary.
据报道，手术治疗仅能治愈50%的犬胆脂瘤病例。在一项研究中，4只犬中有1只(25.0%)在术后12个月复发，在另一项研究中，19只犬中有10只(52.6%)在平均11.3个月后复发。此外，一项研究报告，11只犬中有5只(45.5%)在平均7.5个月的时间内怀疑复发。术后复发可能是由于难以完全手术清除异常角质化上皮和角蛋白碎片在本研究中，11只犬中有4只(13只患耳中有4只:30.8%)的临床症状在TEP后平均4.3个月复发。对于这些病例，由于其晚期，无法通过初始TEP从中耳充分移除患病组织。胆脂瘤残余可能导致复发更快。此外，即使在TEP后没有复发的情况下，胆脂瘤残留物仍有可能存在于鼓泡的小腔内，角蛋白的积累可以慢慢产生临床症状。因此，对正在发生的疾病进行管理的需要表明，宠主应准备好进行TEP、终身维持治疗和必要时重复TEP后的监测。
As part of maintenance therapy, oclacitinib was used in three cases in this study. In Case 9, oclacitinib was prescribed for concurrent atopic dermatitis. The other two dogs (cases 10 and 11) had unilateral chronic otitis without any cutaneous lesions or identifiable primary disease. Oclacitinib is presumed to inhibit both proallergic and proinflammatory cytokines (IL-2, 4, 6, 13 and 31) as a specific JAK1 and -3 inhibitor. Although it is an extra-label indication, we prescribed oclacitinib to the latter two dogs in an attempt to treat the chronic aural inflammation, which seems to play a fundamental role in multiple aetiopathogenic mechanisms of acquired cholesteatoma.Additionally, it is suggested in humans that the IL-6/ STAT3 signalling pathway is active and may play an important role in the epithelial hyperproliferation of acquired cholesteatoma. During this study, the clinical signs were managed with no relapse in the dogs treated with oclacitinib. More study is necessary to elucidate the efficacy and risk of oclacitinib as a component of postprocedural management in canine cholesteatomas.
作为维持治疗的一部分，本研究中有3例患犬使用了奥拉替尼。在病例9中，为并发的特应性皮炎使用奥拉替尼。另外两只犬(病例10和11)为单侧慢性中耳炎，无任何皮肤病变或可识别的原发疾病。据推测，奥拉替尼作为一种特异性的JAK1和JAK-3抑制剂，可以抑制促过敏和促炎症细胞因子(IL-2, 4,6,13和31)。虽然这是一种标签外适应症，但我们为后两只犬使用了奥拉替尼，试图治疗慢性耳部炎症，这似乎在获得性胆脂瘤的多种病因机制中起着根本作用。此外，在人类中，IL-6/ STAT3信号通路是活跃的，可能在获得性胆脂瘤的上皮过度增生中发挥重要作用。在这项研究中，使用奥拉替尼治疗的犬的临床症状得到了控制，没有复发。需要更多的研究来阐明奥拉替尼作为犬胆脂瘤术后管理的一个组成部分的有效性和风险。
In the present study, around 70% of ears were treated successfully by a single TEP, followed by maintenance treatment involving daily to weekly ear cleaning at home and weekly to monthly tube-flushing in the clinic. Likewise, it was reported that the condition in a dog was controlled by removal of keratin debris from the bulla under video-otoscopic guidance, although the dog died from unrelated causes 29 months later. We suggest that conservative treatment of cholesteatoma by TEP with regular removal of the inflammatory stimulus in the middle ear could be useful before or in place of surgery.
在本研究中，约70%的患耳通过单次TEP治疗成功，随后进行维持治疗，包括每日至每周在家清洗患耳，每周至每月在诊所导管洗耳。同样，据报道，一只犬的这种疾病是通过在视频镜下从鼓泡中去除角蛋白碎片来控制的，但这只犬在29个月后死于无关的病因。我们建议保守治疗胆脂瘤的方法是在手术前或手术后定期去除中耳的炎症刺激。
Limitations in the evaluation of TEP in this study include its retrospective nature, the small sample size, the referral nature of the population and the lack of objective criteria to define treatment outcome. In the future, a largescale prospective controlled cohort study should be conducted to conclusively evaluate therapeutic outcomes.
本研究评价TEP的局限性包括其回顾性、样本量小、病例的转诊性质以及缺乏客观的标准来定义治疗结果。在未来，应该进行大规模的前瞻性对照队列研究，以结论性地评估治疗效果。
In conclusion, chronic otitis externa may not necessarily precede acquired cholesteatoma in dogs but the presence of a protruding nodule in the external canal may be a significant predictor of cholesteatoma and the use of MRI can facilitate the early diagnosis of this disease. Nonsurgical therapy is not curative as surgery may be; however, early conservative treatment of cholesteatoma could be an effective option before or as an alternative to surgery, even though it requires long-term at-home and in-clinic maintenance care.
综上所述，慢性外耳炎可能并不一定先发于犬获得性胆脂瘤，但外耳道中明显结节的存在可能是胆脂瘤的一个重要预测因素，MRI的使用可以促进这种疾病的早期诊断。非手术治疗不像手术可以治愈。然而，胆脂瘤的早期保守治疗可能是手术前或手术替代的有效选择，即使它需要长期的家庭和临床维护护理。
Figure 1. Computed tomography lesions of aural cholesteatoma of dogs.
(a) At the level of the tympanic cavity, soft tissue-like material fills the left tympanic bulla, creating enlargement, lysis and osteoproliferation of the tympanic bulla wall, with lysis of the cochlea (Case 7). (b) At the level of the tympanic cavity, a soft tissue mass appeared in the right external ear canal with mineralization in the centre (Case 1). Soft tissue-like material also fills the right tympanic bulla, causing mild enlargement of the tympanic bulla wall.
图1。犬耳胆脂瘤的计算机断层扫描。
(a)鼓室水平，软组织样物质填满左侧鼓泡，造成鼓泡壁增大、溶解、成骨增生，并导致耳蜗溶解(病例7)。(b)鼓室水平，右侧外耳道出现软组织肿块，中心矿化(病例1)。右侧鼓泡也填满软组织样物质，导致鼓泡壁轻度增大。
Figure 2. Magnetic resonance images (MRIs) of aural cholesteatoma of a dog at the level of the tympanic cavity (Case 7).
(a) T1-weighted, (b) T2-weighted, (c) fluid-attenuated inversion recovery and (d) postcontrast T1-weighted transverse MRIs. The expansile left bulla includes material isointense to brain tissue on T1-weighted images and heterogeneous hyperintense on T2-weighted and fluid-attenuated inversion recovery. On postcontrast T1-weighted images, partial enhancement is identifiable, particularly in the inner lining of the left bulla, whereas the contents of the left bulla are not significantly enhanced.
图2。犬耳胆脂瘤在鼓室水平的磁共振图像(病例7)。
(a) t1加权，(b) t2加权，(c)液体衰减反转恢复和(d)对比后t1加权横向mri。扩张的左鼓泡包括t1加权图像上脑组织的物质等强，以及t2加权和液体衰减反转恢复上的不均匀高强。在t1加权增强后，可见部分强化，尤其是左鼓泡内层，而左鼓泡内内容物未见明显强化。
Figure 3. Photomicrograph of the histopathological findings of canine aural cholesteatoma (Case 7).
Section of the cholesteatoma wall constituted a multilayered squamous epithelium lining a cystic lumen filled with abundant lamellar eosinophilic keratin debris. Haematoxylin and eosin stain, *20.
图3。犬耳胆脂瘤组织病理学的显微照片(病例7)。
胆脂瘤壁呈多层鳞状上皮排列，囊腔内充满大量层状嗜酸性角蛋白碎片。苏木精和伊红染色，*20。
Figure 4. Gross appearance of a protruding nodule in the ear canal of a dog (Case 1).
A whitish to pinkish, oval and pedunculated nodule was removed by the traction–torsion manoeuvre
图4。犬耳道中突出结节的肉眼外观(病例1)。
一例白色至粉红色，椭圆形，带蒂结节经牵引扭转术清除。
Figure S1. Video-otoscopic appearance of a protruding nodule in the external ear canal of a dog (Case 2).
图S1。犬的外耳道有一个突出的结节(病例2)。 | 
|Archiver|手机版|小黑屋|宠医帮
( 京ICP备2022012070号-2 ) 
发表于 2023-6-16 12:15:39
收藏
转播
分享
淘帖
楼主