Pharmacology of drugs used to treat osteoarthritis in veterinary practice

As in humans, pain in animals may be associated with a wide range of conditions and circumstances, ranging from acute trauma to joint diseases. Joint diseases are common in companion animal medicine (horse, dog, cat) and at least 80% of cases are classified as osteoarthritis (OA). Several drug classes are available for OA therapy, including corticosteroids, non-steroidal antiinflammatory drugs (NSAIDs), agents with potential disease modifying properties and nutraceuticals. For long-term maintenance OA treatment, particularly in the horse and dog, NSAIDs are routinely and extensively used. This review outlines the pharmacokinetics (PK) and pharmacodynamics (PD) of NSAIDs in companion and farm animal species. NSAID PK and PD have been studied in models of acute inflammation, which enable use of PK-PD modeling to facilitate (a) studies of mechanism of action at the molecular level and (b) prediction of dosages for clinical use. The PK-PD approach is a powerful but underutilized tool which also facilitates inter-species comparisons.     

Contribution of DOG1 expression to the diagnosis of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, and the majority contain KIT or PDGFRA-activating mutations. However, up to 10% of GISTs are c-kit-negative. Antibodies with increased sensitivity and specificity for the detection of c-kit-negative GIST cases may be of value, especially because some of these cases may also benefit from tyrosine kinase inhibitor therapy.     

The Use of Simvastatin for the Prevention of Gallstones in the Lithogenic Prairie Dog Model

Background: Surgery for morbid obesity is rapidly increasing. Patients undergoing bariatric surgery are prone to gallstone development during the rapid weight loss. These patients are often given medications such as ursodeoxycholic acid to prevent gallstone formation; however, these medications are often poorly tolerated by patients, who subsequently discontinue them. We performed a study in a lithogenic animal model to assess the effectiveness of a potential alternate medication for gallstone prevention. Methods: 20 male prairie dogs were randomly separated into 2 groups and fed a lithogenic diet for 28 days. The study group animals were given 2.5 mg of the HMG-CoA reductase inhibitor simvastatin. Total cholesterol and triglycerides were measured and an open cholecystectomy was performed on each animal at the conclusion of the study period. The gallbladder was visually inspected for gallstones and microscopic biliary cholesterol crystal formation. Results: There was a decrease of 36% in the total cholesterol of the study animals compared to controls. The animals treated with simvastatin showed gallstone formation in 5/10 (50%) of animals, compared with 6/10 (60%) of control animals. The study animals demonstrated microscopic cholesterol crystal formation in 80%, identical to the number found in the control animals. Conclusion: Despite a reduction in cholesterol, simvastatin prevented neither gallstone formation nor biliary cholesterol crystals in this animal model. Given the rapid increase in the number of bariatric surgical procedures coupled with the poor tolerance of ursodeoxycholic acid, viable alternatives should continue to be sought for these patients.     

伊马替尼停药后复发胃肠道间质瘤的临床特征与KIT/PDGFR基因突变分析

目的 探讨转移性胃肠道间质肿瘤(GIST)患者术后伊马替尼辅助治疗过程中,停药与复发的关系,以及KIT第11外显子突变的患者复发后,对伊马替尼的敏感性研究和预后监测. 方法 对GIST患者复发前后临床特征进行分析比较;利用免疫组织化学的方法 辅助诊断和分析复发前后CD117,CD34等GIST细胞标志物的表达情况;采用基因测序的方法 进行KIT/PDGFR基因突变检测. 结果GIST患者术后,规范伊马替尼治疗3年,停药后1年余腹部包块证实为GIST复发;患者KIT 基因第11外显子检测出有缺失突变：c.1667_1672delAGTGGA,提示该患者仍然对伊马替尼敏感;对于诊断GIST,DOG1比CD34更敏感. 结论 伊马替尼的连续用药延长无进展生存时间及延缓GIST复发,DOG1具有比CD34更好的敏感性,更加适合作为GIST的诊断标记物.     

CD117阴性胃肠道间质瘤的临床病理及超微结构

目的:探讨CD117阴性胃肠道间质瘤(gastrointestinal stromal tumours,GISTs)的临床病理及超微结构特征。方法:采用HE、免疫组化(EnVision法)及电镜技术观察16例CD117阴性GISTs。结果:16例患者中11例男性,5例女性,年龄32-67岁,平均54岁。随访9例,1例死亡。组织学形态可分为梭形细胞为主型、上皮样细胞为主型以及梭形和上皮样细胞混合型三类。肿瘤细胞免疫组化阳性表达为DOG1 81.2%(13/16),CD117 0%(0/16),CD34 63%(10/16),Des 6%(1/16),α-SMA 31.3%(5/16),S-100 12.5%(2/16)。电镜下GISTs的超微结构特点与卡哈尔细胞相似。结论:CD117阴性GISTs可通过免疫标记DOG1及电镜检测做出诊断。     

CD117阴性胃肠道间质瘤的临床病理及超微结构

目的：探讨CD117阴性胃肠道间质瘤（gastrointestinal stromal tumours,GISTs）的临床病理及超微结构特征。方法：采用HE、免疫组化（EnVision法）及电镜技术观察16例CD117阴性GISTs。结果：16例患者中11例男性,5例女性,年龄32-67岁,平均54岁。随访9例,1例死亡。组织学形态可分为梭形细胞为主型、上皮样细胞为主型以及梭形和上皮样细胞混合型三类。肿瘤细胞免疫组化阳性表达为DOG1 81.2%（13/16）,CD117 0%（0/16）,CD34 63%（10/16）,Des 6%（1/16）,α-SMA 31.3%（5/16）,S-100 12.5%（2/16）。电镜下GISTs的超微结构特点与卡哈尔细胞相似。结论：CD117阴性GISTs可通过免疫标记DOG1及电镜检测做出诊断。     

DOG1在胃肠道间质瘤中的表达及其临床意义

目的：探讨 DOG1在胃肠道间质瘤（GIST）中的表达及其临床意义。方法：免疫组化 Envision 法对73例 GIST 和26例非 GIST 间叶源性肿瘤检测 DOG1的表达,分析 DOG1与 GIST 的各项临床病理参数之间的关系。结果：在73例 GIST 中 DOG1、CD117和 CD34的阳性率分别为91．78％、94．52％和91．78％,而在26例非GIST 中阳性率为11．54％、3．85％ 和23．08％,以上指标在两组间的表达有统计学差异（P ＝0．000）;DOG1检测 GIST 灵敏度和特异度分别为91．80％、88．50％,而 DOG1联合 CD117检测 GIST 灵敏度和特异度分别为98．60％和84．60％,灵敏度最高;DOG1的表达与 GIST 的性别、年龄、肿瘤的位置、肿瘤的大小、核分裂象和恶性潜能分级等临床病理因素无相关性（P ＞0．05）,同时 DOG1的表达与 GIST 的预后也无相关性（P ＞0．05）。结论：在 GIST 的诊断中 DOG1与 CD117一样是敏感而特异的指标,尤其是对 CD117阴性的 GIST 的诊断中,能够起很好的补充作用,但不能作为评价 GIST 预后的指标。     

A case of successful detection of disseminated gastrointestinal stromal tumors by ascites smear cytology using cell block preparation with DOG1 immunostaining

Cytological features of gastrointestinal stromal tumors (GISTs) have been reported, especially regarding fine‐needle aspiration cytology, including immunostaining for c‐kit and DOG1. Meanwhile, cytological findings of GISTs on ascites cytology have rarely been reported, which may be owing to the rare appearance of GIST tumor cells in ascites. Herein, we present a 66‐year‐old woman who had disseminated GISTs in the abdomen. The GIST tumor cells appeared sparsely in the ascites smear cytology using ascites obtained at the time of autopsy. Even when widespread intra‐abdominal dissemination takes place, GISTs may be hard to detect in ascites smear cytology, based on the experience of this case. However, immunohistochemistry of DOG1 using a cell block preparation was found to clearly visualize the GIST tumor cells, although they were sparsely present. Immunostaining of c‐kit did not provide as clear an identification of the tumor cells as DOG1 did. When suspicious about GISTs, it is wise to prepare a cell block to make it possible to visualize the tumor cells immunohistochemically. Diagn. Cytopathol. 2016;44:137–140. © 2015 Wiley Periodicals, Inc.     

GEIS guidelines for gastrointestinal sarcomas (GIST)

Gastrointestinal stromal sarcomas (GISTs) are the most common mesenchymal tumours originating in the digestive tract. They have a characteristic morphology, are generally positive for CD117 (c-kit) and are primarily caused by activating mutations in the KIT or PDGFRA genes(1). On rare occasions, they occur in extravisceral locations such as the omentum, mesentery, pelvis and retroperitoneum.GISTs have become a model of multidisciplinary work in oncology: the participation of several specialties (oncologists, pathologists, surgeons, molecular biologists, radiologists…) has forested advances in the understanding of this tumour and the consolidation of a targeted therapy, imatinib, as the first effective molecular treatment in solid tumours. Following its introduction, median survival of patients with advanced or metastatic GIST increased from 18 to more than 60 months. Sunitinib and Regorafenib are two targeted agents with worldwide approval for second- and third-line treatment, respectively, in metastatic GIST.     

胃肠道间质瘤合并消化道癌20例临床病理分析

目的 探讨20例胃肠道间质瘤(gastrointestinal stromal tumor,GIST)合并消化道癌的临床病理特征.方法 回顾性研究165例GIST,对其中20例合并发生消化道癌的病例进行临床病理特征分析并行免疫组化CD117、DOG1等染色.结果 GIST合并发生消化道癌的病例占所有收集GIST病例的12.1%.20例患者中16例男性、4例女性(P＜0.05),年龄44～79岁,平均64.3岁(P＜0.05).19例GIST发生于胃(95.0%),1例发生于食管(5.0%),其中3例为消化道癌根治术中探查发现,其余均为术后病检偶然发现,直径0.4～4.5 cm,平均1.0 cm(P＜0.01).肿瘤细胞均为梭形细胞型,生物学危险度分级为极低危险度18例(90.0%)和低危险度2例(10.0%),免疫标记肿瘤细胞CD117阳性16例(80.0%),DOG1阳性19例(95.0%),其中DOG1阳性、CD117阴性4例(20.0%),CD117阳性、DOG1阴性1例(5.0%).合并发生的消化道癌中胃腺癌10例(50.0%),食管鳞癌9例(45.0%),1例为直肠腺癌(5.0%),肿瘤TNM分期0期1例(5.0%),Ⅰ期3例(15.0%),Ⅱ期7例(35.0%),Ⅲ期9例(45.0%).结论 GIST合并消化道癌并不少见.本病好发于老年男性,其中GIST多发生于胃且生物学危险度低,合并的消化道癌多为胃癌和食管癌.组织学主要为梭形细胞型,危险度分级较低.临床和病理均应重视本病的诊断,特别是在术中探查及术后随访过程中应注意与消化道癌的转移性癌结节鉴别.DOG1能帮助鉴别诊断其他胃肠道间叶源性肿瘤.