查看狗狗原发性心脏血管肉瘤的流行病学、临床和病理特征：51例的回顾的源代码

== 材料与方法 (MATERIALS AND METHODS) ==

===  动物 (Animals) ===

在 2002 年至 2011 年期间，有 55 只原发性心脏 HSA 被临床诊断为原发性心脏 HSA 的狗狗被送往东京农业技术大学兽医临床肿瘤学系进行尸检。其中四只在诊断时未经治疗就被安乐死的狗被排除在外，剩下 51 只狗作为研究材料（表 1）。每只狗的医疗数据包括信号、主诉、体格检查结果、各种诊断测试的结果和治疗方法。所有 51 只狗都死于与 PE 或心脏 HSA 转移有关的原因。常见的主诉包括嗜睡（35 只狗）、虚弱（29 只）、运动不耐受（28 只）、厌食症（22 只）、呼吸困难和咳嗽（18 只）、虚脱（15 只）和体重减轻（12 只）。体格检查的常见异常包括心音低沉（36 只狗）、粘膜苍白（27 只）、心动过速（24 只）、股动脉搏动减弱（17 只）、呼吸用力增加（14 只）、颈静脉扩张（11 只）和腹胀（6 只）。所有 51 例病例在初次就诊时均进行全血细胞计数和血清生化分析。19 只狗的 CBC 结果正常；其余 32 只狗患有轻度贫血 （21）、轻度白细胞增多 （15） 或两者兼而有之 （4）。血清生化参数一般在正常范围内，但血尿素氮浓度（18）和血清谷氨酸丙酮酸转氨酶活性（11）轻度升高。

During the period 2002 to 2011, 55 dogs in which primary cardiac HSA had been diagnosed clinically were submitted to the Department of Veterinary Clinical Oncology, Tokyo University of Agriculture and Technology, for postmortem examination. Four of the dogs, which had been euthanatized without treatment at the time of diagnosis, were excluded, leaving 51 dogs as the study materials (Table 1). The medical data obtained for each dog included signalment, presenting complaints, findings of physical examination, results of various diagnostic tests and method of treatment. All 51 dogs died of causes related to PE or metastasis from cardiac HSA. Common presenting complaints included lethargy (35 dogs), weakness (29), exercise intolerance (28), anorexia (22), dyspnea and cough (18), collapse (15) and weight loss (12). Common abnormalities on physical examination included muffled heart sounds (36 dogs), pale mucous membranes (27), tachycardia (24), weak femoral pulses (17), increased respiratory effort (14), jugular distention (11) and abdominal distention (6). CBCs and serum biochemical analyses were performed at initial presentation in all 51 cases. Results of CBCs were normal for 19 dogs; the remaining 32 dogs had mild anemia (21), mild leukocytosis (15) or both (4). Serum biochemistry parameters were generally within the normal ranges, although mild increases in the blood urea nitrogen concentration (18) and serum glutamic pyruvic transaminase activity (11) were noted.

[[文件:Cardiac.HSA.Table1.png]]

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=== 超声心动图 (Echocardiography) ===

使用 Aloka Prosound SSD-4000、SSD-5500 或 α7 超声机和 3.8 至 7.5 MHz 扇形阵列换能器（Hitachi-Aloka Medical， Ltd.，日本东京）对所有 51 只狗进行超声心动图检查。获得了多个超声心动图视图，以彻底评估狗的心脏肿块，包括左右胸骨旁短轴和长轴视图。所有超声心动图检查均由一名操作员进行，狗侧卧。如果在初次就诊时发现肿块，则超声心动图被认为是阳性的。

Echocardiography was performed in all 51 dogs using an Aloka Prosound SSD-4000, SSD-5500 or α7 ultrasound machine with a 3.8- to 7.5-MHz sector array transducer (Hitachi-Aloka Medical, Ltd., Tokyo, Japan). Multiple echocardiographic views were obtained to thoroughly evaluate dogs for cardiac masses, including right and left parasternal short-axis and long-axis views. All echocardiographic examinations were performed by a single operator with the dogs in lateral recumbency. Echocardiograms were considered to be positive, if a mass was identified at initial presentation.

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=== 治疗和生存时间 (Treatment and survival time) ===

对于所有51只狗，使用Aronsohn [1]和Russell等人[25]的改良TNM世界卫生组织（WHO）分期方案进行临床分期。该系统基于肿瘤大小、浸润程度、淋巴结受累和远处转移体征，适用于犬HSA[14]。根据初次就诊时胸部X线摄影和腹部超声检查显示是否存在转移性疾病，31只没有远处转移证据的狗被归类为2期HAS，20只被归类为3期HSA（表1）。诊断时没有患有 1 期 HSA 的狗。

For all 51 dogs, clinical staging was performed using the modified TNM World Health Organization (WHO) staging protocol of Aronsohn [1] and Russell et al. [25]. This system is based on tumor size, degree of invasion, lymph node involvement and signs of distant metastasis and is applicable to canine HSA [14]. On the basis of the presence or absence of metastatic disease demonstrated by thoracic radiography and abdominal ultrasonography at initial presentation, 31 dogs that did not have evidence of distant metastasis were classified as having stage-2 HAS, and 20 were classified as having stage-3 HSA (Table 1). There were no dogs with stage-1 HSA at the time of diagnosis.


根据治疗方法，将 51 只狗分配到 4 组中的 1 组（表1）：

* A 组 - 不治疗（8 只：第 2、2 阶段;第 3、6 阶段）
* B 组 - 药物治疗（26：第2、12阶段;第3、14阶段）
* C 组 - 心包切除术和肿瘤切除术（12：2、12 期）
* D 组 - 心包切除术、肿瘤切除术和化疗（5：2、5期）


对 B 组的 26 只狗进行了医疗治疗，治疗方案包括给予各种抗生素，糖皮质激素，利尿剂，洋地黄和抗心律失常药物。26 只狗中有 9 只也接受了间歇性心包穿刺术，2 只狗 3 次，4 只狗 2 次，3 只狗 1 次。

C 组所有 12 只狗均接受了心包次全切除术和 RAu 或 RA 肿块的手术切除术（图 1）。

D组的五只狗均接受了心包次全切除术、RAu 或 RA 肿块手术切除术和辅助化疗。

对于 C 组和 D 组，对 10 只狗进行了右侧开胸术，对 7 只狗进行了正中胸骨切开术。


The 51 dogs were allotted to 1 of 4 groups based on methods of treatment: no treatment − group A (8: stage 2, 2; stage 3, 6); medical treatment − group B (26: stage 2, 12; stage 3, 14); pericardectomy and tumor resection − group C (12: stage 2, 12); and pericardectomy, tumor resection and chemotherapy − group D (5: stage 2, 5) (Table 1). Medical management was attempted in 26 dogs of group B. Treatment regimens included administration of various antibiotics, glucocorticoids, diuretics, digitalis and antiarrhythmic drugs. Nine of the 26 dogs were also treated with intermittent pericardiocentesis, 3 times in 2 dogs, twice in 4 and once in 3. All 12 dogs in group C underwent subtotal pericardectomy and surgical resection of the RAu or RA mass (Fig. 1). Five dogs in group D all underwent subtotal pericardectomy, surgical resection of the RAu or RA mass and adjuvant chemotherapy. For groups C and D, a right lateral thoracotomy was performed in 10 dogs, and a median sternotomy was performed in 7.

[[文件:Cardiac.HSA.Fig1.png | 900px]]


选择的化疗策略为3周周期，第1日使用阿霉素（30mg/m^2，IV）和环磷酰胺（100mg/m^2，IV），第 8 天和第 15 天使用长春新碱（0.5mg/m2，IV）[7]。'''该方案在拆线时启动'''，每 21 天重复一次，最多 5 个周期或直到疾病进展。'''每周进行一次体格检查、全血细胞计数和血清生化分析，以发现不良反应'''。

生存时间定义为从临床诊断之日到死亡的时间。

The chemotherapy strategy chosen was 3-week cycles consisting of doxorubicin (30 mg/m^2, IV) and cyclophosphamide (100 mg/m^2, IV) on day 1 and vincristine (0.5 mg/m2, IV) on days 8 and 15 [7]. The protocol was initiated at the time of suture removal and repeated every 21 days for a maximum of 5 cycles or until disease progression. A physical examination and a CBC and serum biochemical analysis were performed weekly to detect adverse reactions.

Survival time was defined as the time from the date of clinical diagnosis to death.

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=== 尸检、组织病理学和免疫组化 (Necropsy, histopathology and immunohistochemistry) ===

对所有 51 只狗进行了完全尸检（单独尸检 34 例;肿瘤切除和尸检 17 例）。在尸检时，对切除的心脏进行大体检查，并确定任何肿瘤的确切位置。然后将其置于 10% 磷酸盐缓冲福尔马林中至少 5 天。固定后，在未进行肿瘤切除的34只狗中，将占位性病灶整体切除并称重，计算肿瘤重量与体重比（TW/BW）（即肿瘤重量（g/体重kg）。对于其余 17 只接受肿瘤切除的狗，当时已经对切除的肿块进行了称重。在每种情况下，从心脏肿块中取出至少 5 个组织块并通过常规方法处理。切片（5μm）用苏木精和伊红（HE）染色，用于光学显微镜检查。此外，还收集了所有内脏器官的组织样本，重点关注那些有肿瘤病变提示转移的器官。对于免疫组织化学研究，使用针对细胞蛋白波形蛋白（1：200，单克隆，克隆MNF 16; Dako，Glostrup，丹麦），细胞角蛋白（1：100，单克隆，克隆Vim 3B4; Dako）、CD31（1：40，单克隆，克隆JC70A; Dako）和血管性血友病因子（因子VIII相关抗原）（1：50，单克隆，克隆F8/86;  Dako）。

Necropsy, histopathology and immunohistochemistry: Complete necropsy was performed on all 51 dogs (necropsy alone 34; tumor resection and necropsy 17). At necropsy, the removed heart was subjected to gross examination, and the exact location of any tumors was identified. It was then placed in 10% phosphate-buffered formalin for at least 5 days. After fixation, in the 34 dogs that had not undergone tumor resection, mass lesions were excised en bloc and weighed, and the tumor weight-to-body weight ratio (TW/BW) was calculated (i.e. tumor weight in g/body weight in kg). For the remaining 17 dogs that had undergone tumor resection, the resected masses had been weighed at that time. In each case, at least 5 tissue blocks were taken from the cardiac mass and processed by routine methods. Sections (5 µm) were stained with hematoxylin and eosin (HE) for light microscopy. In addition, tissue samples were collected from all internal organs, focusing on those with tumorous lesions indicative of metastasis. For the immunohistochemical study, sections were stained by the avidin-biotin-peroxidase method (Vectastain, Vector Laboratories, Burlingame, CA, U.S.A.) using antibodies against the cellular proteins vimentin (1:200, monoclonal, clone MNF 16; Dako, Glostrup, Denmark), cytokeratin (1:100, monoclonal, clone Vim 3B4; Dako), CD31 (1:40, monoclonal, clone JC70A; Dako) and von Willebrand factor (factor VIII-related antigen) (1:50, monoclonal, clone F8/86; Dako).

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=== 统计分析 (Statistical analysis) ===

年龄、体重、肿瘤重量和 TW/BW 值表示为平均值±SD。 Fisher 精确检验用于评估肿块累及RAu的狗（RAu 组）和肿块累及RA的狗（RA 组）的肿块超声心动图检出率的差异。生成 Kaplan-Meier曲线，采用 log-rank 检验比较A组、B组和C组和D组的中位生存时间。 Mann-Whitney U 检验用于评估 C 组和 D 组之间 CBC（WBC、RBC和血小板）或血清生化（ALT、AST、ALP、T-Bil、TP、白蛋白、BUN 和肌酐）数据的差异。RAu 和 RA 组。对于所有统计分析，均使用标准软件，P<0.05 的差异被认为是显著的。

The age, the body weight, the tumor weight and the TW/BW value were expressed as mean ± SD. Fisher’s exact test was used to evaluate the difference in the echocardiographic detection rate of the masses between dogs with masses involving the RAu (RAu group) and dogs with masses involving the RA (RA group). Kaplan-Meier curves were generated, and the log-rank test was used to compare median survival times between groups A, B and C, and D. Mann-Whitney U test was used to evaluate the difference in the data for CBCs (WBC, RBC and platelet) or serum biochemistry (ALT, AST, ALP, T-Bil, TP, albumin, BUN and creatinine) between group C and group D. Student’s t test was used to evaluate the difference in the TW/BW value between the RAu and RA groups. For all statistical analyses, standard software was used, and differences of P<0.05 were considered to be significant.

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