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

== 讨论 (Discussion) ==

心脏 HSA 是狗中最常见的原发性心脏肿瘤，最常见于老年 GS 和 GR [1,4,15,19,24,27,30]，通常累及 RA 或 RAu [1,2,13,19,24]。肿瘤是高度恶性的，在病程早期发生广泛的血液学播散[1,19,22]。因此，人们认为心脏HSA的治疗具有挑战性，并且肿瘤预后严重[30]。在本研究中，在尸检时发现 51 只患有原发性心脏 HSA 的狗中有 38 只 （75%） 存在转移性疾病。该图强调了这样一个事实，即这种肿瘤向其他器官的广泛转移是常见的。


这一系列病例的流行病学数据与其他研究一致[1,19,24]。在我们的系列中，受影响的狗的平均年龄为 10.7 岁，没有一只狗小于 5 岁。在早期的文献中，已经认识到患有心脏 HSA 的狗的这种年龄倾向[1,4,19,23,24]。男性和女性的总数分别为 32人和 19 人。雄性/雌性比例为 1.68，表明雄性略占优势，尽管我们无法将这一数字与整个医院人群中雄性狗的比例进行比较。该信息与其他报告男性对犬 HSA 的性别偏好的研究相对应[4, 19, 23]。其他研究表明，没有特别的性别偏好[1,30]，但有研究表明，绝育的女性可能风险增加[32]。


我们的研究样本太小，无法得出关于品种分布的结论，但本系列中有11个遗传资源，这是一个在早期研究中出现的品种[1,2,3,4,26]。同样明显的是，马耳他犬（9/51）和微型腊肠犬（7/51）品种比其他品种更频繁。以前的任何报告都没有提到这两个品种对犬类 HSA 的易感性。据认为，马耳他犬和微型腊肠犬肿瘤的高发率并非归因于这些品种的“日本品系”，但可能反映了这些品种对某些环境因素的易感性。据报道，心脏HSA在GS中最常见[1,2,4,19,24]，但本系列研究未发现这种倾向。这种差异可能反映了当前和以前研究的时间范围、地理和品种流行率的差异。


至于原发性心脏 HSA 的位置，我们发现这些肿瘤最常出现在 RAu 和 RA 中，但偶尔出现在RV，心脏底部和左心房。原发性心脏 HSA 通常位于 RA 或 RAu[1,2,13,19,24]，心脏的其他部位仅偶尔受累[1,11,19]。在本系列研究中，受心脏 HSA 影响的心脏部位与先前报道的部位基本相同[1,19,22]，无论本研究与其他研究之间的品种差异如何。


人类心脏HSA最常见的部位是 RA[5]，狗也是如此[1,2,13,19,24]。与心脏其他部位相比，人类其他类型的肉瘤在 RA 中也更常见[5]。该部位是牛恶性淋巴瘤的常见部位，据报道，未分化结缔组织的病灶（常见于牛 RA 心外膜下）与恶性淋巴瘤的受累部位相对应[16]。这种胚胎结缔组织也存在于其他动物的 RA 中[16]，它似乎有可能引起各种类型的肉瘤，包括 HSA [19]。有趣的是，本系列中的大多数 RA 肿块作为孤立肿块起源于 RA 的前外侧区域;最小和最离散的肿瘤主要位于心外膜下方，就在房室交界处上方。

Cardiac HSA is the most commonly reported primary neoplasm of the heart in dogs, occurring most frequently in older GSs and GRs [1, 4, 15, 19, 24, 27, 30] and usually involving the RA or RAu [1, 2, 13, 19, 24]. The tumor is highly malignant, and widespread hematological dissemination occurs early in the course of the disease [1, 19, 22]. Therefore, it has been considered that treatment for cardiac HSA is challenging and that the tumor has a grave prognosis [30]. In the present study, metastatic disease was found in 38 of 51 (75%) dogs with primary cardiac HSA at necropsy. This figure emphasizes the fact that widespread metastasis of this tumor to other organs is common.

The epidemiologic data in this series of cases were consistent with those of other studies [1, 19, 24]. The mean age of affected dogs in our series was 10.7 years, and none of the dogs was younger than 5 years of age. This age disposition for dogs with cardiac HSA has been recognized throughout the earlier literature [1, 4, 19, 23, 24]. The total numbers of males and females were 32 and 19, respectively. The male/female ratio was 1.68, indicating a slight predominance in males, although we were unable to compare this figure with the proportions of male dogs in hospital populations at large. This information corresponds to other studies that have reported a male sex predilection for canine HSA. [4, 19, 23]. Other studies have indicated no particular sex predilection [1, 30], although it has been suggested that spayed females may be at increased risk [32].

Our study sample was too small to allow conclusions to be drawn about breed distribution, but there were 11 GRs in the present series, and this was a breed that had featured in earlier investigations [1, 2, 3, 4, 26]. It was also evident that Maltese (9/51) and Miniature Dachshund (7/51) breeds were represented more frequently than others. Predisposition of these 2 breeds to canine HSA has not been mentioned by any previous reports. It is considered that the high frequency of the tumor in Maltese and Miniature Dachshunds is not attributable to ‘Japan strains’ of these breeds, but possibly reflects a predisposition of these breeds to certain environmental factors. Although cardiac HSA is reportedly most common in GSs as mentioned above [1, 2, 4, 19, 24], such a predilection was not noted in the present series. Such variations may reflect differences in the time frame, geography and breed prevalence of the present and previous studies.

As to the location of primary cardiac HSA, we found that these tumors arose most often in the RAu and RA, but occasionally in the RV, heart base and left atrium. Primary cardiac HSAs are usually located in the RA or RAu [1, 2, 13, 19, 24], and other sites of the heart are affected only occasionally [1, 11, 19]. In the present series, the sites in the heart affected by cardiac HSAs were primarily the same as those reported previously [1, 19, 22], regardless of breed differences between this and other studies.

The most frequent location of cardiac HSAs in humans is the RA [5], as is the case in dogs [1, 2, 13, 19, 24]. Other types of sarcomas in humans also occur more commonly in the RA than in other parts of the heart [5]. This site is a frequent location for malignant lymphoma in cattle, and it has been reported that foci of undifferentiated connective tissue, often found in the subepicardium of the RA of cattle, correspond to sites of involvement of malignant lymphoma [16]. This embryonic connective tissue is also found in the RA of other animals [16], and it seems possible that it could give rise to various types of sarcomas including HSAs [19]. Interestingly, the majority of RA masses in the present series originated from the anterolateral regions of the RA as solitary masses; the smallest and most discrete tumors were located predominantly beneath the epicardium just above the atrioventricular junction.


准确诊断心脏肿块并确定其位置可以产生对治疗计划很重要的信息。在本系列研究中，在 51 只患有原发性心脏 HSA 的狗中，有 38 只 （75%） 通过超声心动图检测到提示心脏肿块的病变。二维超声心动图检测占位性病变的灵敏度显著低于 RAu 肿块。RA 组的平均 TW/BW 值显著高于 RAu 组，提示超声心动图检测可能与肿瘤大小有关[12]。此外，肿瘤位置似乎是一个重要因素，因为现有数据表明，位于 RAu 中的 HSA 被超声心动图检测到的可能性显着降低。普通超声成像技术通常无法在正常犬中观察到 RAu，这表明该区域相对较小的肿瘤可能难以检测到[12]。无论如何，本研究中确定的超声心动图的敏感性表明，该技术在检测心脏肿块方面比以前认为的更有效[2,9,12,17,22]。技术进步带来了更好的灰度分辨率，使用更新的仪器可以提高质量检测的灵敏度[12]。


关于原发性心脏 HSA 的治疗，许多狗主人可能会选择仅使用心包穿刺术进行姑息治疗，因为许多受影响的狗在诊断时有转移的证据[6,30]。心包穿刺术可预测与显著的临床改善相关，但心包填塞的临床体征通常会在数日内复发，常导致死亡或提示安乐死[30]。如果早期发现肿瘤肿块，但无远处转移的明显证据，有时可以通过手术切除肿瘤肿块，特别是当它局限于 RAu 时[10]。有报道称，切除 RA 肿块用于治疗心脏 HSA；然而，与单纯心包切除术或不进行手术治疗的随访相比，该应用并未显示可提高生存率[1,4,28,33]。Dunning 等[9]报道，心包切除术和肿块切除术后心脏 HSA 患者的中位生存时间为 16 天。相比之下，最近对 23 只接受正中胸骨切开术或侧开胸术进行心包切除术和肿块切除术的狗的研究揭示了有希望的结果；15 例未接受辅助化疗的狗的平均生存期和中位生存期分别为 46 日和 42 日[33]。在本研究中，与不治疗（A 组）或单独药物治疗（B 组）相比，心包切除术和肿瘤手术切除术（C 组）的组合与显着更长的生存时间相关。因此，我们有限的经验表明，开胸手术和手术治疗有可能提高患有心脏 HSA 的狗的生存时间。然而，可能很难轻易地评估和比较手术治疗的效果与先前研究中报告的效果，因为我们的 C 组不包括患有 3 期肿瘤的狗。


在HSA患者的各种临床研究中，已经评估了辅助化疗，并显示出延长原发性 HSA 病变手术切除后寿命的希望[8,18,21,31]。据报道，基于多柔比星的方案对患有 HSA 的狗有中等疗效，而不包括多柔比星的方案疗效有限或没有疗效[30]。一项研究纳入了 23 例原发性心脏 HSA 的狗，发现 8 只在肿块切除后接受化疗的狗的平均生存时间为 164 日，而未接受化疗的 15 只狗的平均生存时间为 46天[33]。因此，与单独手术相比，一些术后辅助化疗方案似乎有可能延长生存期。在本研究中，51 只狗中有 5 只在心包切除术和肿瘤切除术后接受了辅助化疗。这些狗的存活时间明显长于手术后未接受化疗的 12 只狗。本研究中上述5只狗的平均生存时间为 183 天，与Weisse等[33]报道的生存时间相符。

所有 5 只狗使用的化疗方案包括多柔比星、环磷酰胺和长春新碱。选择这种疗法的最重要原因是其在人软组织肉瘤治疗试验中的已知疗效[25]。尽管该系列中只有少数狗接受了阿霉素、环磷酰胺和长春新碱的辅助化疗，但我们得出结论，手术后的这种化疗可能对患有原发性心脏 HSA 的狗有效。

Accurate diagnosis of a cardiac mass and defining its location can yield information that is important for therapeutic planning. In the present series, a lesion suggestive of a cardiac mass was detected echocardiographically in 38 (75%) of the 51 dogs with primary cardiac HSAs. The sensitivity of two-dimensional echocardiography for detection of a mass lesion was significantly lower for RAu than for RA masses. The mean TW/BW value in the RA group was significantly higher than that in the RAu group, indicating that echocardiographic detection may be related to tumor size [12]. In addition, tumor location appears to be an important factor, because the available data indicate that HSAs located in the RAu are significantly less likely to be detected by echocardiography. The RAu is usually not visualized in normal dogs by ordinary ultrasound imaging techniques, suggesting that relatively small tumors in this area may be difficult to detect [12]. In any event, the sensitivity of echocardiography determined in this study suggests that this technique is much more effective for detection of cardiac masses than has been considered previously [2, 9, 12, 17, 22]. Technological advances have led to better greyscale resolution, and an improvement of sensitivity for detection of masses may be possible with newer instrumentation [12].

With regard to the treatment of primary cardiac HSA, many dog owners may elect palliation with pericardiocentesis alone, because many affected dogs have evidence of metastasis at the time of diagnosis [6, 30]. Pericardiocentesis is predictably associated with marked clinical improvement, but clinical signs of cardiac tamponade typically recur within a few days, often resulting in death or prompting euthanasia [30]. If identified early without gross evidence of distant metastasis, a tumor mass can sometimes be removed surgically, particularly if it is localized to the RAu [10]. Resection of an RA mass has been reported for treatment of cardiac HSA; however, it has not been shown to improve survival in comparison with either pericardectomy alone or follow-up without surgical treatment [1, 4, 28, 33]. Dunning et al. [9] reported a median survival time of 16 days in dogs with cardiac HSA following pericardectomy and mass resection. In contrast, a recent study of 23 dogs that underwent median sternotomy or lateral thoracotomy for pericardectomy and mass resection revealed promising results; the mean and median survival times of the 15 dogs treated in this way without adjuvant chemotherapy, were 46 and 42 days, respectively [33]. In the present study, a combination of pericardectomy and surgical resection of the tumor (group C) was associated with significantly longer survival time, compared with no treatment (group A) or medical management alone (group B). Thus, our limited experience suggests that thoracotomy and surgical treatment have the potential to improve the survival time of dogs with cardiac HSA. However, it might be difficult to readily evaluate and compare the effects of surgical treatment with those reported in previous studies, because our group C included no dogs with stage-3 tumors.

Chemotherapy in an adjuvant setting has been evaluated in various clinical studies of dogs with HSA and has shown promise for prolonging life after surgical resection of the primary HSA lesion [8, 18, 21, 31]. Doxorubicin-based protocols reportedly have moderate efficacy for dogs with HSA, whereas protocols that do not include doxorubicin have had limited or no efficacy [30]. In a study of 23 dogs with primary cardiac HSA, the mean survival time for 8 dogs that received chemotherapy after resection of the mass was 164 days, compared with 46 days for 15 dogs that did not receive such chemotherapy [33]. Therefore, it appears that some postoperative adjuvant chemotherapy protocols have the potential to prolong survival in comparison with surgery alone. In the present study, 5 of the 51 dogs received adjuvant chemotherapy after pericardectomy and tumor resection. Those dogs showed significantly longer survival than the 12 dogs that did not receive chemotherapy after surgery. The mean survival time of 183 days for the above 5 dogs in this study is compatible with that reported by Weisse et al. [33].

The chemotherapy protocol used in all 5 dogs included doxorubicin, cyclophosphamide and vincristine. The most important reason for this choice was its known efficacy in therapeutic trials with human soft tissue sarcoma [25]. Although only a small number of dogs in this series underwent adjuvant chemotherapy with doxorubicin, cyclophosphamide and vincristine, we conclude that such chemotherapy after surgery may be effective for dogs with primary cardiac HSA.



总之，在本系列报告的 51 只患有心脏 HSA 的狗中，马耳他犬和微型腊肠犬品种以及 GR 比其他品种更常见。如前所述，在大多数情况下，肿瘤局限于 RAu 和 RA。与RAu中的肿块相比，RAu中肿块的超声心动图检出率较低，这可能与肿瘤大小和/或位置有关。接受辅助化疗的心脏 HSA 狗的生存时间明显更长，这表明术后化疗在这种情况下可能有用。

In conclusion, among 51 dogs with cardiac HSA reported in this series, the Maltese and Miniature Dachshund breeds, as well as the GR, were represented more frequently than other breeds. In most cases, the tumor was localized to the RAu and RA, as reported previously. The lower echocardiographic detection rate of masses located in the RAu compared with those in the RA may have been related to tumor size and/or location. The significantly longer survival time for dogs with cardiac HSA receiving adjuvant chemotherapy indicates that postoperative chemotherapy would probably be useful in this setting.

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