犬内脏血管肉瘤单独手术治疗或手术加多柔比星治疗：37例（2005-2014年） - 版本历史

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	* [https://todaysveterinarypractice.com/nutrition/nutritional-management-of-veterinary-patients-with-neoplasia/ Nutritional Management of Patients with Neoplasia] [[小动物肿瘤患者的营养管理]]		* [https://todaysveterinarypractice.com/nutrition/nutritional-management-of-veterinary-patients-with-neoplasia/ Nutritional Management of Patients with Neoplasia] [[小动物肿瘤患者的营养管理]]
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		+	* [[狗狗心包积液]]

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 * [27] [https://pubmed.ncbi.nlm.nih.gov/9815908 Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: A randomized multi-institutional clinical trial. Clin Cancer Res. 1995]
 * [28] Thamm DH. Miscellaneous tumors: hemangiosarcoma. In: Withrow SJ, Vail DM, Page RL, editors. Withrow and MacEwen’s Small Animal Clinical Oncology. 5th ed. St. Louis, Missouri: Elsevier Saunders; 2013
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		+	* [27] [https://pubmed.ncbi.nlm.nih.gov/9815908 Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: A randomized multi-institutional clinical trial. Clin Cancer Res. 1995]
	* [28] Thamm DH. Miscellaneous tumors: hemangiosarcoma. In: Withrow SJ, Vail DM, Page RL, editors. Withrow and MacEwen’s Small Animal Clinical Oncology. 5th ed. St. Louis, Missouri: Elsevier Saunders; 2013		* [28] Thamm DH. Miscellaneous tumors: hemangiosarcoma. In: Withrow SJ, Vail DM, Page RL, editors. Withrow and MacEwen’s Small Animal Clinical Oncology. 5th ed. St. Louis, Missouri: Elsevier Saunders; 2013

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−	虽然很难将我们的研究人群与先前发表的被诊断患有内脏HSA的狗的研究进行直接比较，但我们的结果与先前报道的单独接受手术治疗和手术后全身治疗的狗的生存时间相似。根据大多数研究，基于多柔比星的辅助方案将脾脏 HSA 狗的存活时间从平均 3 个月提高到 9 个月（1,3,16,25,33,34）。在这项研究中，患有内脏 HSA 的狗的总体 MST 为 179 天（~6 个月），1 年生存率为 29.2%~~。单独接受手术治疗的狗的~~ MST 为 2 ~~个月，接受手术治疗的狗随后接受多柔比星治疗的狗的~~ MST 为 9 个月。鉴于总体预后不良，需要替代治疗方式来治疗这种疾病。Wendelburg等人（31）报告说，接受基于多柔比星和节拍化疗联合治疗的狗的存活时间主观上比单独接受基于多柔比星或节拍化疗的狗的存活时间长。在另一项研究（17）中，在单独的常规最大耐受剂量化疗的基础上增加节律化疗与更长的进展时间和生存时间相关。根据这些结果，有理由相信，使用节拍疗法可能在减缓 HSA 进展方面发挥作用，这可能是由于其抗血管生成作用和免疫调节（35）。犬 HSA 细胞系和肿瘤样本表达受体酪氨酸激酶干细胞因子受体（KIT）、血小板衍生生长因子受体（PDGFR）和血管内皮生长因子受体 ~~（VEGFR）。Toceranib 是一种多靶点小分子抑制剂，可阻断~~ KIT、PDGFR 和 VEGFR 信号转导（21,36）。Gardner等人（21）在基于多柔比星的化疗后使用托塞拉尼作为犬脾HSA的维持治疗时，未发现无病间隔期或总生存期的改善。有必要研究基于托塞拉尼布和多柔比星的方案的同时给药而不是顺序给药，以确定这种组合是否对生存时间有显著影响（21）。除了节拍器或靶向治疗与最大耐受剂量化疗的组合外，免疫疗法也在临床试验中进行了评估 ~~（27）。例如，在脾切除术后，用免疫调节剂脂质体封装的胞壁酰三肽磷脂酰乙醇胺（L~~-MTP-~~PE）联合多柔比星和环磷酰胺治疗的狗比接受手术和最大耐受剂量化疗的狗有更好的结果（27）。需要进一步的研究来确认在诊断患有内脏~~ HSA 的狗使用基于多柔比星的化疗方案后使用节律化疗、免疫疗法或靶向疗法作为维持疗法的潜在益处。	+	虽然很难将我们的研究对象与先前发表的被诊断患有内脏 HSA 的狗的研究进行直接比较，但我们的结果与先前报道的单独接受手术治疗和手术后全身治疗的狗的生存时间相似。根据大多数研究，'''基于多柔比星的辅助方案将脾脏 HSA 狗的存活时间从平均 3 个月提高到 9 个月''' （1,3,16,25,33,34）。在这项研究中，患有内脏 HSA 的狗的总体 MST 为 179 天（~6 个月），1 年生存率为 29.2%。'''单独接受手术治疗的狗的 MST 为 2 个月'''，接受手术治疗的狗随后接受多柔比星治疗的狗的 MST 为 9 个月。鉴于总体预后不良，需要替代治疗方式来治疗这种疾病。Wendelburg等人（31）报告说，接受基于多柔比星和节拍化疗联合治疗的狗的存活时间主观上比单独接受基于多柔比星或节拍化疗的狗的存活时间长。在另一项研究（17）中，在单独的常规最大耐受剂量化疗的基础上增加节律化疗与更长的进展时间和生存时间相关。根据这些结果，有理由相信，使用节拍疗法可能在减缓 HSA 进展方面发挥作用，这可能是由于其抗血管生成作用和免疫调节（35）。犬 HSA 细胞系和肿瘤样本表达受体酪氨酸激酶干细胞因子受体（KIT）、血小板衍生生长因子受体（PDGFR）和血管内皮生长因子受体（VEGFR）。'''Toceranib 是一种多靶点小分子抑制剂'''，可阻断 KIT、PDGFR 和 VEGFR 信号转导（21,36）。Gardner等人（21）在基于多柔比星的化疗后使用'''托塞拉尼'''作为犬脾 HSA 的维持治疗时，未发现无病间隔期或总生存期的改善。有必要研究基于托塞拉尼布和多柔比星的方案的同时给药而不是顺序给药，以确定这种组合是否对生存时间有显著影响（21）。除了节拍器或靶向治疗与最大耐受剂量化疗的组合外，免疫疗法也在临床试验中进行了评估（27）。例如，在脾切除术后，'''用免疫调节剂脂质体封装的胞壁酰三肽磷脂酰乙醇胺（L-MTP-PE）联合多柔比星和环磷酰胺治疗的狗比接受手术和最大耐受剂量化疗的狗有更好的结果'''（27）。需要进一步的研究来确认在诊断患有内脏 HSA 的狗使用基于多柔比星的化疗方案后使用节律化疗、免疫疗法或靶向疗法作为维持疗法的潜在益处。

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	Scientific data suggest that the biological behavior of HSA may vary according to the tissue of origin (4,5,10,24–26). Dogs with dermal HSA may experience prolonged survival or be cured after surgical excision compared with dogs with HSA in other anatomic locations (10). On the contrary, dogs with visceral HSA usually die within a year despite adequate local and systemic treatments (1,13–16). When compared to HSA located in the spleen, right atrium, and liver, primary renal HSA has been associated with a less aggressive disease while retroperitoneal HSA has been associated with a poor clinical outcome due to the high percentage of dogs presenting with metastases at the time of diagnosis (25,26). In contrast to previous studies, our study did not find that primary tumor location influenced prognosis. One possible explanation for this lack of correlation between primary tumor location and survival time is the heterogenous population of dogs in our study. The most common primary organ affected was the spleen, accounting for 81.1% (30/37) of cases. Other primary sites affected were underrepresented, including liver (2/37, 5.4%), kidneys (2/37, 5.4%), intestines (1/37, 2.7%), urinary bladder (1/37, 2.7%), and lymph node (1/37, 2.7%). The absence of significant difference in outcome among dogs diagnosed with HSA located at different primary sites may represent a false-negative result due to a type II error related to the small sample size of the study (32). Therefore, it is not possible to establish definitive conclusions on the importance of primary tumor location of HSA based on our study.		Scientific data suggest that the biological behavior of HSA may vary according to the tissue of origin (4,5,10,24–26). Dogs with dermal HSA may experience prolonged survival or be cured after surgical excision compared with dogs with HSA in other anatomic locations (10). On the contrary, dogs with visceral HSA usually die within a year despite adequate local and systemic treatments (1,13–16). When compared to HSA located in the spleen, right atrium, and liver, primary renal HSA has been associated with a less aggressive disease while retroperitoneal HSA has been associated with a poor clinical outcome due to the high percentage of dogs presenting with metastases at the time of diagnosis (25,26). In contrast to previous studies, our study did not find that primary tumor location influenced prognosis. One possible explanation for this lack of correlation between primary tumor location and survival time is the heterogenous population of dogs in our study. The most common primary organ affected was the spleen, accounting for 81.1% (30/37) of cases. Other primary sites affected were underrepresented, including liver (2/37, 5.4%), kidneys (2/37, 5.4%), intestines (1/37, 2.7%), urinary bladder (1/37, 2.7%), and lymph node (1/37, 2.7%). The absence of significant difference in outcome among dogs diagnosed with HSA located at different primary sites may represent a false-negative result due to a type II error related to the small sample size of the study (32). Therefore, it is not possible to establish definitive conclusions on the importance of primary tumor location of HSA based on our study.
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		+	虽然很难将我们的研究人群与先前发表的被诊断患有内脏HSA的狗的研究进行直接比较，但我们的结果与先前报道的单独接受手术治疗和手术后全身治疗的狗的生存时间相似。根据大多数研究，基于多柔比星的辅助方案将脾脏 HSA 狗的存活时间从平均 3 个月提高到 9 个月（1,3,16,25,33,34）。在这项研究中，患有内脏 HSA 的狗的总体 MST 为 179 天（~6 个月），1 年生存率为 29.2%。单独接受手术治疗的狗的 MST 为 2 个月，接受手术治疗的狗随后接受多柔比星治疗的狗的 MST 为 9 个月。鉴于总体预后不良，需要替代治疗方式来治疗这种疾病。Wendelburg等人（31）报告说，接受基于多柔比星和节拍化疗联合治疗的狗的存活时间主观上比单独接受基于多柔比星或节拍化疗的狗的存活时间长。在另一项研究（17）中，在单独的常规最大耐受剂量化疗的基础上增加节律化疗与更长的进展时间和生存时间相关。根据这些结果，有理由相信，使用节拍疗法可能在减缓 HSA 进展方面发挥作用，这可能是由于其抗血管生成作用和免疫调节（35）。犬 HSA 细胞系和肿瘤样本表达受体酪氨酸激酶干细胞因子受体（KIT）、血小板衍生生长因子受体（PDGFR）和血管内皮生长因子受体（VEGFR）。Toceranib 是一种多靶点小分子抑制剂，可阻断 KIT、PDGFR 和 VEGFR 信号转导（21,36）。Gardner等人（21）在基于多柔比星的化疗后使用托塞拉尼作为犬脾HSA的维持治疗时，未发现无病间隔期或总生存期的改善。有必要研究基于托塞拉尼布和多柔比星的方案的同时给药而不是顺序给药，以确定这种组合是否对生存时间有显著影响（21）。除了节拍器或靶向治疗与最大耐受剂量化疗的组合外，免疫疗法也在临床试验中进行了评估（27）。例如，在脾切除术后，用免疫调节剂脂质体封装的胞壁酰三肽磷脂酰乙醇胺（L-MTP-PE）联合多柔比星和环磷酰胺治疗的狗比接受手术和最大耐受剂量化疗的狗有更好的结果（27）。需要进一步的研究来确认在诊断患有内脏 HSA 的狗使用基于多柔比星的化疗方案后使用节律化疗、免疫疗法或靶向疗法作为维持疗法的潜在益处。
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		+	我们的报告存在回顾性研究固有的局限性、狗的异质性种群和少量患者。被诊断患有HSA的狗位于脾脏以外的主要部位，代表性不足。此外，几名患者接受了不同的治疗，这些治疗是根据临床医生的判断确定的。术后辅助化疗患者治疗或不治疗的决定在病历中并不明确。由于对预后不良、不依从性、经济拮据或难以治疗不合作的动物的误解，主人的偏见可能会影响患者的治疗决策和结果。最后，没有一只狗进行尸检以确认死因，并假设它们死于HSA。
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		+	总之，本手稿中报告的数据表明，使用当前标准护理方法（例如积极手术和化疗）或单独手术治疗的内脏 HSA 狗的总生存率仍然很差，大多数狗在一年内死于疾病。临床分期与预后相关，被诊断患有 I 期肿瘤的狗比患有更晚期 HSA 的狗有更好的结果。在这项回顾性研究中，术后加用单药阿霉素显示出生存获益，尽管效果不大。因此，应评估新的治疗方法，包括使用维持性节律化疗、免疫治疗或最大耐受剂量化疗后的靶向治疗。对犬 HSA 生物学的进一步研究可能会提高对这种疾病的理解，并有助于推进治疗。CVJ
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		+	Although it is difficult to make direct comparisons between our study population and previously published studies of dogs diagnosed with visceral HSA, our results were similar to previously reported survival times of dogs treated with surgery alone and surgery followed by systemic therapy. According to the majority of studies, adjuvant doxorubicin-based protocols improve survival times of dogs with splenic HSA from an average of 3 to 9 mo (1,3,16,25,33,34). The overall MST of dogs with visceral HSA in this study was 179 d (~6 mo), with a 1-year survival rate of 29.2%. The MST of dogs treated with surgery alone was 2 mo and the MST of dogs treated with surgery followed by doxorubicin was 9 mo. Given the overall poor prognosis, alternative therapeutic modalities are needed for treatment of this disease. Wendelburg et al (31) reported that survival time of dogs treated with the combination of doxorubicin-based and metronomic chemotherapy was subjectively longer than survival time of dogs receiving either doxorubicin-based or metronomic chemotherapy alone. In another study (17), the addition of metronomic chemotherapy to conventional maximum-tolerated dose chemotherapy alone was associated with a longer time to progression and survival time. According to these results, it is reasonable to believe that the use of metronomic therapy may play a role in slowing the progression of HSA possibly due to its anti-angiogenic effect and immune modulation (35). Canine HSA cell lines and tumor samples express the receptor tyrosine kinases stem cell factor receptor (KIT), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). Toceranib is a multitargeted small molecule inhibitor that blocks signaling of KIT, PDGFR and VEGFR (21,36). No improvement in disease-free interval or overall survival was noted by Gardner et al (21) when toceranib was used as maintenance therapy after doxorubicin-based chemotherapy for canine splenic HSA. The investigation of concurrent rather than sequential administration of toceranib and doxorubicin-based protocols is warranted to determine if this combination has a significant impact on survival time (21). In addition to the combination of metronomic or targeted therapies with maximum-tolerated dose chemotherapy, immunotherapy has also been evaluated in clinical trials (27). For instance, dogs treated with the immunomodulator liposome encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) combined with doxorubicin and cyclophosphamide after splenectomy had a better outcome than dogs treated with surgery and maximum-tolerated dose chemotherapy (27). Further studies are needed to confirm the potential benefit of using metronomic chemotherapy, immunotherapy, or targeted therapies as maintenance therapies after a doxorubicin-based chemotherapy regimen for dogs diagnosed with visceral HSA.
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		+	Our report suffers from limitations that are inherent in retrospective studies, the heterogenous population of dogs and the small number of patients. Dogs diagnosed with HSA located in primary sites other than the spleen were underrepresented. Also, several patients had different therapies that were determined based on the clinician’s discretion. The decision to treat or not to treat patients with adjuvant chemotherapy after surgery was not clear in the medical records. It is possible that owner bias due to misunderstanding of the poor prognosis, non-compliance, financial constraints, or difficulty treating an uncooperative animal could have influenced the treatment decision and outcome for the patients. Lastly, none of the dogs had a necropsy carried out to confirm the cause of death, and it was assumed that they died of HSA.
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		+	In summary, the data reported in this manuscript demonstrate that the overall survival of dogs with visceral HSA treated with either the current standard-of-care-approach, such as aggressive surgery and chemotherapy, or surgery alone, remain poor with most dogs succumbing to their disease within a year. Clinical stage was associated with prognosis and dogs diagnosed with stage I tumors had better outcomes than dogs with more advanced HSA. In this retrospective study, the addition of single agent doxorubicin after surgery showed a survival benefit, albeit modest. Thus, novel treatment approaches, including the use of maintenance metronomic chemotherapy, immunotherapy, or targeted therapies after maximum-tolerated dose chemotherapy, should be evaluated. Additional investigation into the biology of canine HSA will likely improve the understanding of this disease and help with the advancement of therapies. CVJ
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−	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时'''被诊断为转移的狗的生存时间最短'''~~，这可能是由于不适合手术的转移性病变出血，并且经常与这种~~'''疾病相关的凝血异常加剧''' （1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。	+	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时'''被诊断为转移的狗的生存时间最短'''，这可能是由于'''不适合手术的转移性病变出血'''，并且经常与这种'''疾病相关的凝血异常加剧''' （1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。

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−	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时'''被诊断为转移的狗的生存时间最短'''~~，这可能是由于不适合手术的转移性病变出血，并且经常与这种疾病相关的凝血异常加剧~~ （1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。	+	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时'''被诊断为转移的狗的生存时间最短'''，这可能是由于不适合手术的转移性病变出血，并且经常与这种'''疾病相关的凝血异常加剧''' （1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。

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−	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时被诊断为转移的狗的生存时间最短，这可能是由于不适合手术的转移性病变出血，并且经常与这种疾病相关的凝血异常加剧（1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。	+	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时'''被诊断为转移的狗的生存时间最短'''，这可能是由于不适合手术的转移性病变出血，并且经常与这种疾病相关的凝血异常加剧（1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。

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	All 37 dogs were included in the overall survival analysis, with 13 dogs censored. Eleven dogs were censored since they were alive at the time of data analysis and 2 dogs due to being lost to follow-up. The overall MST for dogs diagnosed with visceral HSA was 179 d (range: 1 to > 1747 d) and the 1-year survival rate was estimated to be 29.2% (Figure 3).		All 37 dogs were included in the overall survival analysis, with 13 dogs censored. Eleven dogs were censored since they were alive at the time of data analysis and 2 dogs due to being lost to follow-up. The overall MST for dogs diagnosed with visceral HSA was 179 d (range: 1 to > 1747 d) and the 1-year survival rate was estimated to be 29.2% (Figure 3).

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		+	== 讨论 (Discussion) ==
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		+	犬内脏HSA的治疗在过去20年中没有发生重大变化，这可能是由于对肿瘤生物学的了解不足（21,29）。直到最近，涉及分子发病机制、细胞个体发育、肿瘤微环境和 HSA 异质性的基础研究才成为兽医学的重点领域（21,29）。与之前关于被诊断患有内脏 HSA 的狗的结果和预后因素的回顾性研究相比，我们的研究显示了类似的结果。
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		+	历史上，患有HSA晚期临床阶段的狗的生存时间比患有早期疾病的狗短（1,11,27,28）。与以前的研究一致，我们的研究发现诊断时的临床分期与生存时间相关。正如预期的那样，在初次就诊时被诊断为转移的狗的生存时间最短，这可能是由于不适合手术的转移性病变出血，并且经常与这种疾病相关的凝血异常加剧（1,30）。患有 I 期肿瘤的狗比患有 II 期疾病的狗具有更长的生存时间，这可能是由于缺乏肿瘤出血和肿瘤细胞继发植入腹腔或胸腔（1,10,27,31）。
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		+	科学数据表明，HSA 的生物学行为可能因起源组织而异（4,5,10,24–26）。与在其他解剖位置患有 HSA 的狗相比，患有真皮 HSA 的狗可能会经历更长的生存期或手术切除后治愈（10）。相反，尽管进行了充分的局部和全身治疗，但患有内脏HSA的狗通常会在一年内死亡（1,13-16）。与位于脾脏、右心房和肝脏的 HSA 相比，原发性肾 HSA 与侵袭性较低的疾病相关，而腹膜后 HSA 与较差的临床结果相关，因为在诊断时出现转移的狗比例很高（25,26）。与以前的研究相比，我们的研究没有发现原发性肿瘤位置会影响预后。原发肿瘤位置和生存时间之间缺乏相关性的一种可能解释是我们研究中狗的异质性种群。最常见的原发性器官是脾脏，占病例的81.1%（30/37）。其他受累的原发部位代表性不足，包括肝脏（2/37,5.4%）、肾脏（2/37,5.4%）、肠道（1/37,2.7%）、膀胱（1/37,2.7%）和淋巴结（1/37,2.7%）。由于与研究的小样本量相关的 II 型错误，位于不同主要部位的被诊断患有 HSA 的狗在结果上没有显着差异可能代表假阴性结果（32）。因此，根据我们的研究，不可能就HSA原发肿瘤位置的重要性得出明确的结论。
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		+	Treatment for canine visceral HSA has not changed considerably in the past 20 y, probably due to a poor understanding of the tumor biology (21,29). It is only recently that basic research involving molecular pathogenesis, cellular ontogeny, tumor microenvironment, and heterogeneity of HSA has become an area of emphasis in veterinary medicine (21,29). Our study showed similar results compared to previous retrospective studies regarding outcome and prognostic factors for dogs diagnosed with visceral HSA.
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		+	Dogs with advanced clinical stage of HSA historically have had shorter survival times than dogs with early-stage disease (1,11,27,28). In agreement with previous studies, our study found that clinical stage at diagnosis was associated with survival time. As expected, dogs diagnosed with metastases at initial presentation had the shortest survival time, possibly due to hemorrhage from metastatic lesions that are not amenable to surgery and compounded by coagulation abnormalities that are frequently associated with this disease (1,30). Dogs with stage I tumors had longer survival times than dogs with stage II disease probably due to lack of tumor hemorrhage and secondary implantation of neoplastic cells into the abdominal or thoracic cavities (1,10,27,31).
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		+	Scientific data suggest that the biological behavior of HSA may vary according to the tissue of origin (4,5,10,24–26). Dogs with dermal HSA may experience prolonged survival or be cured after surgical excision compared with dogs with HSA in other anatomic locations (10). On the contrary, dogs with visceral HSA usually die within a year despite adequate local and systemic treatments (1,13–16). When compared to HSA located in the spleen, right atrium, and liver, primary renal HSA has been associated with a less aggressive disease while retroperitoneal HSA has been associated with a poor clinical outcome due to the high percentage of dogs presenting with metastases at the time of diagnosis (25,26). In contrast to previous studies, our study did not find that primary tumor location influenced prognosis. One possible explanation for this lack of correlation between primary tumor location and survival time is the heterogenous population of dogs in our study. The most common primary organ affected was the spleen, accounting for 81.1% (30/37) of cases. Other primary sites affected were underrepresented, including liver (2/37, 5.4%), kidneys (2/37, 5.4%), intestines (1/37, 2.7%), urinary bladder (1/37, 2.7%), and lymph node (1/37, 2.7%). The absence of significant difference in outcome among dogs diagnosed with HSA located at different primary sites may represent a false-negative result due to a type II error related to the small sample size of the study (32). Therefore, it is not possible to establish definitive conclusions on the importance of primary tumor location of HSA based on our study.
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	Kaplan-Meier curves were created for all 23 dogs treated with surgery alone and for dogs treated with surgery and single agent doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and dogs treated with surgery and adjuvant doxorubicin (P = 0.042) (Figure 2). Median survival time of dogs treated with surgery alone was 66 d (range: 7 to 1075 d), whereas the MST of dogs treated with surgery followed by doxorubicin was 274 d (range: 202 to > 1747 d).		Kaplan-Meier curves were created for all 23 dogs treated with surgery alone and for dogs treated with surgery and single agent doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and dogs treated with surgery and adjuvant doxorubicin (P = 0.042) (Figure 2). Median survival time of dogs treated with surgery alone was 66 d (range: 7 to 1075 d), whereas the MST of dogs treated with surgery followed by doxorubicin was 274 d (range: 202 to > 1747 d).
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		+	<br>
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		+	=== 存活时间 (Survival time) ===
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		+	在数据分析时，有26只狗死亡（13只被安乐死），11只狗还活着。没有一只狗进行尸检以确认它们死于HSA;然而，与HSA相关的死因是根据体格检查结果、胸片和/或腹部超声来推测的。
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		+	所有 37 只狗都被纳入总体生存分析，其中 13 只狗被审查。11只狗在数据分析时还活着，2只狗因丢失而失踪。被诊断患有内脏HSA的狗的总MST为179天（范围：1至>1747天），1年生存率估计为29.2%（图3）。
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		+	At the time of data analysis, 26 dogs had died (13 had been euthanized) and 11 dogs were alive. None of the dogs had postmortem examinations to confirm that they had died of HSA; however, the cause of death related to HSA was presumed on the basis of physical examination findings, thoracic radiographs, and/or abdominal ultrasounds.
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		+	All 37 dogs were included in the overall survival analysis, with 13 dogs censored. Eleven dogs were censored since they were alive at the time of data analysis and 2 dogs due to being lost to follow-up. The overall MST for dogs diagnosed with visceral HSA was 179 d (range: 1 to > 1747 d) and the 1-year survival rate was estimated to be 29.2% (Figure 3).

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