1、Clinical Management of Common Canine Tumors犬常见肿瘤的临床治疗G.Neal Mauldin,DVMDACVIM(Internal Medicine and Oncology)DACVR(Radiation Oncology)Lymphoproliferative Diseases淋巴细胞增生性疾病 Lymphoma淋巴瘤 B-cell,T-cell Multiple Myeloma多发性骨髓瘤 B-cell Plasmacytoma浆细胞瘤 skeletal,extra-skeletal 骨骼的，骨骼外的 Leukemia白血病 acute lymp
2、hoblastic急性淋巴细胞白血病 chronic lymphocytic慢性淋巴细胞白血病Canine Lymphoma犬淋巴瘤 commonly diagnosed malignancy in dogs 在犬通常诊断为恶性incidence 24/100,000 发病率24/100,000 etiology unknown 机理不明genetic predisposition 遗传素质 Bull Mastiff,Golden Retriever 马士提夫犬，金色寻回猎犬environmental toxins 周围环境中的毒素 2,4-DRetrovirus 反转录病毒Canine Ly
3、mphoma犬淋巴瘤Clinical Signs临床症状 peripheral lymphadenopathy 周围淋巴结病 anorexia and lethargy 厌食、乏力 weight loss 体重减轻 evidence of hemorrhage 有出血的表现 dyspnea 呼吸困难 polyuria and polydipsia多尿、多饮 vomiting and diarrhea 呕吐、拉稀Canine Lymphoma犬淋巴瘤Clinical Evaluation临床评估 physical examination findings 临床检查所见peripheral lym
4、phadenopathy 周围淋巴结病splenomegaly and/or hepatomegaly脾肿大和/或肝肿大abdominal mass 腹部肿块pallor 苍白petechial or ecchymotic hemorrhage淤血点或淤血斑muscle wasting肌肉萎缩pleural or abdominal effusion胸腔或腹腔积液“Typical”Presentation典型表现Canine Lymphoma犬淋巴瘤Canine Lymphoma犬淋巴瘤Unusual Presentations罕见症状Canine Lymphoma犬淋巴瘤Clinical E
5、valuation临床评估 recommended diagnostic testing建议进行的检查诊断complete blood count and biochemical profile全血计数和血液生化检测Urinalysis尿液分析Knotts test for microfilaria那特氏检测微丝蚴chest and abdominal radiographs胸部和腹部X光片Electrocardiogram心电图bone marrow aspirate骨髓穿刺tissue biopsy for histopathology活组织组织病理学检查Pulmonary Mass肺部块
6、状阴影Cytologic Diagnosis of LSA淋巴肉瘤细胞学检查Sanctuary SiteCanine Lymphoma犬淋巴瘤Canine Lymphoma犬淋巴瘤Clinical Staging临床分期Stage I-single node involvement.一期-涉及单个淋巴结Stage II-multiple node involvement on one side of diaphragm.二期-涉及膈单侧的多个淋巴结Stage III-generalized lymph node involvement.三期-涉及全身淋巴结Canine Lymphoma犬淋巴瘤
7、Clinical Staging临床分期Stage IV-stages I through III with liver and/or spleen involvement.四期-一期至三期涉及到肝脏和或脾脏Stage V-stages I through IV with bone marrow involvement.五期 一期至四期，涉及到骨髓substage(a)-no signs of systemic illness 亚期（a）-无全身病变症状substage(b)-signs of systemic illness 亚期（b）-出现全身病变症状Splenic Lymphoma脾淋巴
8、瘤Canine Lymphoma犬淋巴瘤Prognosis预后 multiple factors may affect prognosis多种因素都可能影响预后histologic grade of malignancy恶性肿瘤组织学分级substage of disease疾病亚期Hypercalcemia低血钙response to therapy对治疗的反应chemotherapy protocol化疗方案gender性别 median survival times vary with chemotherapy protocol utilized平均生存期受化疗方案应用的影响Lympho
9、ma&Hypercalcemia淋巴瘤和高血钙 Can be associated with any stage可见于任何分期 Many have mediastinal form or bone marrow involvement 很多涉及到纵膈的形式或者骨髓 Rosenberg,1991 n=37 AMM=43%BM involvement=41%41%涉及骨髓Hypercalcemia and LSA高血钙和淋巴肉瘤Thymic and Bone Marrow胸腺瘤和骨髓瘤Lymphoma&Hypercalcemia淋巴瘤和高血钙 Prognostic importance预后的重要性
10、 negative prognostic factor负面预后因素 Rosenberg,1991 n=37 remission duration(median)；平均缓解期 overall-6 months(25%14 months)全部-6个月(25%14个月)AMM-3 months;no AMM-8 months Weller,1982 n=12 survival time-significantly shorter存活期-明显缩短Canine Lymphoma犬淋巴瘤Chemotherapy化疗Canine Lymphoma犬淋巴瘤Chemotherapy化疗 potential to
11、xicities associated with chemotherapy for lymphoma in dogs化学疗法治疗犬淋巴瘤的潜在毒性myelosuppression and infection or sepsis骨髓抑制和感染或败血症anorexia and lethargy厌食、嗜睡nausea and vomiting恶心、呕吐diarrhea拉稀cardiotoxicity心脏毒性alopecia脱毛Lymphoproliferative disorders淋巴组织增殖性疾病 Disorders of Lymphoid origin cells淋巴样组织细胞疾病 Multi
12、ple Myeloma多发性骨髓瘤 Chronic Lymphocytic Leukemia慢性淋巴细胞白血病 Acute Lymphoblastic Leukemia急性淋巴细胞白血病Multiple Myeloma多发性骨髓瘤 Plasma cell tumor systemic浆细胞肿瘤全身性 Diagnostic criteria:诊断标准：Bone marrow infiltrate with neoplastic plasma cells 骨髓内肿瘤性血细胞浸润 Bence Jones Proteinuria Bence Jones蛋白尿 a subunit of immunogl
13、obulin a-免疫球蛋白 Monoclonal gammopathy单克隆免疫球蛋白病 Lytic bone lesions骨溶解Multiple Myeloma多发性骨髓瘤Multiple Myeloma多发性骨髓瘤 Criteria(2 out of 4)标准（4种中至少2种）IgG or IgA monoclonal gammopathy IgG 或 IgA单克隆免疫球蛋白病 radiographic evidence of osteolytic bone lesions X线片检查显示骨溶解 10%neoplastic plasma cells in BM 骨髓中有 10%肿瘤化的
14、血细胞 Bence Jones proteinuria Bence Jones蛋白尿Monoclonal Gammopathy单克隆免疫球蛋白病 Multiple myeloma多发性骨髓瘤 Waldenstroms Macroglobulinemia Waldenstrom氏巨球蛋白血症 Lymphoma淋巴瘤 CLL慢性淋巴细胞白血病 Plasma cell leukemia 血浆细胞白血病 Extramedullary plasmacytoma 浆细胞瘤 Ehrlichia埃里希体 FIP Amyloidosis淀粉样变性 Occult heartworm disease潜在心丝虫疾病
15、Plasmacytic enterocolitis 浆细胞性结肠炎 Leishmaniasis利什曼病Multiple Myeloma Treatment多发性骨髓瘤-治疗 Chemotherapy化疗 day 1-10Melphalan 0.1mg/kg PO q 24h 1-10天 美法仑 0.1mg/kg 口服 24h一次 day 11Melphalan 0.05mg/kg PO q 24h 11天之后 美法仑 0.05mg/kg 口服 24h一次 day 1-10Pred 15mg/m2 PO q 24h 1-10天 泼尼松 15mg/m2 口服 24h一次 day 11-60Pred
16、 15mg/m2 PO q 48h 11-60天 泼尼松 15mg/m2 口服 48h一次Multiple Myeloma Treatment多发性骨髓瘤-治疗 Radiation therapy 放射疗法 localized disease局部病变 spinal cord compression 脊髓压迫症 neurologic disease 神经系统疾病Multiple Myeloma Prognosis多发性骨髓瘤 预后 Survival-18 months(median)存活期 18个月(平均)Negative prognostic factors 负面预后因素 hypercalce
17、mia高血钙 Bence Jones proteinuria Bence Jones 蛋白尿 extensive skeletal lesions 广泛性骨骼损伤 renal insufficiency 肾功能不足Hyperviscosity Syndrome高粘稠度综合征 Major complication of monoclonal gammopathy 单克隆免疫球蛋白病的主要并发症 dogs:20%with monoclonal gammopathy have HVS 犬：20%单克隆免疫球蛋白病患犬患有高粘稠度综合征 Marked increase in serum viscosi
18、ty血浆粘稠度明显增加 Ostwald viscosimeter Ostwald粘度计 expressed relative to water 相对于水 normal anaplastic carcinomascomplex(differentiated)carcinomas肉瘤退行性癌混合（分化型）癌 Specific histologic diagnosis(ie ductular carcinoma vs acinar adenocarcinoma)is not of prognostic significance特殊组织学诊断（例如腺管癌对腺泡腺癌）没有显著的预后意义Prognosti
19、c Factors:Canine Mammary Tumors预后因素：犬乳腺肿瘤 Growth characteristics生长特性 expansion vs invasion 扩张 对 浸润 More aggressive surgery required for invasive tumors对于浸润瘤，手术时应当更加深入 lymphatic/vascular invasion淋巴/血管浸润 presence increases metastatic potential表现出更多的转移倾向 Estrogen receptor status雌激素受体情况 ER+tumors are mo
20、re well differentiated雌激素受体+肿瘤分化良好 Early OHE affects incidence早期绝育影响发病率Prognostic Factors:Canine Mammary Tumors预后因素：犬乳腺肿瘤Stage of disease important 疾病的分期非常重要Factors warranting a worse prognosis:证明较差预后的因素 large,poorly defined tumors 大的，分界不明显的肿瘤 skin involvement牵涉皮肤 lymphatic/distant metastasis 淋巴/远距离
21、转移 histologic grading组织学分级 simple vs complex 单一 或混合 difficult to do,no consistent results reported分级困难，报道的结果不统一Treatment:Canine Mammary Tumors治疗：犬乳腺肿瘤 Surgery!手术 treat all as if malignant所有的恶性肿瘤 remove and biopsy all tumors present去除所有可见的肿瘤并且进行活组织检查 submit entire specimen将整个样品送检 Mammary lymphatic dr
22、ainage:乳腺淋巴管 glands 1&2;axillary lymph node 第 1和2对乳腺 腋窝淋巴结 glands 4&5,inguinal lymph node 第4和5对乳腺 腹股沟淋巴结 gland 3?第3对乳腺？Treatment:Canine Mammary Tumors治疗：犬乳腺肿瘤First surgery is the best surgery首次手术是最佳的手术 avoid simple mastectomy,lumpectomy避免简单的乳腺切除术，病灶切除术 plan surgery using gland number计划手术涉及的腺体数目 radi
23、cal mastectomy?根治性乳房切除术 better to be too aggressive than not aggressive enough过多切除比未彻底根除好Recurrence or regrowth 复发或再生 Definitely needs radical surgery肯定需要彻底的手术治疗Treatment:Canine Mammary Tumors治疗：犬乳腺肿瘤 Complete resection of malignant disease often=cure恶性病变的彻底切除常常=治愈 Incomplete resection of malignant
24、disease:75%death from mammary cancer within 2 years 恶性病变的不完全切除：75%的病例在2年内死于乳腺肿瘤 If complete resection is not possible,then radiation therapy may be used to improve local control 如果不能彻底切除，可以进行放疗进行进一步的局部控制Key Points:Breast Cancer in Companion Animals要点：伴侣动物的乳腺癌 Complete surgical resection best最好进行彻底的手
25、术切除 Early intervention essential早期干预很必要 Treat them all as if they are malignant如果是恶性肿瘤要全部处理 Better to take 1 gland too many than 1 too few要认 为一个腺体很多而不是很少 Give all tissue to the pathologist 将所有的组织送病理师检验 Treat possible systemic involvement aggressively 彻底的处理可能涉及到的组织Canine Mast Cell Tumors犬肥大细胞瘤 common
26、 tumor in dogs犬常见肿瘤 skin is the most common site皮肤是最常见位点 11-27%of malignant skin tumors 11%-27%恶性皮肤肿瘤 Boxer,Boston Terrier,Bulldog 拳师犬，波士顿犭更犬，牛头犬 mean age of 8.5 years平均年龄8.5岁Mast Cells肥大细胞 Cytoplasmic granules contain:细胞质颗粒包含：Heparin肝素 Histamine组织胺 Eosinophilic chemotactic factor嗜酸性趋化因子 蛋白水解酶Proteo
27、lytic enzymesCanine Mast Cell Tumors Site 犬肥大细胞瘤-位点 Skin-most common site皮肤-最常见位点 50%trunk,40%limbs 50%躯干，40%四肢 10%head and neck 10%头颈部 Visceral-usually metastatic内脏 通常为转移性 spleen,liver,kidney 脾脏，肝脏，肾脏 Other primary sites其它原发位点 larynx,mediastinum,GI tract,LN 喉部，纵膈，小肠，淋巴结Canine Cutaneous Mast Cell Tu
28、mor犬表皮肥大细胞瘤 Dermal表皮 1-10 cm(usually 1500 days 存活 1500 天的%Grade I-93%(28/30)一级 93%(28/30)Grade II-47%(16/36)二级-47%(16/36)Grade III-6%(1/17)三级-6%(1/17)Canine MCT Treatment犬肥大细胞瘤 治疗 Surgical Excision手术切除 If Incomplete Excision若不完全切除 Wider resection广泛切除术 Radiation therapy放疗 Chemotherapy化疗 Combination T
29、herapy联合治疗Canine MCT Chemotherapy犬肥大细胞瘤 治疗 Systemic全身性 Oral口服 Intravenous静脉给药 Intralesional内部损伤Canine MCT-Ancillary Therapy犬肥大细胞瘤 辅助治疗 H2 antagonists H2拮抗剂 cimetidine西咪替丁 ranitidine雷尼替丁 H1 antagonists H1拮抗剂 diphenhydramine苯海拉明Canine MCT Chemotherapy犬肥大细胞瘤 化疗 Glucocorticoids糖皮质激素 Chlorambucil+Glucoco
30、rticoids 苯丁酸氮芥+糖皮质激素 Vinblastine+Cyclophosphamide+Glucocorticoids 长春碱+环磷酰胺+糖皮质激素 L-asparaginase L-天冬酰胺酶 Other 其他Canine MCT Chemotherapy犬肥大细胞瘤 化疗 Intralesional Triamcinolone内部损伤用曲安西龙 1.0 mg/cm tumor diameter 肿瘤直径1.0 mg/cm treatments at 2 week intervals 2周的治疗周期 definitive therapy决定性治疗 prior to surgica
31、l resection在手术治疗前 appropriate for small tumors适合小肿瘤Canine MCT-Survival Data犬肥大细胞瘤 存活期 Radiation Therapy;n=32 dogs放射疗法；Al-Sarraf(JVIM 1996,in press)Cobalt 60;post-op;Grade II;54 Gy 钴60；术后；2级；54格雷 1-year survival rate=100%1年存活率=100%2-5 year survival rate=96%2-5年存活率=96%Soft tissue sarcomas comprise app
32、roximately 15%of all canine“skin”and subcutaneous cancers 犬皮肤和皮下肿瘤几近15%为软组织肉瘤 Annual incidence is approximately 35/100,000 每年的发病率达到35/100,000 Arise from a variety of mesenchymal tissues 由间质组织异变引起 Tumor types include:肿瘤类型包括：fibrosarcomas纤维肉瘤 nerve sheath tumors神经鞘瘤 hemangiopericytomas血管外皮细胞瘤 malignan
33、t fibrous histiocytomas恶性纤维组织瘤 myxosarcomas粘液肉瘤 liposarcomas脂肪肉瘤 Common features of soft tissue sarcomas:软组织肉瘤的共同特征 They may arise from any anatomic site in the body可能起源于身体的任何解剖部位 They tend to appear as pseudoencapsulated fleshy tumors but have poorly defined histologic margins它们表现为假包膜结缔组织肉瘤，但是组织学分界
34、不明显 Local recurrence after conservative surgical excision is common保守手术切除术后常见局部复发 Tend to metastasize through hematogenous methods in up to 25%of cases;regional lymph node metastasis is unusual(except for synovial cell sarcoma)超过25%的病例有通过血液转移的趋势；局部淋巴结转移不常见（滑膜细胞肉瘤除外）Generally have poor response to ch
35、emotherapy and radiation therapy for measurable disease通常对化疗和放疗不敏感 Most reports of treatment to date involve the use of surgery or radiation迄今为止，大多数报道的治疗方式为手术或放疗 Surgery alone for hemangiopericytoma对血管外皮细胞瘤只进行手术治疗 Postern reported a 79%one year control rate Postern报道，一年控制率为79%Graves reported a 31%re
36、currence rate for these tumors Graves报道，31%的复发率 Radiation alone单独放疗 McChesney,et al,1989 reported a 48-67%1 year control rate and a 33%2 year control rate for canine STS 据McChesney,et al,1989报道，犬软组织肉瘤1年控制率为48-67%，2年为33%Radiation and Hyperthermia放疗和高温疗法 McChesney,Gillette,Dewhirst,1992 median time to
37、 recurrence=30 months复发的平均时间为30个月 1 year control rate=approx.79%一年控制率接近79%ResultsSurvival FunctionComplete CensoredSurvival TimeCumulative Proportion Surviving0.650.700.750.800.850.900.951.001.051.100500100015002000250030003500Median survival has not been reached yet平均生存期仍未得出结论75%survival at 5 years
38、 75%5年后仍存活Discussion/Conclusions讨论/结论 75%5 year survival rate 5年存活率75%No correlation between survival and tumor type,anatomic location,or gender存活去肿瘤类型，解剖位置和性别均无关 Only significant factors with respect to survival were development of metastatic disease and time to recurrence关于存活的仅有重要因子为转移性疾病和复发的时间Ost
39、eosarcoma骨肉瘤 Most common primary bone tumor in the dog犬最常见的原发性骨肿瘤 Disease of middle aged to older dogs见于中年至老年犬 Median age 7 years 平均年龄为7岁 small peak in incidence at 18-24 months在18-24月龄间有发病小高峰 Cancer of large and giant breeds大型和巨型犬的肿瘤 appendicular more common in giant breeds巨型犬常见于四肢 axial more commo
40、n in smaller breeds较小型犬常见于躯干OSA骨肉瘤 Metaphysis of long bones长骨干骺端 front limbs twice as often as rear limbs前肢发病率为后肢2倍“Towards the knee and away from the elbow”“向膝盖和远离肘”May see secondary to trauma可继发于外伤 surgical pins/plates外科骨针/骨板 secondary to RT继发于放疗OSA骨肉瘤Metastasis转移 Less than 5%have metastasis at di
41、agnosis诊断时少于5%发生转移 90%+will die of metastasis within 1 year if amputation is the only treatment offered如果截肢术是唯一的治疗方式，超过90%的犬1年后将死于转移 Pulmonary,bone most common最常见转移位置为肺，骨。OSA骨肉瘤Staging分期 Chest radiographs胸部X光片 Primary radiographs原发影像 bone scan?骨部影像 Routine blood tests常规血液检查 Surgical biopsy外科活组织检查 ne
42、edle biopsy细针活检 Incisional切开活检 Amputation截除术OSA骨肉瘤Therapy治疗Hemangiosarcoma 血管肉瘤 Tumor arising from vascular endothelium肿瘤从血管的内皮出现 Tumor of older dogs 老龄犬的肿瘤 8-13 years 8-13岁 Majority occur in large breeds 大多发生于大型犬 German Shepherds over-represented 德国牧羊犬位数较多Hemangiosarcoma血管肉瘤Anatomic location解剖位置 Sp
43、leen is the most common primary site脾脏是最常见的原发位点 most mid-abdominal masses in the dog are splenic犬大多数腹中部的肿物为脾的 Right atrium右心房 Skin and sub-Q皮肤和皮下 Liver肝脏 Bone骨 Anywhere else其他部位HemangiosarcomaClinical Presentation Incidental finding 偶发性的发现 Collapse 衰弱，体力不支 hemoabdomen:may have a history of collapse
44、and recovery 腹部出血：可能有体力不支和恢复的病史 cardiac tamponade：心脏阻塞 DIC and bleeding 弥散性血管内凝血和出血 Mass effect(skin and sub-q)肿物影响（皮肤和皮下）These are frequently metastatic rather than primary 这些通常是转移的而非原发的HemangiosarcomaTreatment 血管肉瘤治疗 Surgery!手术 May have to take a patient in DIC to surgery 可能必须对患有弥散性血管内凝血的病患进行手术 Ch
45、emotherapy 化疗 Most animals are diagnosed at the time of rupture,so most have metastasis when they present 大部分的动物都是在破裂是被诊断出来，所以多数来就诊事都已经有转移的发生治疗存活时间致死因无0 天弥散性血管内凝血，破裂脾切除30 天转移脾切除+阿霉素170-210天转移脾切除+阿霉素+生物调节剂277天转移心耳切除120天转移Transitional Cell Carcinoma 移行细胞癌 Most common bladder cancer 常见于膀胱癌 Older dogs 老
46、龄犬 median age of 10 years 平均年龄约10岁 More common in female dogs 多发生于母犬 mimics cystitis 僞膀胱炎 frequently presents at an advanced stage after weeks-months of conservative therapy 多发生于接受保守治疗的进阶阶段数周或数月后Transitional Cell Carcinoma Lower urinary tract signs 下泌尿道症状 hematuria,dysuria,血尿，多尿 stranguria,pollakiur
47、ia 淋证，频尿 Routine diagnostics frequently unremarkable 一般检查通常无明显异常 May see neoplastic cells on U/A 可以在超声上看到肿瘤细胞 Ultrasound or contrast radiographs 超声或放射显影Transitional Cell Carcinoma Aggressive local and systemic behavior 积极的局部和全身行为 metastasis to liver,lung,regional lymph nodes,pelvis 转移到肝，肺，淋巴结区，耻骨 Ma
48、ny patients(50%)have metastasis at the time of presentation 多数的病患（50%）在发现是都已经有转移Transitional Cell CarcinomaSurgical Resection 手术切除 trigonal location 三角位置 Metastatic 转移Chemotherapy 化疗 150-240 days 150-240 天 Adriamycin may increase survival 400 days亚德里亚霉素（阿霉素）可以增加400天的存活时间 Radiation 放射治疗 good local control,no therapy for mets,poor residual bladder function 良好的局部控制，无法做转移的治疗，损伤肾脏的功能Piroxicam 吡罗昔康 NSAID,not cytotoxic 非类固醇类抗炎药，肺细胞毒作用 Median survival(6 dogs)of 181 days 生存中间值（6只犬）为181天 Control of inflammation?Antiangiogenic?炎症的控制？抗血管增生？
