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1、Diagnosis and Treatment of Ovarian Cancer,Shen Keng Department of OB/GYNPeking Union Medical College Hospital,Epidemiology and Genetic Factors,Ovarian cancer is the second most common gynecological malignancy,but the commonest malignancy of the female genital tract to result in deathIncidence:In gen
2、eral population lifetime risk for ovarian cancer in a women is roughly 1/70 or 1.4%.,Epidemiology and Genetic Factors,The incidence in Asia,Africa and Latin America is lower than in Western countries.The most common tumor type is epithelial(85%).,卵巢癌的危险因素,年龄,危险因素,与子宫内膜、结肠、乳腺癌的关系,家庭史,生产史和激素水平,Epidemi
3、ology and Genetic Factors,High risk factors:1.More than 40yrs.2.Caucasian race(white)3.Late menopause.4.Infertility 5.Positive family history of CA ovary 6.BRCA gene,Epidemiology and Genetic Factors,Family history is the strongest risk factor for ovarian cancer Women with one affected first class re
4、lative:risk rate for ovarian cancer is 5%Women with two affected first class relative:risk rate for ovarian cancer is 7%A member of HOCS:risk rate for ovarian cancer is 20%-50%BRCA1&BRCA2 gene associated with HOCS,Epidemiology and Genetic Factors,Prevention&protective factors for ovarian cancer appe
5、ar to be conditions associated with fewer lifetime ovulations 1.Use of oral contraceptive pills 2.Shorter duration of reproductive years 3.Conditions of chronic anovulation 4.History of breastfeeding 5.Multiparity,Histopathology,Epithelial ovarian cancer,usually classed simply as adenocarcinoma,incl
6、ude a number of specific histological types:Serous adenocarcinomaMuconous adenocarcinomaEndometrioid adenocarcinomaMalignant Brenner tumor(transitional cell)Clear cell adenocarcinoma,Histopathology,Malignant Germ Cell Tumor of the Ovary include a number of specific histological types:DysgerminomaYol
7、k-Sac Tumor(endodermal sinus tumor)TeratomasChoriocarcinomaMixed germ cell tumor,Histopathology,Malignant Tumor of the Gonadal stroma:Granulosal-cell tumors Adult type Juvenile typeSertoli-cell tumorsLeydig-cell tumorsSertoli-Leydig-cell tumorsSex cord tumor with annular tubules,Spread of ovarian ca
8、ncer,Local spreadIntra-abdominal spreadlymphatic spreadhemtogenous spread,Symptoms,Symptoms are most often absent with early stage ovarian cancer.When present,symptoms tend to be nonspecificGI tract complaints:such as nausea,abdominal cramping,or change in bowel habits,are often the early symptoms o
9、f advanced stage disease.By this time,the disease may be widely disseminated throughout the peritoneal cavityAbdominal distention:big mass,omental cake,ascites intestinal obstruction,Symptoms,Postmenopausal bleeding may occur from endometrial hyperplasia stimulated by estrogen from a ovarian tumor.V
10、irilization is found in 50%of patients who have an androgen-secreting Sertoli-Leydig-cell tumor.Colicky pain is associated with torsion of a mobile ovarian tumor.Constant pain may be experienced with the distention of hemorrhage into a tumor,Physical examination,Fixed,bilateral pelvic massesAbdomina
11、l mass:omental cake,big ovarian tumorAbdominal percussion:ascitesA nodular tumor in PODPleural effusion Meiges syndrome consists of ascites and hydrothorax associated with fibroma and thecoma.,Preoperative workup,Pap smear(f)D&CTumor makers:CA125,CEA,HCG,AFP,LDHChest film to look for lung metastasis
12、 and pleural effusion,Preoperative workup,Barium enema to evaluate the lower GI tractPlain film of the abdomen to identify intestinal obstruction IVP to assess the urinary systemUSG,CT scan or MRI to determinate the anatomy relationship between the ovarian cancer and pelvic organs,卵巢癌的MRI,Courtesy o
13、f Barry N.Siskind,MD,The Graduate Hospital Imaging Center,Philadelphia,PA,USA,子宫,卵巢 肿块,直肠,Preoperative workup,Peritoneocentesis for reliving abdominal distention and cytology examination.Laparoscopy can be used to obtained pathological diagnosis of ovarian cancer preoperatively,The role of Surgery i
14、n the management of ovarian cancer,Diagnostic Establish diagnosis and determine histology and grade of the tumor Surgical staging Reassessment Laparotomy Therapeutic Primary cytoredution Secondary cytoreduction Provision of intravenous and intraperitonel accessPalliative Reduction of tumor bulk,Reli
15、eve gastrointestinal obstruction,Surgeries for ovarian cancer,Comprehensive staging laparotomyRestaging laparotomyPrimary cytoreductive surgeryInterval debulkingSecond-look laparotomySecond debulking(Recytoreductive surgery),Standard procedure of cytoreductive surgery for ovarian cancer,Longitudinal
16、 incisionAbdominal fluid for cytology ExplorationOmentectomyTotal hysterectomyBilateral salpingo-oohporectomyPara-aortic and pelvic lymphadenectomyLow anterior resection of colonAppendectomy,卵巢癌的临床分期,卵巢癌I期和II期,卵巢癌III期和IV期,Beecham Sevigne,M閙ento de Stadification des Principales Tumeurs Solides,III期,种
17、植性肝转移,腹腔腹膜转移,肝实质性转移,恶性胸膜细胞,前锁骨淋巴结,IV期,卵巢癌的治疗:手术(I),DeVita et al.Cancer:Principles&Practice of Oncology.1993,全腹腔探查和活检,网膜,几乎所有的病人进行全子宫、双侧输卵管及网膜切除术,Lymph nodes metastasis and retroperitonal lymphadenectomy in ovarian cancer,Lymphatic pathway is an important route of metastasis in ovarian cancer.The ove
18、rall incidence of retroperitoneal positive nodes 54.3%The incidence of positive pelvic nodes 46.7%positive para-aortic nodes 37.5%Both aortic and pelvic nodes positive 48.7%,Intestinal metastasis and operation in ovarian cancer,Rectosigmoid involved 95.2%Metastasis to small bowel 41.9%Superficial an
19、d serosal invasion 64.5%Complete or optimal resection 74.2%resection of the bowel 31.2%Colostomy 9.8%27.4%survival with mean survival time 30.3 months,Conservative surgery in ovarian cancer,Germ cell tumor(any stage)Stage I grade I granulosal cell tumor For epithelial cancer:1.Young patient and desi
20、re of reproduction 2 Stage Ia,3.Grade 1 4.Capsule intake 5.No adhesion 6.Peritoneal cytology negative 7.Multiple biopsies of high risk negative 8.Follow up available,Management of Ovarian Cancer,Early diseaseStage IA/B grade I/IIexploratory operation;conservative resectionpreserve fertility in bilat
21、eral borderline tumours adjuvant therapy unprovenUnfavourable typepoorly differentiated clear cell tumourscapsule penetrationruptured capsulepositive washingsstage II:standard operation+adjuvant therapy,早期卵巢癌的化疗,FIGO I，II期卵巢癌“预后好”的患者90%以上可长期无瘤存活，而且不需要辅助化疗。有高危因素的患者，30%-40%有复发的危险，25%-30%在首次手术后5年内死亡。与复
22、发有关的高危因素：（1）包膜破裂（2）肿瘤表面生长（3）低分化（G3）（4）与周围组织粘连（5）透明细胞癌（6）腹腔冲洗液阳性（7）卵巢癌外转移,Management of Ovarian Cancer,Advanced stage diseaseStage III/IV Primary cytoreductive surgery/interval debulking Obtained optimal debulkung(residual tumor 6 months)-secondary debunking following chemotherapy Palliative treatmen
23、t(Radiotherapy,immunotherapy)unproven,Chemotherapy in ovarian cancer,First line chemotherapy for epithelial ovarian cancer CHexUP and Thio-Tepa protocol(1982-1985)PAC or PC(1986-1990)DDP,5-FU,Ara-c,Bleomycin,CTX.IP&IV Combination(1991-1994)Taxol,DDP/Carpa(1995-2000)Weekly taxol/Carpa(2000-),Combinat
24、ion Chemotherapy,Cisplatin acts by binding to DNA and producing cross-links and DNA adducts.Cisplatin is a very effective drug for ovarian cancer.Important side effects include severe nausea and vomiting,dose-related nephrotoxicity,ototoxicity,peripheral nerutoxicity and myelosuppresion,Combination
25、Chemotherapy,The mechanism of action of carboplatin is the same as that of cisplatin,the side effects,however,differ greatly.The most important side effect is thrombocytopenia.Leukopenia and anemia also occur but are less severe.Neurotoxicity and nephrotoxicity are less severe with carboplatin than
26、with cisplatinOther important side effect include alopecia and mucositis.,Combination Chemotherapy,Paclitaxel acts as a mitotic spindle poison.Paclitaxel is also a very effective drug for ovarian cancer at the present timeSome patients exhibit hypersensitivity to paclitaxel.Other side effect include
27、 myelosuppression,nerotoxicity,mucositis,diarrhea,alopcia nausea and vomiting,卵巢上皮癌的化疗,铂基础治疗方案通常联合:紫杉醇环磷酰胺 阿霉素通常需要间隔3-4周至少6个周期的治疗,晚期卵巢癌的化疗,一线治疗国内顺铂+环磷酰胺(PC)顺铂+阿霉素+环磷酰胺(PAC)国外泰素顺铂泰素卡铂泰素每周疗法,Combination Chemotherapy,Combination chemotherapy most often is used as postoperative treatment for advanced ep
28、ithelial ovarian cancer.Combination chemotherapy with six courses of cisplatin or carboplatin plus paclitaxel is the treatment of choice for patients with advanced disease.Courses are given every 3 to 4 weeks with monitoring of tumor status by physical examination.CA125 levels,and imaging studies if
29、 appropriate,卵巢癌病人化疗存活率,McGuire WP et al.N Engl J Med.1996,Post-Therapy Surveillance,Follow-up after therapy in ovarian cancer is poorly defined.At the present time there is no definitive test for detecting the presence of microscopic recurrent epithelial ovarian cancerFor this reason there remains
30、significant controversy as to what constitutes optimal posttherapy surveillance.,Post-Therapy Surveillance,Screening modalities:1.Pelvic Examination 2.CA 125(44%sensitivity,96%specificity,65%accuracy)3.Ultrasound(20%-89%sensitivity,75%-100%specificity)4.Second-look laparotomy 5.CT scan(44%sensitivit
31、y,86%specificity,63%accuracy)6.MIR imaging.6.Position emission tomography(PET)(83%sensitivity,80%specificity,82%accuracy),卵巢癌复发的诊断和治疗,首次的规范化治疗(理想的肿瘤细胞减灭术加上以足够疗程的铂类和/或紫杉醇为基础的联合化疗)70%-80%的患者可获得临床完全缓解.60%-70%的患者最终还会复发.对卵巢癌复发的诊断和治疗是卵巢癌治疗中最为棘手的问题.怎样合理处理复发性卵巢癌意见尚不统一,卵巢癌的复发类型(1),化疗敏感型卵巢癌:定义为对初期以铂类药物为基础的治疗有
32、明确反应,且已经达到临床缓解,停用化疗6个月以上,病灶复发.,卵巢癌的复发类型(2),化疗耐药型卵巢癌:定义为患者对初期的化疗有反应,但在完成化疗相对短的时间内证实复发,一般认为,完成化疗后6个月内的复发,应考虑为铂类药物耐药,卵巢癌的复发类型(3),顽固性卵巢癌:是指在初期化疗时对化疗有反应或明显反应的患者中发现有残余病灶,例如:“二探”阳性者.,卵巢癌的复发类型(4),难治性卵巢癌:是指对化疗没有产生最小有效反应的患者,包括在初始化疗期间,肿瘤稳定或肿瘤进展者,大约发生于20%的患者.这类患者对二线化疗的有效反应率最低.,卵巢癌复发的治疗,治疗前的准备:详细复习病史包括:(1)手术分期.(
33、2)组织学类型和分级.(3)手术的彻底性.(4)和残余瘤的大小及部位.(5)术后化疗的方案,途径,疗程,疗效.(6)停用化疗的时间.(7)出现复发的时间等.对复发性卵巢癌进行定性、分型、定位分析对患者的生活状态(PS)进行评分,对患者重要器官的功能进行评估.,目前观点认为:对于复发性卵巢癌的治疗目的一般是趋于保守性的,因此在选择复发性卵巢癌治疗方案时,对所选择方案的预期毒性作用及其对整个生活质量的影响都应该加以重点考虑.,复发性卵巢癌的手术治疗,手术对复发性卵巢癌的治疗价值尚未确定,手术的指征和时机还存在一些争论.复发性卵巢癌的手术治疗主要用于三个方面:1.解除肠梗阻 2.12个月复发灶的减灭
34、.3.切除孤立的复发灶.对晚期复发卵巢癌是先手术还是先化疗仍有争议.,Chemotherapy in Ovarian Cancer,Second line chemotherapy for epithelial ovarian cancer Patients with persistent or recurrent diseases should be treated with second line chemotherapy.Unfortunately,response rates for second line chemotherapy are only 10%to 30%.Regardi
35、ng of the approach,second line chemotherapy for persistent or recurrent ovarian cancer is not curative.,Second line chemotherapy for epithelial ovarian cancer Depending on the initial chemotherapy,second line chemotherapy may include:Topotecan Paclitaxel Platinum Ifosfamide Taxotere Hexamethylmelami
36、ne,Combination Chemotherapy,对复发卵巢癌有效的新药,Survival,Early-stage diseaseFive year survival rate for patients with stage I or stage II disease are 80%to 100,depending on the tumor gradeAdvanced disease Five year survival rate for patients with stage IIIa is 30%to 40%Five year survival rate for patients w
37、ith stage IIIb is 20%Five year survival rate for patients with stage IIIc or IV is 5%Recurrent diseaseFive year survival rate for patients with negative SLL is 50%Five year survival rate for patients with microscopic disease is 35%Five year survival rate for patients with macroscopic disease is 5%,M
38、alignant Germ Cell Tumor of the Ovary,Twenty percent to 25%of all malignant tumor of the ovary are of germ cell origin.In the first decades of life,70%of ovarian tumors are of germ cell origin and one third are malignantGerm cell tumors are quite rare after the third decades of life.,1.Malignant ger
39、m cell tumor of the ovary is very sensitive to the chemotherapy.Chemotherapy has been a very important treatment for this kind ovarian tumor.2.Chemotherapy has improved the survival of patients with Malignant germ cell tumor of the ovary dramatically.Survival rate has been increased from 10%to 90%3.
40、Reproductive function can be preserved for any stage patients with malignant germ cell tumor of the ovary,Malignant Germ Cell Tumor of the Ovary,Management of malignant germ cell tumor of the ovary,Primary treatment is surgical.Unilateral oophorectomy with preserved reproductive function is consider
41、ed.PVB and PEB chemotherapy are the treatment of choice for patients with MGCT postoperativelyCourses of chemotherapy are depending on the high risk factors of the tumor and tumor maker levels,Sex cord stromal tumors,Ovarian sex cord-stromal tumor account for less than 5%.It may occur at any age,alt
42、hough the age of peak incidence for granular cell tumors is in the postmenopausal years.No standard therapy exists.Lower malignant potential and late recurrence,Sex cord stromal tumors,Surgery remains cornerstone of treatment for patients with ovarian sex cord stromal tumors.95%of the tumor are unil
43、ateral,95%are confined to the ovary.Unilateral salpingo-oophorectomy seems to appropriate treatment for young patients with stage Ia disease.THBSO is considered standard surgery for old patients and advanced stage diseases.,Sex cord stromal tumors,PVB chemotherapy is the treatment of choice for sele
44、cted patient with sex cord stromal tumor after surgical treatment.Long term follow-up should be considered for this kind of tumor because of late recurrence.The 10 year survival rate is 90%,and the 20 year survival rate drop to 75%.,Sex cord stromal tumors Prognostic factors,Stage(extraovary metastasis)Tumor sizeHistologic typeMitotic countAtypiaDNA ploidy(associated with other adverse histolopathologic parameters)High stage,vascular invasion,nuclear atypia,high mitotic activity plus aneuploidy poor prognosis,
