卵巢癌的診斷和治療醫(yī)大講課

1、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 general population lifetime ri

2、sk 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%

3、).,卵巢癌的危險(xiǎn)因素,,,,,年齡,危險(xiǎn)因素,與子宮內(nèi)膜、結(jié)腸、乳腺癌的關(guān)系,家庭史,生產(chǎn)史和激素水平,Epidemiology and Genetic Factors,High risk factors: 1. More than 40yrs. 2. Caucasian race (white) 3. Late menopause. 4. Infertility

4、 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 relative: risk rate for o

5、varian 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

6、 Genetic Factors,Prevention & protective factors for ovarian cancer appear to be conditions associated with fewer lifetime ovulations 1. Use of oral contraceptive pills 2. Shorter duration of reproductive

7、 years 3. Conditions of chronic anovulation 4. History of breastfeeding 5. Multiparity,Histopathology,Epithelial ovarian cancer, usually classed simply as adenocarcinoma, include a number of specific hi

8、stological types:Serous adenocarcinomaMuconous adenocarcinomaEndometrioid adenocarcinomaMalignant Brenner tumor (transitional cell)Clear cell adenocarcinoma,Histopathology,Malignant Germ Cell Tumor of the Ovary incl

9、ude a number of specific histological types:DysgerminomaYolk-Sac Tumor (endodermal sinus tumor)TeratomasChoriocarcinomaMixed germ cell tumor,Histopathology,Malignant Tumor of the Gonadal stroma:Granulosal-cell tumo

10、rs Adult type Juvenile typeSertoli-cell tumorsLeydig-cell tumorsSertoli-Leydig-cell tumorsSex cord tumor with annular tubules,Spread of ovarian cancer,Local spreadIntra-abdominal spreadlymphatic sp

11、readhemtogenous 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 bowe

12、l habits,are often the early symptoms of advanced stage disease. By this time, the disease may be widely disseminated throughout the peritoneal cavityAbdominal distention: big mass, omental cake, ascites intestinal obst

13、ruction,Symptoms,Postmenopausal bleeding may occur from endometrial hyperplasia stimulated by estrogen from a ovarian tumor.Virilization is found in 50% of patients who have an androgen-secreting Sertoli-Leydig-cell tum

14、or.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 massesAbdominal mass: o

15、mental cake, big ovarian tumorAbdominal percussion: ascitesA nodular tumor in PODPleural effusion Meige’s syndrome consists of ascites and hydrothorax associated with fibroma and thecoma.,Preoperative workup,Pap smea

16、r(f) D&CTumor makers: CA125, CEA, HCG, AFP, LDHChest film to look for lung metastasis and pleural effusion,Preoperative workup,Barium enema to evaluate the lower GI tractPlain film of the abdomen to identif

17、y 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 of Barry N. Siskind, MD, The Graduate

18、Hospital Imaging Center, Philadelphia, PA, USA,子宮,卵巢 腫塊,直腸,Preoperative workup,Peritoneocentesis for reliving abdominal distention and cytology examination.Laparoscopy can be used to obtained pathological diagnosis of o

19、varian cancer preoperatively,The role of Surgery in the management of ovarian cancer,Diagnostic Establish diagnosis and determi

20、ne histology and grade of the tumor Surgical staging R

21、eassessment Laparotomy Therapeutic Primary cytoredution

22、Secondary cytoreduction Provision of intravenous and intraperitonel accessPalliative

23、 Reduction of tumor bulk, Relieve gastrointestinal obstruction,Surgeries for ovarian cancer,Comprehensive staging laparotomyRestaging laparotomyPrimary cytoreductive surgeryInterval debulki

24、ngSecond-look laparotomySecond debulking (Recytoreductive surgery),Standard procedure of cytoreductive surgery for ovarian cancer,Longitudinal incisionAbdominal fluid for cytology ExplorationOmentectomyT

25、otal hysterectomyBilateral salpingo-oohporectomyPara-aortic and pelvic lymphadenectomyLow anterior resection of colonAppendectomy,卵巢癌的臨床分期,卵巢癌I期和II期,,卵巢癌III期和IV期,Beecham Sevigne, M閙ento de Stadification des Principal

26、es Tumeurs Solides,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,III期,種植性肝轉(zhuǎn)移,腹腔腹膜轉(zhuǎn)移,,,,,,,肝實(shí)質(zhì)性轉(zhuǎn)移,惡性胸膜細(xì)胞,前鎖骨淋巴結(jié),IV期,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

27、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,卵巢癌的治療: 手術(shù) (I),DeVita et al. Cancer: Principles & Practice of Oncology.1993,全腹腔探查和活檢,網(wǎng)膜,幾乎所有的病人進(jìn)行全子宮、雙側(cè)輸卵管及網(wǎng)膜切除術(shù),Lymph nodes

28、 metastasis and retroperitonal lymphadenectomy in ovarian cancer,Lymphatic pathway is an important route of metastasis in ovarian cancer.The overall incidence of retroperitoneal positive nodes 54.3% The incidence of p

29、ositive 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% Me

30、tastasis to small bowel 41.9% Superficial and serosal invasion 64.5% Complete or optimal resection 74.2% resection of the bowel

31、 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 granulo

32、sal cell tumor For epithelial cancer : 1. Young patient and desire of reproduction 2 Stage Ia, 3. Grade 1 4. Capsule intake 5. No adhesion 6. Peritoneal cytology ne

33、gative 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 bi

34、lateral borderline tumours adjuvant therapy unprovenUnfavourable typepoorly differentiated clear cell tumourscapsule penetrationruptured capsulepositive washingsstage II: standard operation + adjuvant therapy,早期卵巢

35、癌的化療,FIGO I，II期卵巢癌“預(yù)后好”的患者90%以上可長(zhǎng)期無瘤存活，而且不需要輔助化療。有高危因素的患者，30%-40%有復(fù)發(fā)的危險(xiǎn)，25%-30%在首次手術(shù)后5年內(nèi)死亡。與復(fù)發(fā)有關(guān)的高危因素： （1）包膜破裂 （2）腫瘤表面生長(zhǎng) （3）低分化（G3）（4）與周圍組織粘連 （5）透明細(xì)胞癌

36、 （6）腹腔沖洗液陽性 （7）卵巢癌外轉(zhuǎn)移,Management of Ovarian Cancer,Advanced stage diseaseStage III/IV Primary cytoreductive surgery / interval debulking Obtained optimal debulkung (residual tumor 6 months)---secondary debunking foll

37、owing chemotherapy Palliative treatment (Radiotherapy, immunotherapy) unproven,Chemotherapy in ovarian cancer,First line chemotherapy for epithelial ovarian cancer CHexUP and Thio-Tepa protocol ( 1982

38、-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--),Combination Chemotherapy,Cisplatin acts by binding to DN

39、A 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 nerutox

40、icity and myelosuppresion,Combination 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. L

41、eukopenia and anemia also occur but are less severe.Neurotoxicity and nephrotoxicity are less severe with carboplatin than with cisplatinOther important side effect include alopecia and mucositis.,Combination Chemother

42、apy,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 myelosuppr

43、ession , nerotoxicity, mucositis, diarrhea, alopcia nausea and vomiting,卵巢上皮癌的化療,鉑基礎(chǔ)治療方案通常聯(lián)合:紫杉醇環(huán)磷酰胺 阿霉素通常需要間隔3- 4周至少6個(gè)周期的治療,晚期卵巢癌的化療,一線治療國(guó)內(nèi)順鉑+環(huán)磷酰胺(PC)順鉑+阿霉素+環(huán)磷酰胺(PAC)國(guó)外泰素＋順鉑泰素＋卡鉑泰素每周療法,Combination Chemotherap

44、y,Combination chemotherapy most often is used as postoperative treatment for advanced epithelial ovarian cancer. Combination chemotherapy with six courses of cisplatin or carboplatin plus paclitaxel is the treatment of

45、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 appropriate,卵巢癌病人化療存活率,,McGuire WP et al. N E

46、ngl 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 ovar

47、ian cancerFor this reason there remains significant controversy as to what constitutes optimal posttherapy surveillance.,Post-Therapy Surveillance,Screening modalities: 1. Pelvic Examination 2. CA 125 (44%

48、sensitivity, 96% specificity, 65% accuracy) 3. Ultrasound (20%-89% sensitivity, 75%-100% specificity) 4. Second-look laparotomy 5. CT scan (44% sensitivity, 86% specificity, 63% accuracy) 6. MIR

49、 imaging. 6. Position emission tomography (PET) (83% sensitivity, 80% specificity, 82% accuracy),卵巢癌復(fù)發(fā)的診斷和治療,首次的規(guī)范化治療(理想的腫瘤細(xì)胞減滅術(shù)加上以足夠療程的鉑類和/或紫杉醇為基礎(chǔ)的聯(lián)合化療) 70%-80%的患者可獲得臨床完全緩解.60%-70%的患者最終還會(huì)復(fù)發(fā).對(duì)卵巢癌復(fù)發(fā)

50、的診斷和治療是卵巢癌治療中最為棘手的問題.怎樣合理處理復(fù)發(fā)性卵巢癌意見尚不統(tǒng)一,卵巢癌的復(fù)發(fā)類型 (1),化療敏感型卵巢癌: 定義為對(duì)初期以鉑類藥物為基礎(chǔ)的治療有明確反應(yīng),且已經(jīng)達(dá)到臨床緩解,停用化療6個(gè)月以上,病灶復(fù)發(fā).,卵巢癌的復(fù)發(fā)類型 (2),化療耐藥型卵巢癌: 定義為患者對(duì)初期的化療有反應(yīng),但在完成化療相對(duì)短的時(shí)間內(nèi)證實(shí)復(fù)發(fā),一般認(rèn)為,完成化療后6個(gè)月內(nèi)的復(fù)發(fā),應(yīng)考慮為鉑類藥物耐藥,卵巢癌的復(fù)發(fā)類型(3),頑固性卵

51、巢癌: 是指在初期化療時(shí)對(duì)化療有反應(yīng)或明顯反應(yīng)的患者中發(fā)現(xiàn)有殘余病灶,例如:“二探”陽性者.,卵巢癌的復(fù)發(fā)類型 (4),難治性卵巢癌: 是指對(duì)化療沒有產(chǎn)生最小有效反應(yīng)的患者,包括在初始化療期間,腫瘤穩(wěn)定或腫瘤進(jìn)展者,大約發(fā)生于20%的患者. 這類患者對(duì)二線化療的有效反應(yīng)率最低.,卵巢癌復(fù)發(fā)的治療,治療前的準(zhǔn)備:詳細(xì)復(fù)習(xí)病史包括: (1)手術(shù)分期. (2)組織學(xué)類型和分級(jí). (3)手術(shù)的徹底性. (4)和殘余

52、瘤的大小及部位. (5)術(shù)后化療的方案,途徑,療程,療效. (6)停用化療的時(shí)間. (7)出現(xiàn)復(fù)發(fā)的時(shí)間等.對(duì)復(fù)發(fā)性卵巢癌進(jìn)行定性、分型、定位分析對(duì)患者的生活狀態(tài)(PS)進(jìn)行評(píng)分,對(duì)患者重要器官的功能進(jìn)行評(píng)估.,目前觀點(diǎn)認(rèn)為: 對(duì)于復(fù)發(fā)性卵巢癌的治療目的一般是趨于保守性的, 因此在選擇復(fù)發(fā)性卵巢癌治療方案時(shí),對(duì)所選擇方案的預(yù)期毒性作用及其對(duì)整個(gè)生活質(zhì)量的影響都應(yīng)該加以重點(diǎn)考慮.,復(fù)發(fā)性卵巢癌的手術(shù)治療,手術(shù)對(duì)復(fù)發(fā)性卵巢癌的治療價(jià)

53、值尚未確定, 手術(shù)的指征和時(shí)機(jī)還存在一些爭(zhēng)論.復(fù)發(fā)性卵巢癌的手術(shù)治療主要用于三個(gè)方面: 1.解除腸梗阻 2.>12個(gè)月復(fù)發(fā)灶的減滅. 3.切除孤立的復(fù)發(fā)灶.對(duì)晚期復(fù)發(fā)卵巢癌是先手術(shù)還是先化療仍有爭(zhēng)議.,Chemotherapy in Ovarian Cancer,Second line chemotherapy f

54、or 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%.

55、Regarding 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

56、, second line chemotherapy may include: Topotecan Paclitaxel Platinum

57、 Ifosfamide Taxotere Hexamethylmelamine,Combination Chemotherapy,對(duì)復(fù)發(fā)卵巢癌有效的新藥,Survival,Early-stage diseaseFive year survival rate for patients

58、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 with stage IIIb is 2

59、0% 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%

60、Five year survival rate for patients with macroscopic disease is 5%,Malignant 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,

61、 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 germ cell tumor of the ovary is very sensitive to the chemotherapy.

62、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 increas

63、ed from 10% to 90%3.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,P

64、rimary treatment is surgical.Unilateral oophorectomy with preserved reproductive function is considered.PVB and PEB chemotherapy are the treatment of choice for patients with MGCT postoperativelyCourses of chemotherap

65、y 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, although the age of peak incidence fo

66、r 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

67、sex cord stromal tumors.95% of the tumor are unilateral, 95% are confined to the ovary.Unilateral salpingo-oophorectomy seems to appropriate treatment for young patients with stage Ia disease.THBSO is considered s

68、tandard surgery for old patients and advanced stage diseases.,Sex cord stromal tumors,PVB chemotherapy is the treatment of choice for selected patient with sex cord stromal tumor after surgical treatment.Long term foll