先期化疗在晚期上皮性卵巢癌临床治疗中的应用研究
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摘要
卵巢癌在妇科恶性肿瘤中死亡率居首位，目前对于卵巢癌的公认治疗手段是彻底的手术及有效的化疗。通过卵巢癌肿瘤细胞减灭术，最大限度地切除盆腹腔内的肿瘤，为化疗创造条件以提高病人的生存率和生活质量，但临床上多数卵巢癌患者就诊时已经属于晚期，相当部分的患者由于各种因素(如肿瘤广泛盆腹腔转移累及重要的脏器、肿瘤固定、患者状态较差无法耐受手术等)的制约无法达到满意的肿瘤细胞减灭，即使手术由于创伤大、恢复慢，常常影响术后的化疗。卵巢癌对化疗属中度敏感，对铂类药物联合化疗有70-80％的反应率，先期化疗是在术前给予患者有限疗程(1-2疗程)的化疗，使肿瘤减小和松动，改善患者的一般状况为手术治疗创造条件，提高手术的彻底性。
目的：1、对行先期化疗和传统治疗(不作术前化疗)的两组晚期上皮性卵巢癌病人进行对照，回顾性研究，分析不同方法治疗后的结果，探讨先期化疗对于晚期卵巢癌患者手术质量和预后的影响；2、比
解放军总医院军医进修学院硕士学位论文中文摘要
较先期化疗组中PT方案(铂类+泰索蒂(泰素))与PAC方案(铂类+
阿霉素+环磷酞胺)作为一线方案治疗晚期上皮性卵巢癌的术前治疗效
果。
方法:1.回顾性分析22例晚期上皮性卵巢癌妇女，通过l)超声
引导下活检、2)腹腔镜检查取活检、3)腹水查瘤细胞方式获得组织
病理学诊断，辅以先期化疗之后行肿瘤细胞减灭术，与23例传统肿瘤
细胞减灭术后辅以化疗的晚期卵巢癌妇女进行比较。2.先期化疗22
人中PT方案化疗13人与PAC方案化疗9人进行对照。3.对先期化
疗前、后的卵巢癌组织(8例)进行免疫组化(PCN人、Ki一67、bcl一2)
检测。
结果:1、对于盆腹腔广泛转移、估计手术不能达到理想细胞减灭
术目的，手术可能造成较大创伤的晚期卵巢癌病人化疗后行细胞减灭
术病例与直接行细胞减灭术而后化疗病例比较:提高了原发灶及转移
灶的切净程度，减少了术中出血、缩短了手术时间、重症监护日及住
院日(P<0.05);无瘤生存期及总生存期延长，生存曲线有统计学差异
(p<0.0001)。2、PT方案(铂类+泰索蒂(泰素))全程化疗病人与PAC
方案(铂类十阿霉素+环磷酞胺)全程化疗病人比较，PT方案比PAC
方案先期化疗病人的中位肿瘤体积明显缩小，统计学有显著差异
(P<0.05)，利于达到理想的细胞减灭术;两种方案治疗晚期上皮性卵
巢癌，病人的生存率比较无差异。3.PcNA、Ki一67、bcl一2由化疗前
的强阳性表达降低为化疗后的弱阳性或阴性表达。
解放军总医院军医进修学院硕士学位论文中文摘要
结论:l、先期化疗为那些晚期卵巢癌可能达不到理想细胞减灭术
的病人提供手术机会;可明显改善卵巢癌患者肿瘤细胞减灭术的手术
彻底性和手术质量;延长无瘤生存时间、推迟肿瘤复发，延长总生存
时间、提高生存率，进而改善晚期卵巢癌患者的预后和生活质量。2、
PT方案作为晚期卵巢癌病人的一线术前化疗方案较PAC方案使肿瘤
体积缩小明显，但并不延长生存期。3.通过免疫组化检测卵巢癌组织
细胞的增殖与凋亡，为预测病人的预后及制定个体化治疗方案提供临
床依据
The mortality rate of ovarian cancer ranks first in gynecologic malignant cancer. At present , the generally accepted treatment is thorough surgery and operative chemotherapy . By ovarian cancer cytoreductive surgery, the tumor in pelvic and abdominal cavity is resected furthest, creating the condition for chemotherapy to improve the survival rate and life quality of the patients. But, most of the patients with advanced ovarian cancer have been in advanced stage when they went to hospital. A considerable number of patients couldn't achieve satisfactory tumor cytoreductive surgery due to so many factors (eg: tumor offends important organs, tumor is fixed at the bottom of pelvic cavity or the condition of the patient is too bad to endure surgery), and have great trauma and slow recovery. Ovarian cancer is sensitive to a medium degree to chemotherapy, the response rate to platinum-based combination chemotherapy is 70%-80%. Neoadjuvant chemotherapy gives the patients limited course,
improves the general condition, reduces and brises the tumor, creats the condition for surgery and improves the operation exhaustiveness.
Purpose: 1.The aim of this study was to compare the women with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy with those treated with conventionally surgery, to retrospectively study, to analyze the effect of different methods, to discuss the impact of neoadjuvant chemotherapy on the operation quality and prognosis of advanced ovarian cancer patients. 2. It was to compare the effect of PT regime with PAC regime in neoadjuvant chemotherapy group, which were seen as the first-line regime to treat advanced epithelial ovarian cancer.
Methods: 1.To retrospectively analyze and compare 22 patients with advanced epithelial ovarian cancer, who gained the histological and pathologic diagnosis by 1) biopsies under ultrasound guidance; 2) biopsies from laparoscope checking; 3) ascites checking of cancer cell, and were treated with platinum-based combination chemotherapy, i.e. neoadjuvant chemotherapy followed by cytoreductive surgery, with 23 patients in stage III-IV of advanced epithelial ovarian cancer conventionally treated with cytoreductive surgery followed by platinum-based combination chemotherapy. 2. To compare the 13 patients treated with PT regime with the 9 patients with PAC regime
of the 22 patients in neoadjuvant chemotherapy group. 3. To conduct immunohistochemical examination (PCNA, Ki-67, bcl-2) on the advanced ovarian cancer (8 patients) after the treatment of neoadjuvant chemotherapy.
Result: 1. neoadjuvant chemotherapy is the most operative treatment for the patients with advanced ovarian cancer who had extensive pelvic and abdominal metastasis and were assessed that they could not to achieve ideal cytoreductive surgery or their operation would cause great trauma. The patients with advanced ovarian cancer treated with neoadjuvant chemotherapy followed by cytoreductive surgery were compared with those treated with cytoreductive surgery followed by chemotherapy: the resection of primary and metastatic tumor was improved; the blood loss during the operation was reduced: the operative time, the number of postoperative days in the surgical intensive care unit and the number of postoperative hospitalization days were decreased (P<0.05). The progression-free and overall survival days were long, statistical difference was observed in survival curves (P<0.0001). 2. Statistical difference was observed in median tumor volume when the patients with PT (platinum+docetaxel) regime were compared with those with PAC (platinum+adriamycin+cyclophosphamide) regime, the patients
who underwent PT regime had smaller median tumor volume (P<0.05), which helped to achieve ideal cytoreductive surgery; no difference was observed in survival rate in two regimes treating advanced epithelial ovarian cancer. 3. Strong positive reaction of PCNA, Ki-67, bcl-2 before chemotherapy is depressed to weak negative or negative reaction.
Conclusion: 1. neoadjuvant chemotherapy provides the patients with
目的：1、对行先期化疗和传统治疗(不作术前化疗)的两组晚期上皮性卵巢癌病人进行对照，回顾性研究，分析不同方法治疗后的结果，探讨先期化疗对于晚期卵巢癌患者手术质量和预后的影响；2、比
解放军总医院军医进修学院硕士学位论文中文摘要
较先期化疗组中PT方案(铂类+泰索蒂(泰素))与PAC方案(铂类+
阿霉素+环磷酞胺)作为一线方案治疗晚期上皮性卵巢癌的术前治疗效
果。
方法:1.回顾性分析22例晚期上皮性卵巢癌妇女，通过l)超声
引导下活检、2)腹腔镜检查取活检、3)腹水查瘤细胞方式获得组织
病理学诊断，辅以先期化疗之后行肿瘤细胞减灭术，与23例传统肿瘤
细胞减灭术后辅以化疗的晚期卵巢癌妇女进行比较。2.先期化疗22
人中PT方案化疗13人与PAC方案化疗9人进行对照。3.对先期化
疗前、后的卵巢癌组织(8例)进行免疫组化(PCN人、Ki一67、bcl一2)
检测。
结果:1、对于盆腹腔广泛转移、估计手术不能达到理想细胞减灭
术目的，手术可能造成较大创伤的晚期卵巢癌病人化疗后行细胞减灭
术病例与直接行细胞减灭术而后化疗病例比较:提高了原发灶及转移
灶的切净程度，减少了术中出血、缩短了手术时间、重症监护日及住
院日(P<0.05);无瘤生存期及总生存期延长，生存曲线有统计学差异
(p<0.0001)。2、PT方案(铂类+泰索蒂(泰素))全程化疗病人与PAC
方案(铂类十阿霉素+环磷酞胺)全程化疗病人比较，PT方案比PAC
方案先期化疗病人的中位肿瘤体积明显缩小，统计学有显著差异
(P<0.05)，利于达到理想的细胞减灭术;两种方案治疗晚期上皮性卵
巢癌，病人的生存率比较无差异。3.PcNA、Ki一67、bcl一2由化疗前
的强阳性表达降低为化疗后的弱阳性或阴性表达。
解放军总医院军医进修学院硕士学位论文中文摘要
结论:l、先期化疗为那些晚期卵巢癌可能达不到理想细胞减灭术
的病人提供手术机会;可明显改善卵巢癌患者肿瘤细胞减灭术的手术
彻底性和手术质量;延长无瘤生存时间、推迟肿瘤复发，延长总生存
时间、提高生存率，进而改善晚期卵巢癌患者的预后和生活质量。2、
PT方案作为晚期卵巢癌病人的一线术前化疗方案较PAC方案使肿瘤
体积缩小明显，但并不延长生存期。3.通过免疫组化检测卵巢癌组织
细胞的增殖与凋亡，为预测病人的预后及制定个体化治疗方案提供临
床依据
The mortality rate of ovarian cancer ranks first in gynecologic malignant cancer. At present , the generally accepted treatment is thorough surgery and operative chemotherapy . By ovarian cancer cytoreductive surgery, the tumor in pelvic and abdominal cavity is resected furthest, creating the condition for chemotherapy to improve the survival rate and life quality of the patients. But, most of the patients with advanced ovarian cancer have been in advanced stage when they went to hospital. A considerable number of patients couldn't achieve satisfactory tumor cytoreductive surgery due to so many factors (eg: tumor offends important organs, tumor is fixed at the bottom of pelvic cavity or the condition of the patient is too bad to endure surgery), and have great trauma and slow recovery. Ovarian cancer is sensitive to a medium degree to chemotherapy, the response rate to platinum-based combination chemotherapy is 70%-80%. Neoadjuvant chemotherapy gives the patients limited course,
improves the general condition, reduces and brises the tumor, creats the condition for surgery and improves the operation exhaustiveness.
Purpose: 1.The aim of this study was to compare the women with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy with those treated with conventionally surgery, to retrospectively study, to analyze the effect of different methods, to discuss the impact of neoadjuvant chemotherapy on the operation quality and prognosis of advanced ovarian cancer patients. 2. It was to compare the effect of PT regime with PAC regime in neoadjuvant chemotherapy group, which were seen as the first-line regime to treat advanced epithelial ovarian cancer.
Methods: 1.To retrospectively analyze and compare 22 patients with advanced epithelial ovarian cancer, who gained the histological and pathologic diagnosis by 1) biopsies under ultrasound guidance; 2) biopsies from laparoscope checking; 3) ascites checking of cancer cell, and were treated with platinum-based combination chemotherapy, i.e. neoadjuvant chemotherapy followed by cytoreductive surgery, with 23 patients in stage III-IV of advanced epithelial ovarian cancer conventionally treated with cytoreductive surgery followed by platinum-based combination chemotherapy. 2. To compare the 13 patients treated with PT regime with the 9 patients with PAC regime
of the 22 patients in neoadjuvant chemotherapy group. 3. To conduct immunohistochemical examination (PCNA, Ki-67, bcl-2) on the advanced ovarian cancer (8 patients) after the treatment of neoadjuvant chemotherapy.
Result: 1. neoadjuvant chemotherapy is the most operative treatment for the patients with advanced ovarian cancer who had extensive pelvic and abdominal metastasis and were assessed that they could not to achieve ideal cytoreductive surgery or their operation would cause great trauma. The patients with advanced ovarian cancer treated with neoadjuvant chemotherapy followed by cytoreductive surgery were compared with those treated with cytoreductive surgery followed by chemotherapy: the resection of primary and metastatic tumor was improved; the blood loss during the operation was reduced: the operative time, the number of postoperative days in the surgical intensive care unit and the number of postoperative hospitalization days were decreased (P<0.05). The progression-free and overall survival days were long, statistical difference was observed in survival curves (P<0.0001). 2. Statistical difference was observed in median tumor volume when the patients with PT (platinum+docetaxel) regime were compared with those with PAC (platinum+adriamycin+cyclophosphamide) regime, the patients
who underwent PT regime had smaller median tumor volume (P<0.05), which helped to achieve ideal cytoreductive surgery; no difference was observed in survival rate in two regimes treating advanced epithelial ovarian cancer. 3. Strong positive reaction of PCNA, Ki-67, bcl-2 before chemotherapy is depressed to weak negative or negative reaction.
Conclusion: 1. neoadjuvant chemotherapy provides the patients with
引文
1. Jacob JH, Gershenson DM, Morris, et al. Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian dancer. Gynecol Oncol, 1991, 42:146-151
2. Hoskins WJ. Surgical staging and cytoreduetive surgery of epithelial ovarian cancer. Cancer. 1993, 71 : 1534-1540
3. Schwartz PE. Surgical management of ovarian cancer .Arch Surg, 1981, 16:99-106
4. Cannistra SA. Cancer of the ovary. N Engl J Med 1993;329:1550-1559
5. Chambers JK; Chambers SK, Voynick IM, et al. Neoadjuvant chemotherapy in Stage Ⅹ ovarian carcinoma. Gynecol Oncol, 1990, 37:327-331
6. Schwartz PZ; Chambers JT, Makuch R. Neoadjuvant chemotherapy for advanced ovarian cancer. Gynecol Oncol. 1994; 53:33-37
7. Schwartz,-P-E. Neoadjuvant chemotherapy for the management of ovarian cancer. Best-Pract-Res-Clin-Obstet-Gynaecol, 2002, 16(4): 585-96
8. Nelson B, Rosenfeld AT, Schwartz PE; Preoperative abdominopelvic computed tomographic prediction of optimal cytoreduction in epithelial ovarian carcinoma. J Clin Oncol, 1993,
11:166-172
9. Huober J; Meyer A; Wagner U. The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer. J Cancer Res Clin Oncol, 2002, 128(3): 153-60
10. Kayikcioglu F; Kose MF; Boran N ; et al. Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma. Int J Gynecol Cancer, 2001, 11(6): 466-70
11. Eisenkop SM; Spirtos NM; What are the current surgical objectives, strategies, and technical capabilities of gynecologic oncologists treating advanced epithelial ovarian cancer? Gynecol Oncol. 2001;82(3): 489-497
12. Favalli G; Odicino F; Pecorelli S. Surgery of advanced malignant epithelial tumours of the ovary.Forum-(Genova),2000,10(4): 3123-3120
13. Kuhn W, Rutke S, Spathe K , et al .Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrice Stage ⅢCovarian carcinoma. Cancer, 2001, 92: 2585-2591.
14. Hatae M; Onishi Y; Nakamura T; et al. The role of surgery for advanced epithelial ovarian cancer. Gan To Kagaku Ryoho, 1998,
25(2): 201-207
15. Jacob JH, Gershenson DM, Mrris M, et al. Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer. Gynecol Oncol, 1991, 42:146-151
16. Eisenkop SM; Spirtos NM; Friedman RL. Neoadjuvant chemotherapy for advanced ovarian cancer. Gynecol Oncol, 1999, 74(2): 311-312
17. Ushijima K; Ota S; Komai K et al. Clinical assessment of neoadjuvant chemotherapy and interval cytoreductive surgery for unresectable advanced ovarian cancer. Int-Surg, 2002, 87(3): 185-90
18. Bruchim I; Altaras M; Fishman A. Age contrasts in clinical characteristics and pattern of care in patients with epithelial ovarian cancer. Gynecol-Oncol, 2002,86(3): 274-278
19. Pecorelli S; Odicino F; Favalli G; et al. Interval debulking surgery in advanced epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol, 2002, 16(4): 573-83
20. Covens AL. A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol, 2000, 78(3 Pt 1): 269-274
21. Chan YM; Ng TY; Ngan HY. Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a
prospective longitudinal study. Gynecol-Oncol, 2003,88(1): 9-16
22. Zang R; Zhang Z; Cai S. Factors affecting disease recurrence and the role of secondary therapies in the management for patients with recurrent ovarian carcinoma. Zhonghua-Fu-Chan-Ke-Za-Zhi, 2002, 37(9): 546-9
23. Feng Y; Sun T. Short-term effects of chemotherapy-surgery -chemotherapy regimen on clinically inoperable advanced ovarian cancer. Chin Med J (Engl), 1998,111(8): 722-725
24. Onnis A; Marchetti M; Padovan P; et al. Neoadjuvant chemotherapy in advanced ovarian cancer. Eur-J-Gynaecol-Oncol, 1996, 17(5): 393-396
25. Hatae M; Onishi Y; Nakamura T; et al. Neoadjuvant chemotherapy for advanced epithelial ovarian cancer. Gan To Kagaku Ryoho, 2001, 28(12): 1833-1837
26. Vergote IB; De Wever I; Decloedt J; et al. Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer. Semin Oncol, 2000,27(3 Suppl 7): 31-36
27. Brow DC, Gatter KC, et al. Monoclonal antibody Ki-67: its us in histopathology. 1990; 17:489-503
28. Ramal M, Jacobs W, et al. Proliferation in malignant mesothelioma as determined by mitosis counts and immunoreactivity for
proliferating cell nuclear anclear antigen. J Pathhol, 1994, 172:247-253
29. Broaddus V, et al. Asbestos the mesothelial cell and malignancy:a matter of life or death. Am J Respir. Cell Mol Biol, 1997, 17:657-659
2. Hoskins WJ. Surgical staging and cytoreduetive surgery of epithelial ovarian cancer. Cancer. 1993, 71 : 1534-1540
3. Schwartz PE. Surgical management of ovarian cancer .Arch Surg, 1981, 16:99-106
4. Cannistra SA. Cancer of the ovary. N Engl J Med 1993;329:1550-1559
5. Chambers JK; Chambers SK, Voynick IM, et al. Neoadjuvant chemotherapy in Stage Ⅹ ovarian carcinoma. Gynecol Oncol, 1990, 37:327-331
6. Schwartz PZ; Chambers JT, Makuch R. Neoadjuvant chemotherapy for advanced ovarian cancer. Gynecol Oncol. 1994; 53:33-37
7. Schwartz,-P-E. Neoadjuvant chemotherapy for the management of ovarian cancer. Best-Pract-Res-Clin-Obstet-Gynaecol, 2002, 16(4): 585-96
8. Nelson B, Rosenfeld AT, Schwartz PE; Preoperative abdominopelvic computed tomographic prediction of optimal cytoreduction in epithelial ovarian carcinoma. J Clin Oncol, 1993,
11:166-172
9. Huober J; Meyer A; Wagner U. The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer. J Cancer Res Clin Oncol, 2002, 128(3): 153-60
10. Kayikcioglu F; Kose MF; Boran N ; et al. Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma. Int J Gynecol Cancer, 2001, 11(6): 466-70
11. Eisenkop SM; Spirtos NM; What are the current surgical objectives, strategies, and technical capabilities of gynecologic oncologists treating advanced epithelial ovarian cancer? Gynecol Oncol. 2001;82(3): 489-497
12. Favalli G; Odicino F; Pecorelli S. Surgery of advanced malignant epithelial tumours of the ovary.Forum-(Genova),2000,10(4): 3123-3120
13. Kuhn W, Rutke S, Spathe K , et al .Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrice Stage ⅢCovarian carcinoma. Cancer, 2001, 92: 2585-2591.
14. Hatae M; Onishi Y; Nakamura T; et al. The role of surgery for advanced epithelial ovarian cancer. Gan To Kagaku Ryoho, 1998,
25(2): 201-207
15. Jacob JH, Gershenson DM, Mrris M, et al. Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer. Gynecol Oncol, 1991, 42:146-151
16. Eisenkop SM; Spirtos NM; Friedman RL. Neoadjuvant chemotherapy for advanced ovarian cancer. Gynecol Oncol, 1999, 74(2): 311-312
17. Ushijima K; Ota S; Komai K et al. Clinical assessment of neoadjuvant chemotherapy and interval cytoreductive surgery for unresectable advanced ovarian cancer. Int-Surg, 2002, 87(3): 185-90
18. Bruchim I; Altaras M; Fishman A. Age contrasts in clinical characteristics and pattern of care in patients with epithelial ovarian cancer. Gynecol-Oncol, 2002,86(3): 274-278
19. Pecorelli S; Odicino F; Favalli G; et al. Interval debulking surgery in advanced epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol, 2002, 16(4): 573-83
20. Covens AL. A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol, 2000, 78(3 Pt 1): 269-274
21. Chan YM; Ng TY; Ngan HY. Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a
prospective longitudinal study. Gynecol-Oncol, 2003,88(1): 9-16
22. Zang R; Zhang Z; Cai S. Factors affecting disease recurrence and the role of secondary therapies in the management for patients with recurrent ovarian carcinoma. Zhonghua-Fu-Chan-Ke-Za-Zhi, 2002, 37(9): 546-9
23. Feng Y; Sun T. Short-term effects of chemotherapy-surgery -chemotherapy regimen on clinically inoperable advanced ovarian cancer. Chin Med J (Engl), 1998,111(8): 722-725
24. Onnis A; Marchetti M; Padovan P; et al. Neoadjuvant chemotherapy in advanced ovarian cancer. Eur-J-Gynaecol-Oncol, 1996, 17(5): 393-396
25. Hatae M; Onishi Y; Nakamura T; et al. Neoadjuvant chemotherapy for advanced epithelial ovarian cancer. Gan To Kagaku Ryoho, 2001, 28(12): 1833-1837
26. Vergote IB; De Wever I; Decloedt J; et al. Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer. Semin Oncol, 2000,27(3 Suppl 7): 31-36
27. Brow DC, Gatter KC, et al. Monoclonal antibody Ki-67: its us in histopathology. 1990; 17:489-503
28. Ramal M, Jacobs W, et al. Proliferation in malignant mesothelioma as determined by mitosis counts and immunoreactivity for
proliferating cell nuclear anclear antigen. J Pathhol, 1994, 172:247-253
29. Broaddus V, et al. Asbestos the mesothelial cell and malignancy:a matter of life or death. Am J Respir. Cell Mol Biol, 1997, 17:657-659