晚期上皮性卵巢癌患者“间歇性肿瘤细胞减灭术”手术适应证的探讨

目的:探讨间歇性肿瘤细胞减灭术(IDS)的适应证。方法:采用回顾性病例对照研究,分析2000年1月至2009年12月间71例初次肿瘤细胞减灭术不满意的ⅢC～Ⅳ期卵巢上皮癌(包括原发性腹膜癌,原发性输卵管癌)患者的资料。A组(n=41)初次减灭术后单纯化疗6～8疗程;B组(n=30)经3～4个疗程化疗后行间歇性肿瘤细胞减灭术,然后继续化疗4～6疗程。化疗方案均为铂类为基础的联合化疗。两组患者的化疗方案和疗程无差异。通过比较两组患者的临床特征、手术及生存情况,以及B组患者IDS术前CA125、B超检查与术后病理结果的对应关系,总结IDS的适应证。结果:B组30例患者中23例(76.7%)最终达到满意减瘤,共有11例术后病理结果为阴性,术前CA125或B超对病理结果阳性预测的敏感度差,CA125的特异性达100%。CA125联合B超的预测准确率为70%。A、B组的五年生存率(P=0.790)、OS(P=0.254)和PFS(P=0.289)均无显著性差异。B组中无肉眼残留病灶患者的PFS和OS较A组有明显延长的趋势。结论:间歇性肿瘤细胞减灭术主要适应证是:初次肿瘤细胞减灭术采用"基本术式",3个疗程化疗后部分缓解,CA125仍异常;或CA125恢复正常,最好经PET-CT或增强CT明确有残留病灶。残留病灶有可能通过再次手术切除干净,达到无肉眼残留,这部分患者有可能生存获益。     

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery

Objective

To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery.

Methods

Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated.

Results

The 124 enrolled patients had a median age of 62 years (range, 35–79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR] = 1.94, p = 0.003), residual cancer at the end of surgery ≥ 1 cm (HR = 3.78, p < 0.001), and histological grade 0–1 (HR = 1.65, p = 0.03) were independent predictors of decreased OS. Grade 0–1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio = 8.42, p = 0.003).

Conclusions

Residual disease of ≥ 1 cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.     

Drug sensitivity-related benefit of systematic lymphadenectomy during cytoreductive surgery in optimally debulked stages IIIc and IV ovarian cancer

OBJECTIVE: The purpose of this study is to assess the survival experience following systematic lymphadenectomy (LNX) in conjunction with primary but optimal cytoreductive surgery in advanced epithelial ovarian cancer (OC) patients when followed by intensive chemotherapy. METHODS: This is a retrospective analysis of all women with OC who were treated in our institution between 1992 and 2000. A total of 98 patients with stages IIIc-IV of OC underwent primary cytoreductive surgery which was 'optimal' (<1 cm residual disease). All patients subsequently received postoperative platinum-containing chemotherapy. Group I, consisting of 51 patients underwent LNX; Group II, consisting of 47 patients did not undergo LNX. The percentage of patients failing to respond to chemotherapy in each group was similar. Each group had statistically equivalent age, stage, regimens of chemotherapy performed, and all other known prognostic factors. RESULTS: No survival benefit could be seen in platinum-sensitive patients. However, in patients who failed to respond to chemotherapy, the 2-year progression-free survival (PFS) (42.8% vs. 14.3%) and overall survival (OS) (51.2% vs. 28.8%) was quite different. LNX significantly improved those of drug-resistant patients when optimal cytoreductive surgery was performed [P = 0.008, risk ratio (rr) = 2.675, 95% confidence interval (CI) = 1.251-5.724]. Cox's proportional analysis shows that LNX was one of the three most significant covariate with the tumor grade and the number of postoperative residual lesions. CONCLUSIONS: The results show that LNX might be of benefit in patients who have optimal primary cytoreductive surgery and who do not respond to platinum-based chemotherapy.     

Outcome of patients with advanced ovarian cancer who do not undergo debulking surgery: A single institution retrospective review

Objective

To assess the outcome of patients with advanced ovarian cancer (OC) who were treated without surgery, having received upfront chemotherapy and no interval debulking surgery (IDS).

Chemotherapy delay after primary debulking surgery for ovarian cancer

Objective

To determine the association of chemotherapy delay with overall survival (OS) and investigate predictors of delay among a population-representative American ovarian cancer cohort.

Prognostic significance of DNA index in advanced ovarian cancer

Abstract. Flow cytometric analysis of single cell DNA content was performed in 99 malignant ovarian tumors FIGO stages III and IV. The tumors were divided into two groups with DNA index 1.5 and > 1.5, respectively. The tumor DNA index correlated with histopathological differentiation, frequency of complete pathological remission, and prognosis.     

Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer

Objective

The purpose of this study was to evaluate the prognostic significance of serum human epididymis protein 4 (HE4) level in patients with epithelial ovarian cancer.

Study design

A total of 78 women diagnosed with a pelvic mass and operated on in our institute comprised our cohort. Forty-five of these were diagnosed with epithelial ovarian cancer and treated with debulking surgery, followed by taxane and platinum-based chemotherapy as clinically indicated. Preoperatively obtained serum samples were analyzed for levels of HE4 and CA125.

Results

The elevated serum HE4 level was related to advanced stage and serous type of cancer. The median duration of the follow-up was 35.1 months. In advanced stage, the median progression-free survival (PFS) of patients with elevated serum HE4 levels was 20.1 months (95% CI, 15.7–24.6 months), whereas that of patients with normal serum HE4 level was 24.2 months (95% CI, 13.9–34.6 months) (p = 0.029). Independent predictors for PFS in patients with advanced stage EOC included serum HE4 level (hazard ratio 2.24; 95% CI, 1.14 to 6.84; p = 0.048).

Conclusions

Our results demonstrated that an elevated serum HE4 level was related to the advanced stage of epithelial ovarian cancer. An elevated serum level of HE4 is a poor prognostic factor for PFS in patients with epithelial ovarian cancer who were treated with debulking surgery and adjuvant taxane and platinum-based chemotherapy. The serum HE4 level is a promising indicator for the progression of cancer as well as a biomarker for the detection of epithelial ovarian cancer.     

Prognostic factors in advanced ovarian cancer

In this review, different factors with suspected effect on survival of patients with advanced ovarian cancer are analysed. The volume of residual disease after surgical debulking is one of the most important factors predicting outcome. However, the extent of cytoreduction may not be the only 'responsible' factor indicating a better prognosis; the underlying biology of those debulkable tumors may also play a role in defining the more favorable outcome. Seven reports have studied different prognostic factors by multivariate analysis: performance status, stage, age, grade, histology, tumor size, residual tumor, type of chemotherapy given, and ploidy status are the most common analysed parameters. A meta-analysis indicated that treatment with cisplatin and disease stage are the only independent prognostic variables. Some investigators have developed prognostic indexes with good predictive power, incorporating objective prognostic variables. This approach may be more useful than applying individual factors to each patient. The absolute titer of carbohydrate antigen 125, its decline after several courses of chemotherapy, or its half-life have been correlated with prognosis in some instances, but low sensitivity may be a problem. Other biologic factors with some prognostic potential in ovarian cancer are the expression of lung-resistance protein and the over-expression of c-erbB-2, both perhaps related to resistance to chemotherapy, the product of the metastasis suppressor gene nm23, the epidermal growth factor receptor, heat shock proteins (HSP-60), and plasma or ascites levels of macrophage colony-stimulating factor. Most of these predictors were explored in selected and often small series of patients, and their roles should be confirmed in well-designed confirmatory trials.     

Impact of operative start time on surgical outcomes in patients undergoing primary cytoreduction for advanced ovarian cancer

Objectives

To evaluate the impact of operative start time (OST) on surgical outcomes in patients with advanced ovarian cancer.

Methods

All stage IIIB-IV serous ovarian cancer patients who underwent primary surgery at our institution from 1/01 to 1/10 were identified. Fourteen factors were evaluated for an association with surgical outcomes including OST and OR tumor index (1 point each for carcinomatosis and/or bulky [≥ 1 cm] upper abdominal disease). Univariate logistic regression considering within-surgeon clustering was performed for cytoreduction to ≤ 1 cm versus > 1 cm residual disease. In patients with ≤ 1 cm residual disease, univariate logistic regression considering within-surgeon clustering was performed for 1-10 mm residual disease versus complete gross resection (CGR, 0 mm residual). A multivariate logistic model was developed based on univariate analysis results in the ≤ 1 cm residual disease cohort.

Results

Of 422 patients, residual disease was: 0 mm, 144 (34.1%); 1-10 mm, 175 (41.5%); > 10 mm, 103 (23.3%). OST was not associated with cytoreduction to ≤ 1 cm residual disease on univariate analysis. In the ≤ 1 cm residual disease cohort, albumin, CA-125, ascites, ASA score, stage, OR tumor index, and OST were associated with CGR on univariate analysis. Earlier OSTs were associated with increased rates of CGR. On multivariate analysis, CA-125 was independently associated with CGR. OST was associated with CGR in patients with an OR tumor index of 2 but not an OR tumor index < 2.

Conclusions

OST was not associated with cytoreduction to ≤ 1 cm residual disease in patients with advanced serous ovarian cancer. In the cohort of patients with ≤ 1 cm residual disease, later OSTs were associated with reduced rates of CGR in patients with greater tumor burden.     

Quality of life in patients with endometrial cancer treated with or without systematic lymphadenectomy

Objective

To compare the quality of life (QoL) of women affected by endometrial cancer treated with surgery with or without systematic lymphadenectomy.

Study design

Consecutive patients affected by stages I and II endometrial cancer and treated with surgery between 2008 and 2011 were selected. Eligible subjects were divided into two groups: Group A consisted of 36 patients who had hysterectomy plus bilateral salpingo-oophorectomy without lymphadenectomy; Group B consisted of 40 patients who had hysterectomy plus salpingo-oophorectomy plus pelvic and aortic lymphadenectomy. The EORTC Quality of Life Questionnaire-Cancer Module (QLQ-C30) and Quality of Life Questionnaire-Endometrial Cancer Module (QLQ-EN24) were administered to selected patients. All data were recorded and then analyzed using the scoring manual of the EORTC Quality of Life Group.

Results

Among symptom scales, only lymphedema gave a statistically significant difference among two groups, with a score of 10.64 ± 17.43 in Group A and 21.66 ± 24.51 in Group B (p = 0.0285). The p value obtained comparing the “Global Health Status” (items 29 and 30) in Group A and in Group B was not statistically significant.

Conclusion

Lymphadenectomy did not influence negatively global health status, but lymphadenectomy maintained its importance in determining a patient's prognosis and in tailoring adjuvant therapies. We therefore support its practice as part of the surgical procedure in patients affected by high risk endometrial cancer.     

Tamoxifen in patients with advanced epithelial ovarian cancer

Tamoxifen was administered to 30 patients with persistent or recurrent epithelial ovarian cancer following initial plantinum-based chemotherapy. Two complete remissions (lasting 41 months and 12 months, respectively) were documented (6.6%), while 10 patients (33.3%) had stabilization of disease for a mean duration of 11.5 months. Tamoxifen was not associated with any significant toxicity and is a reasonable therapeutic option for patients with persistent or recurrent ovarian cancer, although it is only associated with modest activity. This paper reviews our experience with tamoxifen and summarizes the world literature.     

Intraoperative hypothermia during primary surgical cytoreduction for advanced ovarian cancer: Risk factors and associations with postoperative morbidity

Objective

The objective of this study was to evaluate the risk factors and potential morbidity associated with intraoperative hypothermia (IH) during cytoreductive surgery (CRS) for advanced ovarian cancer.

Methods

Demographic and perioperative data were collected for all patients with stage IIIC–IV ovarian, fallopian tube, and primary peritoneal carcinoma who underwent primary CRS at our institution from 2001 to 2010. Only patients with carcinomatosis and/or bulky upper abdominal disease and residual disease of < 1 cm were included. Intraoperative hypothermia was defined as temperature of < 36.0 degrees Celsius (°C). Associations with 21 perioperative factors, 12 systems-based complications, and specific complications including but not limited to venous thromboembolism and surgical site infection were evaluated.

Results

Two hundred ninety-seven patients met the inclusion criteria. An intraoperative temperature < 36 °C was noted in 72.1% of patients, and a temperature < 36 °C at the time of abdominal closure was noted in 45.5%. Intraoperative vasopressors (P = 0.02), epidural anesthesia (P = 0.01), transfusion of fresh frozen plasma (P < 0.05), and blood loss (P = 0.01) were associated with IH. There was no association between IH and postoperative complications in general (P = 0.48) or specifically grade 3–5 complications (P = 0.34). Univariate analysis did show an association between hematologic complications and IH; however, this did not persist on multivariate analysis (P = 0.14).

Conclusions

In patients who underwent optimal primary CRS for advanced ovarian cancer, IH alone was not associated with the development of postoperative complications. Postoperative morbidity in these patients is multifactorial and further investigation into modifiable risk factors is warranted.     

Role of hysterectomy and lymphadenectomy in the management of early-stage borderline ovarian tumors

Objective

To examine survival of women with stage T1 borderline ovarian tumors (BOTs) stratified by hysterectomy and lymphadenectomy status at surgery.

Early ovarian cancer: Is there a role for systematic pelvic and para-aortic lymphadenectomy?

Baiocchi G, Raspagliesi F, Grosso G, Fontanelli R, Cobellis L, di Re E, di Re F. Early ovarian cancer: Is there a role for systematic pelvis and para-aortic lymphadenectomy? Int J Gynecol Cancer 1998; 8 : 103–108.
In order to focus on the incidence and the clinical significance of lymphatic spread in patients with cancer apparently confined to the ovaries, we present our 20 year experience in a large series of patients with early ovarian cancer who had systematic pelvic and para-aortic lymphadenectomy. A retrospective study of 280 consecutive patients is presented. Systematic pelvic and para-aortic lymphadenectomy was performed in 205 cases (73.2%). Selective sampling and node biopsy were performed in 30 (10.7%) and 7 (2.5%), respectively. Node metastases were found in 32/242 patients (13.2%). The incidence of metastatic nodes was significantly higher in patients with serous adenocarcinomas and/or poorly-differentiated tumors. When few nodes were involved (1–3) lymphatic spread was most ipsilateral to the tumor. Even though the retrospective nature of the study has to be considered, univariate analysis revealed statistically significant differences in 5-year survival based on FIGO stage, histology, grade of differentiation, and node status. By contrast, using multivariate analysis, none of these risk factors was an independent variable for predicting long-term survival. However, node status closely approached the statistically significant level ( P = 0.06). Only prospective and randomized studies can clarify the role of lymphadenectomy in early ovarian cancer. However, while awaiting these results, this surgical procedure should be a part of a research protocol.     

The impact of video-assisted thoracic surgery (VATS) in patients with suspected advanced ovarian malignancies and pleural effusions

OBJECTIVES: We previously reported our initial experience of patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent video-assessed thoracic surgery (VATS) before planned abdominal exploration. The objective of this study was to report the surgical findings and management of patients who underwent VATS in an update of our experience. METHODS: We performed a retrospective review of all patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS for assessment of extent of intrathoracic disease at our institution between 6/01 and 8/05. RESULTS: Twenty-three patients with a median age of 61 years (range, 36-79) were identified. VATS was performed for right-sided effusions in 17 patients (74%), and a median of 1350 ml (400-3700 ml) of pleural fluid was drained. VATS demonstrated macroscopic disease in 15 (65%) patients, with nodules >1 cm in 11/15 (73%), and nodules <1 cm in 4/15 (27%). Macroscopic intrathoracic disease was found in 4/10 (40%) patients with negative cytology. Intrathoracic cytoreduction was performed in 3/11 patients (27%) with intrathoracic disease >1 cm. After VATS, 12/23 patients (52%) underwent primary surgical management, with cytoreduction to < or =1 cm achieved in 11/12 patients (92%). The other eleven patients received primary chemotherapy after undergoing diagnostic laparoscopy alone (4/11) or no further abdominal exploration (7/11). Nine of these patients proceeded to interval cytoreduction, while 2 had pathology demonstrating upper gastrointestinal and lymphoma primaries at the time of VATS. Final diagnosis of primary site of disease included: ovary, 14 (61%); endometrial, 2 (9%); dual ovarian/endometrial primaries, 1 (4%); fallopian tube, 1 (4%); primary peritoneal, 1 (4%); other, 4 (17%). Overall, findings at VATS altered primary surgical management in 11/23 (48%) patients. CONCLUSIONS: Sixty-five percent of patients with suspected advanced ovarian cancer and moderate to large pleural effusions had gross intrathoracic disease identified at VATS, with the majority (11/15, 73%) having disease >1 cm in diameter. Use of VATS allows for assessment of intrathoracic disease and may help identify candidates for primary cytoreductive surgery and possible intrathoracic cytoreduction versus neoadjuvant chemotherapy.     

GnRH analogues as an adjuvant therapy for ovarian cancer patients.

OBJECTIVES: Lowering gonadotropin levels with gonadotropin-releasing hormone (GnRH) analogues in patients with ovarian cancer remains open to debate. The aim of this study was to assess the results of treatment in stage III and stage IV ovarian cancer patients who had surgery supplemented with chemotherapy, radiotherapy, and GnRH analogues. Gonadotropin levels were monitored during treatment. METHODS: The study group comprised 69 patients aged 27-70 years, stratified according to the type of treatment. The overall disease-free, 5-year survival rates and the frequency of remissions were analyzed. Hormonal tests [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were performed in 58 patients. Associations were checked between gonadotropin levels, clinical findings, and survival. The results were statistically compared. RESULTS: Statistically significant differences were noted when chemotherapy was supplemented with GnRH analogues and/or radiotherapy. Administration of GnRH analogues resulted in significantly lower levels of LH than of FSH. Levels of FSH were significantly lower in patients surviving at least 5 years or in complete remission at the time of this study. CONCLUSIONS: Combined therapy can produce favorable results in late-stage ovarian cancer, and GnRH analogues have an important role in treatment strategy.     

Intestinal obstruction in patients with advanced ovarian cancer

A retrospective analysis of the management of intestinal obstruction in 31 patients with advanced ovarian carcinoma is described. Between 1981 and 1992 31 patients developed intestinal obstruction after their initial treatment. Nineteen patients underwent surgery, while the remaining 12 were treated conservatively. Careful evaluation with contrast studies of both the small intestine and colon is recommended to improve the prediction of site(s) of obstruction, and may reduce the number of unsuccessful operative procedures. Fifteen of the surgically treated patients survived for a period of 60 days or more. The majority, 13, were discharged to their homes after an average hospital stay of 24 days. Major postoperative complications occurred in three of the 19 patients. There was no surgical-related mortality. Two patients died within 30 days postoperatively (urosepsis and advanced tumor). While the median survival in the 19 surgical treated patients was 109 days (range 15–775), the conservatively treated 12 patients survived for a mean of 37 days (range 6–260). Surgical management of intestinal obstruction in selected cases is feasible and improves quality of life substantially.