Prognostic significance of lymph node metastasis and lymphadenectomy in early-stage ovarian carcinosarcoma.

BACKGROUND: The role that lymph node dissection (LND) plays in the management of ovarian carcinosarcoma (OCS) is unclear due to its rarity. This study investigated lymph node metastasis (LNM) prevalence in women with early OCS and effects of LND and LNM on survival. METHODS: Data of women diagnosed with OCS, whose primary tumor was confined to ovaries (American Joint Committee on Cancer [AJCC] T1) or pelvic cavity (AJCC T2), between 1988 and 2010 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified into lymphadenectomy (LND [+]) and no lymphadenectomy (LND [-]) groups. RESULTS: A total of 363 women were included. The prevalence of LNM was 9.6% in AJCC T1 and 16.3% in AJCC T2. Multivariate analysis showed that LND and AJCC T categories were independent prognostic variables, irrespective of cancer-specific survival (CSS) or overall survival (OS). Subgroup analysis by AJCC T categories revealed that LND (+) group in AJCC T2 had a better survival outcome compared to LND (-) group (CSS, HR [95% CI] = 0.61 [0.43-0.87]; OS, HR [95% CI] = 0.59 [0.42-0.83]). There was no survival difference between groups in AJCC T1 (CSS, HR [95% CI] = 0.96 [0.56-1.65]; OS, HR [95% CI] = 0.88 [0.56-1.38]). Multivariate analysis was further carried out in LND (+) group and demonstrated that LNM and AJCC T2 had poor CSS and OS. Subgroup analysis by AJCC T categories showed that worse survival was observed in LNM (+) group compared to LNM (-) group in AJCC T2 (CSS, HR [95% CI] = 3.62 [1.50-8.73]; OS, HR [95% CI] = 3.71 [1.59-8.68]) but not in AJCC T1 (CSS, HR [95% CI] = 1.78 [0.50-6.37]; OS, HR [95% CI] = 1.97 [0.61-6.39]). CONCLUSION: Regional lymphadenectomy should be performed in patients with AJCC T2 OCS. LND and LNM were not significantly associated with prognosis in AJCC T1 while LNM had a trend toward worse survival.

Nedaplatin and paclitaxel compared with carboplatin and paclitaxel for patients with platinum-sensitive recurrent ovarian cancer.

This retrospective cohort study was designed to evaluate the efficacy and safety of nedaplatin plus paclitaxel (NP) compared with carboplatin plus paclitaxel (CP) in platinum-sensitive recurrent ovarian cancer. Patients with histologically proven epithelial ovarian cancer with recurrent interval ≥6 months after finishing platinum-based therapies between January 1, 2009 and December 31, 2014 were investigated. Patients received an intravenous infusion of NP (nedaplatin 80 mg/m2 plus paclitaxel 175 mg/m2) or CP (carboplatin at an area under the curve of 5 plus paclitaxel 175 mg/m2) protocols every 3 weeks for at least 6-8 cycles or until disease progression. Primary end point was progression-free survival (PFS); secondary end points were toxicity and overall survival (OS). 436 patients were included in the study, containing 241 cases receiving CP regimen and 195 cases receiving NP regimen, who were all contained in safety analysis. Because of 61 patients with unbearable toxicity and poor compliance, 375 patients were finally included in the efficacy analysis. With median follow-up of 63.5 months, PFS was 11.0 months with NP regimen versus 9.5 months with CP regimen (P=0.109). Subgroup analysis indicated that PFS of the NP arm was statistically superior to the CP arm when recurrent interval was 6-12 months (P=0.048); median PFS was 10.0 versus 8.0 months, respectively. There was no significant difference in overall survival between two groups. More frequent grade 3-4 neutropenia (13.3% vs 33.6%), thrombocytopenia (5.6% vs 14.5%) and hypersensitivity reactions (5.6% vs 21.9% ) were observed in CP arm (P<0.01). Compared to the CP, NP regimen did not improve 5-year overall survival in platinum-sensitive recurrent ovarian cancer, but it had better tolerance. NP obtained significant benefit in progression-free survival when the recurrent interval was between 6 and 12 months, although the efficacy of two regimens were similar when the recurrent interval ≥12 months.

Copy number changes of 4-gene set may predict early relapse in advanced epithelial ovarian cancer after initial platinum-paclitaxel chemotherapy.

For advanced epithelial ovarian cancer (EOC), time to recurrence (TTR) is an important indicator to gauge the therapeutic efficacy of postoperative adjuvant chemotherapy. Our objective was to determine the genes that could potentially distinguish patients with short versus long TTR after initial administration of platinum-paclitaxel combination chemotherapy in advanced EOC. Tumor samples of 159 patients were obtained during the primary cytoreduction. Array comparative genomic hybridization (CGH) was carried with genomic DNA from 17 EOC samples (8 with TTR > 15 months and 9 with TTR ≤ 6 months) to screen candidate gene set, copy-number changes (CNC) of which were significantly different between early and late relapse cases. Seventeen candidate genes were identified by array CGH. The analysis of consistency between real-time PCR and array CGH revealed that 4 genes displayed consistent results, namely GSTT1, ISG20L1, STARD5 and FREM1. In a 142-case validation set, CNC of 4 candidate genes was evaluated and verified by real-time PCR. Sixty five point five percent of the patients were correctly divided into early (TTR ≤ 10 months) and late (TTR > 10 months) recurrent group by CNC of the 4 genes using discriminant analysis. The results showed that CNC of 4-gene set could potentially determine early (TTR ≤ 10 months) or late relapse (TTR > 10 months) after initial platinum-paclitaxel combination chemotherapy in advanced EOC.

[A prospective study of adenosine triphosphate-tumor chemosensitivity assay directed chemotherapy in patients with recurrent ovarian cancer].

OBJECTIVE: To investigate the efficacy of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer. METHODS: From August 2010 to June 2012, recurrent epithelial ovarian cancer patients were prospectively enrollmented in Cancer Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The entry criteria are as follows: (1) Histologically proven to be epithelial ovarian cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status > 60. (4) A life expectancy of at least more than 6 months.According to patients desires, they were assigned into two groups: assay-directed therapy group and physician's-choice therapy group, patients' clinical and pathological characteristics, response rate to chemotherapy and progression-free survival (PFS) were compared between two groups. RESULTS: A total of 113 patients with recurrent epithelial ovarian cancer were prospectively enrollmented to assay-directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There was no difference in median age,types of recurrence, surgical-pathological stage, pathological type, tumor grade, times of recurrence, residual disease at secondary cytoreductive surgery between assay-directed group and physician's-choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57, P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control group 25% (7/28) were significantly different (P = 0.010), and the median PFS between two groups were also significantly different (5 months and 2 months, respectively, P = 0.003). CONCLUSION: ATP-TCA directed chemotherapy could improve ORR and PFS in patients with recurrent epithelial ovarian cancer, especially in platinum-resistant patients.

Nerve plane-sparing radical hysterectomy: a simplified technique of nerve-sparing radical hysterectomy for invasive cervical cancer.

BACKGROUND: In order to simplify the complicated procedure of nerve-sparing radical hysterectomy, a novel technique characterized by integral preservation of the autonomic nerve plane has been employed for invasive cervical cancer. The objective of this study was to introduce the nerve plane-sparing radical hysterectomy technique and compare its efficacy and safety with that of nerve-sparing radical hysterectomy. METHODS: From September 2006 to August 2010, 73 consecutive patients with International Federation of Gynecology and Obstetrics stage IB to IIA cervical cancer underwent radical hysterectomy with two different nerve-sparing approaches. Nerve-sparing radical hysterectomy was performed for the first 16 patients (nerve-sparing radical hysterectomy group). The detailed autonomic nerve structures were identified and separated by meticulous dissection during this procedure. After January 2008, the nerve plane-sparing radical hysterectomy procedure was developed and performed for the next 57 patients (nerve plane-sparing radical hysterectomy group). During this modified procedure, the nerve plane (meso-ureter and its extension) containing most of the autonomic nerve structures was integrally preserved. The patients' clinicopathologic characteristics, surgical parameters, and outcomes of postoperative bladder function were compared between the two groups. RESULTS: There were no significant differences between the nerve plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups regarding age, International Federation of Gynecology and Obstetrics stage, pathological type, preoperative treatment, or need for intraoperative blood transfusion. The nerve plane-sparing radical hysterectomy group had a higher body mass index than that of the nerve-sparing radical hysterectomy group (P = 0.028). The mean surgical duration in the nerve plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups were (262 ± 46) minutes and (341 ± 36) minutes (P < 0.01). On the 8th postoperative day, 41 (71.9%) patients in the nerve plane-sparing radical hysterectomy group and nine (56.3%) patients in the nerve-sparing radical hysterectomy group had a postvoid residual urine volume of < 100 ml (P = 0.233). The median duration of catheterization was eight days (range 8 - 23 days) for the nerve plane-sparing radical hysterectomy group and eight days (range 8 - 22 days) for the nerve-sparing radical hysterectomy group (P = 0.509). Neither surgery-related injury nor pathologically positive margins were reported in either group. CONCLUSION: Nerve plane-sparing radical hysterectomy is a reproducible and simplified modification of nerve-sparing radical hysterectomy, and may be preferable to nerve-sparing radical hysterectomy for treatment of early-stage invasive cervical cancer.

[Impact of squamous cell carcinoma antigen in patients with recurrent squamous cell carcinoma of the uterine cervix].

OBJECTIVE: To investigate the impact of squamous cell carcinoma antigen (SCCAg) in patients with recurrent squamous cell carcinoma of the uterine cervix. METHODS: Totally 72 patients with recurrent squamous cell carcinoma of the uterine cervix treated at the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, between 1999 and 2005 were retrospectively analyzed to investigate the impact of SCCAg on diagnosis and prognosis by univariate and multivariate analysis. RESULTS: This study included 30 patients with recurrent disease after primary radical surgery and 42 patients with recurrent cervical cancer after radio-chemotherapy. Sixty one patients (85%) had serum SCCAg elevated (>or=1.5 pg/L), and 20 of these (28%) had an increase of SCCAg before clinical manifestation of relapse. The median leading time was 3 months (range: 1-13 months). Forty five patients had no symptoms with only SCCAg elevation, and 15 patients experienced leg edema and (or) sciatic pain, 7 patients suffered from irregular bleeding and 5 patients had symptoms resulting from distant metastasis. Thirty three patients were diagnosed by histology biopsy and (or) cytology, 39 patients were diagnosed with SCCAg elevation and clinical and radiological examinations, 29 of these patients were diagnosed only by SCCAg elevation and CT or MRI. Fourteen patients recurred limited to the cervix or to the cervix and adjacent tissues (central recurrence), 31 cases recurred at pelvis, and 20 patients with distant metastasis and 7 patients suffered from pelvic recurrence and distant metastasis. Twenty three cases received salvage therapy including surgery for patients recurring after definitive radiotherapy and radiotherapy and or conform radiotherapy for patients after primary radical surgery, 46 patients were given palliative chemotherapy and or radiotherapy, and 3 patients refused any treatment. The median and mean survival time were 11 months and 23 months respectively (2-62 months). The 3-year, 5-year overall survival rate were 25% and 19% respectively. Univariate analysis showed SCCAg elevation before primary treatment, grade, recurrent site, treatment method, SCCAg>or=10 pg/L, SCCAg elevation during treatment, and SCCAg not within normal after treatment were correlated with 3-year survival rate. Twenty patients had an increase of SCCAg before clinical manifestation of relapse compared with other patients who did not, and the 3-year survival rate was not significantly different (22% vs 27%). Multivariate analysis revealed that only grade and treatment methods were independent risk factors. CONCLUSION: The impact of the SCCAg in recurrent squamous cell carcinoma of the uterine cervix needs further study.

[Synchronous primary cancers of the endometrium and ovary: review of 43 cases].

OBJECTIVE: To investigate the clinical and pathological characteristics, treatment methods, and prognosis of synchronous primary cancers of the endometrium and ovary. METHODS: The clinical data of 43 patients with synchronous primary cancers of the endometrium and ovary were retrospectively reviewed. The survival was calculated by Kaplan-Meier method and compared using the log-rank test. RESULTS: The median age at diagnosis was 49 years (range, 28-73 years). The most common symptoms were abnormal vaginal bleeding (69.8%) and abdominal or pelvic pain (44.2%).Pelvic masses were found in 39.5% of the patients and enlarged corpus in 27.9% at physical examination, while pelvic masses were found in 67.4% of the 43 patients (29 cases) and thickening or abnormal endometrium in 23.3% (10 cases) during ultrasound examination. Of 25 patients examined by CT/MRI, pelvic masses were found in 13 cases and enlarged uterus in 11 cases. All 15 patients who underwent endometrial biopsies were proven to have endometrial carcinomas. Serum CA125 level was found to be elevated in 22 of the 34 examined cases (64.7%) with a median value of 500 U/ml (range, 39-3439 U/ml). FIGO stages of endometrial carcinomas: IA 18 cases, IB 20 cases, IC 2 cases, IIA 3 cases; Stages of ovarian carcinomas: IA 19 cases, IB 4 cases, IC 7 cases, II 4 cases, III C 9 cases. Twenty-four patients (55.8%) were in stage I both endometrial and ovarian carcinomas. Thirty-one patients underwent total hysterectomy plus bilateral salpingo-oophorectomy with omentectomy and appendectomy, meanwhile, 12 patients had pelvic lymph node dissection. Thirty-eight of the 43 patients (88.4%) had a pathologically proven endometrial adenocarcinoma. The predominant ovarian histology was endometrioid or mixed tumor with endometrioid components (30/43, 69.8%). Postoperatively, 26 patients (60.5%) received adjuvant chemotherapy alone, 12 had chemotherapy plus radiotherapy, only one patient had radiation alone and the remaining 4 cases received no adjuvant treatment. The 3- and 5-year survival rates of the group were 87.4% and 71.1%, respectively. The 3- and 5-year survival rates of patients with both endometrioid and ovarian carcinomas were higher than that of those with non-endometrioid or mixed subtypes (93.8%, 82.0% vs. 79.7%, 69.0%). The 3-year and 5-year survival rates of patients with early stage disease were better than those of the other patients (93.3%, 93.3% vs. 69.7%, 36.7%). Recurrence developed in 15 patients (34.9%). It was showed by univariate analysis that lower CA125 level, early FIGO stage, and adjuvant chemotherapy plus radiotherapy significantly and positively affect the 5-year survival rates, while only early FIGO stage and chemotherapy plus radiotherapy were revealed by multivariate analysis as independent prognostic factors. CONCLUSION: Synchronous primary cancers of the endometrium and ovary are different from either primary endometrial carcinoma or ovarian cancer, while it can usually be detected in early stage and with a good prognosis. The impact of the CA125 level on prognosis needs to be further studied. Surgical treatment alone may be enough for early stage patients. Chemotherapy plus radiotherapy may be necessary for advanced stage patients.

[Analysis of 20 cases of pelvic tuberculosis initially suspected of ovarian carcinoma].

OBJECTIVE: To analyze the clinical characteristics of female pelvic tuberculosis for the differentiation from ovary carcinoma. METHODS: Twenty patients who were confirmed having pelvic tuberculosis from March 1994 to May 2002 were retrospectively studied. RESULTS: Poor economic condition, history of tuberculosis or contact with tuberculosis, and fever were among the most important factors in differentiating pelvic tuberculosis from advanced ovarian cancer. Pelvic mass and ascites were present in all of the 20 patients, abdominal distension in 16, abdominal pain in 12, fever in 16, lost of weight in 13, and diarrhea in 6. The level of serum CA125 ranged from 65 U/L to 1,069 U/L. Peritoneal effusion cytology was studied in 16 cases before operation. CONCLUSIONS: The clinical differentiation of female pelvic tuberculosis from ovary carcinoma was difficult. Pelvic tuberculosis should be considered in young women presented with pelvic mass, ascites, fever, an elevated CA125 level and negative cytology, and with a history of tuberculosis or contact with tuberculosis.