Upregulation of NOD1 and NOD2 contribute to cancer progression through the positive regulation of tumorigenicity and metastasis in human squamous cervical cancer.

BACKGROUND: Metastatic cervical squamous cell carcinoma (CSCC) has poor prognosis and is recalcitrant to the current treatment strategies, which warrants the necessity to identify novel prognostic markers and therapeutic targets. Given that CSCC is a virus-induced malignancy, we hypothesized that the pattern recognition receptors (PRRs) involved in the innate immune response likely play a critical role in tumor development. METHODS: A bioinformatics analysis, qPCR, IHC, immunofluorescence, and WB were performed to determine the expression of NOD1/NOD2. The biological characteristics of overexpression NOD1 or NOD2 CSCC cells were compared to parental cells: proliferation, migration/invasion and cytokines secretion were examined in vitro through CCK8/colony formation/cell cycle profiling/cell counting, wound healing/transwell, and ELISA assays, respectively. The proliferative and metastatic capacity of overexpression NOD1 or NOD2 CSCC cells were also evaluated in vivo. FCM, mRNA and protein arrays, ELISA, and WB were used to identify the mechanisms involved, while novel pharmacological treatment were evaluated in vitro and in vivo. Quantitative variables between two groups were compared by Student's t test (normal distribution) or Mann-Whitney U test (non-normal distribution), and one-way or two-way ANOVA was used for comparing multiple groups. Pearson χ2 test or Fisher's exact test was used to compare qualitative variables. Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. P values of < 0.05 were considered statistically significant. RESULTS: NOD1 was highly expressed in CSCC with lymph-vascular space invasion (LVSI, P < 0.01) and lymph node metastasis (LM, P < 0.01) and related to worse overall survival (OS, P = 0.016). In vitro and in vivo functional assays revealed that the upregulation of NOD1 or NOD2 in CSCC cells promoted proliferation, invasion, and migration. Mechanistically, NOD1 and NOD2 exerted their oncogenic effects by activating NF-κb and ERK signaling pathways and enhancing IL-8 secretion. Inhibition of the IL-8 receptor partially abrogated the effects of NOD1/2 on CSCC cells. CONCLUSIONS: NOD1/2-NF-κb/ERK and IL-8 axis may be involved in the progression of CSCC; the NOD1 significantly enhanced the progression of proliferation and metastasis, which leads to a poor prognosis. Anti-IL-8 was identified as a potential therapeutic target for patients with NOD1high tumor.

Blood-based DNA methylation profiling for the detection of ovarian cancer.

OBJECTIVES: Ovarian cancer is a fatal gynecological cancer due to the lack of effective screening strategies at early stage. This study explored the utility of DNA methylation profiling of blood samples for the detection of ovarian cancer. METHODS: Targeted bisulfite sequencing was performed on tissue (n = 152) and blood samples (n = 373) obtained from healthy women, women with benign ovarian tumors, or malignant epithelial ovarian tumors. Based on the tissue-derived differentially-methylated regions, a supervised machine learning algorithm was implemented and cross-validated using the blood-derived DNA methylation profiles of the training cohort (n = 178) to predict and classify each blood sample as malignant or non-malignant. The model was further evaluated using an independent test cohort (n = 184). RESULTS: Comparison of the DNA methylation profiles of normal/benign and malignant tumor samples identified 1272 differentially-methylated regions, with 49.4% hypermethylated regions and 50.6% hypomethylated regions. Five-fold cross-validation of the model using the training dataset yielded an area under the curve of 0.94. Using the test dataset, the model accurately predicted non-malignancy in 96.2% of healthy women (n = 53) and 93.5% of women with benign tumors (n = 46). For patients with malignant tumors, the model accurately predicted malignancy in 44.4% of stage I-II (n = 9), 86.4% of stage III (n = 59), 100.0% of stage IV tumors (n = 6), and 81.8% of tumors with unknown stage (n = 11). Overall, the model yielded a predictive accuracy of 89.5%. CONCLUSIONS: Our study demonstrates the potential clinical application of blood-based DNA methylation profiling for the detection of ovarian cancer.

Long-term impact of lymphadenectomies in patients with low-grade, early-stage uterine endometrial stroma sarcoma.

AIM: The aim of our study was to investigate the lymph node metastasis (LNM) rate and effect of lymph node dissection (LND) in patients with stage I, low-grade endometrial stromal sarcoma (LGESS). METHODS: Patients with stage I LGESS (n = 119) that underwent surgery from July 1969 to July 2017, following up over 48 years at the China National Cancer Center were retrospectively analyzed in this study. RESULTS: Surgical records and consulting data for patients with LGESS were analyzed to find that 47 patients received systematic pelvic LND. The number of patients with menopause in the LND(+) group were significantly lower than those in LND(-) group (2.1% vs 22.2%, P = 0.005), meanwhile, patients received bilateral salpingo-oophorectomy procedure in LND(+) group were significantly higher than LND(-) (97.9% vs 58.3%, P < 0.001). Neither progression-free survival nor overall survival was significantly improved in the LND(+) group even after propensity score matching although the progression-free survival has a stronger trend in LND(+) population. CONCLUSION: A systematic LND was not significantly associated with prognosis for patients with early-stage LGESS. There is no sufficient indication for a systematic LND for patients with early-stage LGESS. A systematic LND might be necessary if enlarged lymph nodes were detected by image graphology or observation during surgery.

[Clinical analysis of 32 cases with neuroendocrine carcinoma of the uterine cervix in early-stage disease].

OBJECTIVE: To investigate the survival and recurrence data after treatment in neuroendocrine carcinoma of the uterine cervix (NECUC) with stage Ib-IIa, and to analyse its prognostic factors. METHODS: Thirty-two cases of primary NECUC in early-stage disease treated from Jan. 2005 to Dec. 2013 at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences were reviewed, and their data of clinicopathologic characteristics were collected and analysed. The median age was 37 years (range, 23-57 years). The distribution by International Federation of Gynecology and Obstetrics (FIGO) clinical stage: 19 cases stage Ib1, 10 cases stage Ib2, 1 case stage IIa1, 2 cases stage IIa2. Pathologic types: 22 cases of small cell carcinoma, 1 case of atypical carcinoid, 9 cases of mixed carcinoma. The diameter of cervical tumor: 12 cases ≥4 cm, 20 cases <4 cm. All patients underwent radical hysterectomy and pelvic ± para-aortic lymphadenectomy, and 15 cases of them were preserved unilateral or bilateral ovaries. Pathologic examination showed that 25 cases with cervical deep stromal invasion thickness ≥1/2, 21 cases with lymph-vascular space invasion (LVSI), and 18 cases with pelvic and (or) para-aortic lymph nodes involvement. Ten cases were performed neoadjuvant chemotherapy (range,1-3 cycles), all patients received postoperative chemotherapy (range,3-6 cycles), and 15 patients were treated with radiotherapy after surgery. The follow-up data were updated on Jul. 2014. The median follow-up time was 18 months (range, 7-71 months). A retrospective analysis was conducted to analyse the survival and recurrence data,and to explore the prognostic factors of NECUC. RESULTS: Thirteen patients died during the follow-up period. The cumulative progression-free survival (PFS) of 2 and 5 years were respectively 54.2% and 38.1%, and the estimated median PFS was 29 months. The cumulative overall survival (OS) of 2 and 5 years were respectively 56.1% and 44.9%, and the estimated median OS was 31 months. Fourteen cases had recurrence, and the median recurrence time was 9 months (range, 3-30 months). Recurrent or metastatic sites: 2 cases in pelvis, 4 cases in liver, 3 cases in lung, 3 cases in adrenal glands, 3 cases in bones, 2 cases in brain, 1 case in pancreas, 1 case in lymph nodes of para-aorta and neck, and 3 cases had metastasis in two or more organs. Thirteen cases with recurrence died of disease, and another one is alive with disease. The univariate analysis showed that lesion size of the cervix and FIGO stage were significant prognostic factors (P<0.01), while age, tumor components, deep invasion in cervical stromal, LVSI, pelvic and (or) para-aortic lymph nodes involvement, neoadjuvant chemotherapy, adjuvant radiotherapy and preserving ovaries were not significantly associated with prognosis (all P>0.05). CONCLUSION: The prognosis of NECUC in early-stage is poor and the lesion size of the cervix and FIGO stage are prognostic factors.

[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.

Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer.

BACKGROUND: Plasma cell-free DNA (cfDNA) methylation has shown the potential in the detection and prognostic testing in multiple cancers. Herein, we thoroughly investigate the performance of cfDNA methylation in the detection and prognosis of ovarian cancer (OC). METHODS: The OC-specific differentially methylated regions (DMRs) were identified by sequencing ovarian tissue samples from OC (n = 61), benign ovarian disease (BOD, n = 49) and healthy controls (HC, n = 37). Based on 1,272 DMRs, a cfDNA OC detection model (OC-D model) was trained and validated in plasma samples from patients of OC (n = 104), BOD (n = 56) and HC (n = 56) and a prognostic testing model (OC-P model) was developed in plasma samples in patients with high-grade serous OC (HG-SOC) in the training cohort and then tested the rationality of this model with International Cancer Genome Consortium (ICGC) tissue methylation data. Mechanisms were investigated in the TCGA-OC cohort. FINDINGS: In the validation cohort, the cfDNA OC-D model consisting of 18 DMRs achieved a sensitivity of 94.7% (95% CI: 85.4%‒98.9%) at a specificity of 88.7% (95% CI: 78.7%‒94.9%), which outperformed CA 125 (AUC: 0.967 vs 0.905, P = 0.03). Then the cfDNA OC-P model consisting of 15 DMRs was constructed and associated with a better prognosis of HG-SOC in multivariable Cox regression analysis (HR: 0.29, 95% CI, 0.11‒0.78, P = 0.01) in the training cohort, which was also observed in the ICGC cohort using tissue methylation (HR: 0.56, 95% CI, 0.32‒0.98, P = 0.04). Investigation into mechanisms revealed that the low-risk group had higher homologous recombination deficiency and immune cell infiltration (P < 0.05). INTERPRETATION: Our study demonstrated the potential utility of cfDNA methylation in the detection and prognostic testing in OC. Future studies with a larger population are warranted. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Links between microbial compositions and metabolites during aerobic composting under amoxicillin stress was evaluated by 16S rRNA sequencing and gas chromatography-mass spectrometry: Benefit for the plant growth.

The purpose of this study was to identify the relationship between core bacteria and metabolites during aerobic composting and analyze the effects of metabolites on plant growth. The results revealed that amoxicillin might affect the generation and transformation of metabolites by reconstructs the bacterial communities. The peak area ratios (PAR) of esters and fatty acids (FAs) were increased, while sterols decreased during composting. Furthermore, the correlation analysis showed that the production of FAs, esters and sterols is strongly correlated with Oceanobacillus, Corynebacterium, Psychrobacter, Xanthomonadaceae, Pusillimonas and Gracilibacillus. Moreover, 36 key metabolites were screened out, the PAR of the propanoic acid ethyl ester and oleic acid that benefit plant growth were increased in amoxicillin groups. However, the PAR of environmental pollutants, such as n-hexadecanoic acid and 3ß, 5ß-Cholestan-3-ol is the opposite. Therefore, composting can eliminate the environmental risks caused by antibiotic residues in feces and promote plant growth.

Surgical Outcomes of Vaginal or Cervical Melanoma.

Objective: To evaluate the effectiveness of radical resection compared with non-radical resection for vaginal or cervical melanoma. Methods: We retrospectively analysed the clinical data of post-operative patients with primary lower genital tract melanoma hospitalised at Peking University Cancer Hospital between Jan 2014 and Dec 2020. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier method-plotted survival curves and univariate and multivariate Cox proportional hazards regression models were used to identify the factors associated with RFS and OS, and to calculate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs). Results: A total of 80 patients were included. Thirty-one patients had received non-radical resection, and 49 patients had received radical resection. The median patient age was 55.5 (IQR 45.3-60.0) years. Sixty-two (77.5%) patients had vaginal melanoma. Sixty-four patients (80.0%) had received post-operative adjuvant therapy. The median follow-up time was 36.0 months (95% CI 10.1-62.1 months). Sixty-four patients developed recurrence, and 44 patients died. The median RFS (mRFS) was 6.0 months (95% CI 3.4-8.6 m), and the RFS for the radical resection group was longer than that for the non-radical resection group (9.5 vs. 5.3 m), with no significant difference (P > 0.05). The median OS (mOS) was 25.9 months (95% CI 14.4-37.4 m). The mOS was 24.6 months (95% CI 10.3-38.9 m) and 25.9 months (95% CI 10.9-40.9 m) in the non-radical resection group and the radical resection group, respectively. Multivariate Cox regression analysis showed that surgical approach, infiltration depth of the tumour, lymph node metastasis, and post-operative adjuvant therapy were independent risk factors for RFS and that post-operative adjuvant therapy was an independent risk factor for OS. Conclusion: By performing multivariate analysis, which corrected for potential confounding factors, we identified surgical procedures that were associated with RFS, and we found that RFS and OS in patients with vaginal melanoma and cervical melanoma benefitted from post-operative adjuvant therapy.

An Oral Small Molecule VEGFR2 Inhibitor, Apatinib, in Patients with Recurrent or Refractory Cervical Cancer: A Real World Study.

To evaluate the efficacy and safety of apatinib, an oral antiangiogenic drug, in patients with recurrent or refractory cervical cancer as salvage treatment, we retrospectively analyzed the medical records of recurrent or refractory cervical cancer patients admitted to the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Hunan Cancer Hospital, from October 1, 2016, to December 31, 2017. Patients who progressed within 6 months after the last treatment were given apatinib orally at a dose of 250 mg daily until disease progression or unacceptable toxicity. Twenty-nine patients were enrolled in our retrospective study. Up to February 1, 2019, the median follow-up time was 18 months. The median progression-free survival was 128 days (95% confidence interval (CI): 20-540 days), and the median overall survival was 9 months (95% CI: 4-23 months). The longest period of apatinib administration was 540 days. No complete response was observed, 5 (17.2%) patients achieved partial response, and 11 (37.9%) achieved stable disease. The objective response rate and disease control rate were 17.2% and 55.1%, respectively. The most common adverse events were hypertension (G1, 65.5%, 19/29), mucositis (G1, 55.2%, 16/29), hand-foot syndrome (G1-2, 44.8%, 13/29), and proteinuria (G1-2, 20.7%, 6/29). Grade 3 proteinuria occurred in only one patient (3.4%, 1/29). Apatinib single-agent use might be an effective and tolerable choice as salvage therapy for patients with recurrent or refractory cervical cancer.

Efficient isolation, culture, purification, and stem cell expression profiles of primary tumor cells derived from uterine cervical squamous cell carcinoma.

PROBLEM: Since not too many human uterus cervical squamous cell carcinoma (CSCC) cell lines in existence, efficient isolation, culture, and purification protocols for primary CSCC cells were optimized as a tool for the study of uterus CSCC. METHOD OF STUDY: The protocols for partial multiple enzymatic digestion and explant cell culture were combined and then the resulting mixed cell component cultures were purified by magnetic-activated cell sorting. Colony-forming assay was utilized for detection of cell carcinogenesis potential, and immunofluorescence was used to detect protein expression of CSCC. Finally, flow cytometry (FCM) was performed to analyze cancer stem cells (CSCs) phenotypic markers as well as programmed cell death ligand 1(PD-L 1). RESULTS: Freshly isolated cells containing tumor cells and cancer-associated fibroblasts (CAFs) efficiently proliferate to 85% confluence on a 6 cm petri dish in 5-7 days. Anti-epithelial cell adhesion molecule antibody (EpCAM) microbeads were used to successfully separate a homogeneous subpopulation of epithelial tumor cells. Both EpCAM+ and EpCAM- cell subpopulations were able to be passaged more than 30 times. Proportions of tumor cell populations expressed CSCs markers such as CD133, CD24, aldehyde dehydrogenase 1 (ALDH1), and CD44. The vimentin+ & EpCAM- population, defined with CAFs, could express CD146 mesenchymal stem cells marker. Meanwhile, PD-L 1 was identified in most subpopulation of CD44+ cells at low passage numbers. CONCLUSION: Efficient isolation, culture, and purification protocols for primary CSCC cells were successfully built. Additionally, the profiling of CSCs cell markers might provide promising therapeutic targets and clinic strategies.

[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.

[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.

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.

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.

Clinical outcome and prognostic factors of patients with early-stage epithelial ovarian cancer.

Some subsets of early stage ovarian cancer patients experience more recurrences than others. Studies on prognostics factors gave conflicting results. We investigated consecutive 221 patients with stage I/II ovarian cancer at our institution from 1999 to 2010. Univariate and multivariate analysis of progression free survival (PFS) and overall survival (OS) were performed. After a median follow-up of 79 months, the 5-year/10-year PFS and 5-year/10-year OS were 78% /76% and 90% /87% respectively. Multivariate analysis revealed that stage as the most prominent independent prognostic factor in terms of PFS (stage I vs stage IIA vs stage IIB, Hazard Ratio (HR): 1 vs 4 vs 6.1, P < 0.05) and OS (stage I vs stage II, HR: 1 vs 2.1, P < 0.05). Peritoneal biopsy reduced the risk of recurrence by 29% (95% CI: 0.15-0.58, P < 0.05). Ascites (HR = 2.8, 95% CI: 1.2-6.6, P < 0.05) and not the first-line chemotherapy (HR = 2.6, 95% CI: 1.1-6.5, P < 0.05) contributed to decreased OS. Overall, early-stage ovarian cancer had a favorable outcome, stage was the most powerful prognostic factor.

Role of positive peritoneal cytology in FIGO stage IB to IIB cervical adenocarcinoma.

OBJECTIVE: To evaluate the prognostic relevance of positive peritoneal cytology in patients with cervical adenocarcinoma. METHODS: The present study included patients diagnosed with FIGO stage IB to IIB cervical adenocarcinoma who underwent surgery at a hospital in Beijing, China, between December 1, 2000, and December 31, 2015. Baseline data were retrieved from patient medical records and follow-up data were collected through telephone interviews. The relationship between positive peritoneal cytology and the patients' clinicopathological features, and their prognosis was analyzed using Kaplan-Meier and Cox proportional hazards modeling. RESULTS: There were 136 patients who met the inclusion criteria and participated in interviews. Peritoneal cytology was positive in 13 (9.6%) patients. The 5-year survival rate of patients with positive and negative cytology was 69.2% and 95.7%, respectively (P<0.001). The 3-year recurrence-free survival rate in the two groups was 76.2% and 91.3%, respectively (P=0.041). Cox regression analysis showed pelvic lymph node involvement and vaginal invasion to be independent adverse risk factors for survival. The recurrence rate in the positive cytology group was significantly higher than that in the negative cytology group (38.5% vs 7.3%; P=0.002). CONCLUSION: Positive peritoneal cytology in patients with cervical adenocarcinoma was associated with a poor prognosis and a higher recurrence rate, but it was not an independent prognostic factor.

[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.

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.

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.