The relationship between serum CA-125 level and recurrence in surgical stage I endometrial cancer patients.

BACKGROUND: The majority of patients diagnosed with early stage endometrial cancer have a favorable prognosis; however, approximately 10% to 15% experience a recurrence. Therefore, the aim of the present study was to evaluate whether postoperative carbohydrate antigen 125 (CA-125) levels could be used to predict recurrence and recurrence-free survival (RFS) in patients with surgical stage I endometrial cancer. METHODS: We enrolled a total of 518 patients with stage I endometrial cancer who underwent surgical treatment between January 2010 and March 2019. Serum CA-125 levels were measured prior to surgery, as well as 6 to 12 months after surgery. Subsequently, the correlations between the CA-125 levels, cancer recurrence, and RFS were analyzed. RESULTS: Although the preoperative CA-125 level was not associated with the risk of cancer recurrence, the postoperative CA-125 level was found to be the only independent predictor of recurrence in both univariate and multivariate analyses. Additionally, we found that a postoperative CA-125 cutoff value of 13.75 U/mL yielded the best sensitivity and specificity for predicting cancer recurrence. Patients with a postoperative CA-125 level ≥13.75 U/mL, and those with a level <13.75 U/mL, had a median time to recurrence and a 5-year RFS rate of 35.5 vs 50.5 months and 84.7 vs 94.4%, respectively. Additionally, postoperative CA-125 levels were not found to be correlated with preoperative levels. CONCLUSION: In patients with stage I endometrial cancer, a postoperative CA-125 level ≥13.75 U/mL was found to be significantly correlated with a higher recurrence rate, as well as a shorter RFS. Therefore, obtaining a follow-up CA-125 level within 6 to 12 months after staging surgery may be a promising noninvasive biomarker for predicting recurrence.

Comparing paclitaxel-platinum with ifosfamide-platinum as the front-line chemotherapy for patients with advanced-stage uterine carcinosarcoma.

BACKGROUND: Uterine carcinosarcoma (UCS) is a rare but highly lethal disease. Adjuvant chemotherapy is highly recommended for advanced UCS. To date, the standard chemotherapy regimen is still uncertain, although two regimens as paclitaxel-platinum (PP) and ifosfamide-platinum (IP) regimens are most commonly used. The aims of the current study attempt to compare both regimens in the management of advanced UCS patients. METHODS: We evaluated advanced UCS patients who were treated either with PP or with IP after primary cytoreductive surgery in single institute retrospectively. The clinical-pathological parameters, recurrence, and survival were recorded. RESULTS: A total of 16 patients were analyzed. Twelve patients received adjuvant PP therapy, and the remaining four patients received IP therapy. The median follow-up time was 28 months, ranging from 3.8 months to 121 months. Disease-related death occurred in 10 patients (62.5%). The median progression-free survival was 4.9 months, ranging from 3.8 months to 36.5 months in IP, and 23.1 months, ranging from 9.3 months to 121 months in PP, with statistically significant difference (p = 0.04). The median overall survival was 9.5 months (ranging from 3.8 months to 36.5 months) and 28.7 months (ranging from 10.3 months to 121 months) in IP and PP, respectively, without statistically significant difference (p = 0.06). Presence of pelvic and para-aortic lymphadenopathy and deep myometrial invasion (>1/2) were associated with worse prognosis by univariate analysis. No prognostic factor could be identified using multivariate analysis model. CONCLUSION: In the current study, due to extremely little number of subjects enrolled, the advantage of using paclitaxel-platinum regimen in the management of advanced UCS was still unclear, although a certain trend of favoring was supposed. We are looking forward to seeing more studies to identify the approximate regimen in the management of this highly lethal disease.

Synergistic therapeutic effect of low-dose bevacizumab with cisplatin-based chemotherapy for advanced or recurrent cervical cancer.

BACKGROUND: Cisplatin-based chemotherapy (CBC) is highly efficacious for advanced cervical cancer; its efficacy can be enhanced by combining with 15 mg/kg (standard dose) bevacizumab (BEV). However, this standard dose is associated with various adverse events (AEs). Therefore, in this retrospective study, we analyzed the survival outcomes and AEs in patients with advanced or recurrent cervical cancer treated with CBC in combination with BEV 7.5 mg/kg. METHODS: Registered patient data were retrieved between October 2014 and September 2019, and 64 patients with advanced or recurrent cervical cancer treated with CBC + BEV (n = 21) or CBC alone (n = 43) were analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were the frequency and severity of AEs. The Cox proportional-hazards model was applied to explore prognostic factors associated with PFS and OS. RESULTS: The 1-, 2-, and 3-year PFS rates (95% CI) were 36.24% (22.0-50.5), 20.7% (9.8-34.2), and 17.7% (7.7-31.1) for the CBC group; and 71.4% (47.1-86.0), 51.0% (27.9-70.1), and 51.0% (27.9-70.1) for the CBC + BEV group, respectively. The 1-, 2-, and 3-year OS rates were 62.6% (46.4-75.18), 32.4% (18.8-46.9), and 23.2% (11.2-37.6) for the CBC group; and 85.7% (61.9-95.1), 66.6% (42.5-82.5), and 55.5% (27.1-76.7) for the CBC + BEV group, respectively. The CBC + BEV group presented higher PFS and OS rates, p = 0.003 and p = 0.005, respectively. Proteinuria (6 vs 9, p = 0.025) and hypertension (0 vs 10, p < 0.001) were less common, but anemia was more common in the CBC group (35 vs 11, p = 0.021). CONCLUSION: Overall, CBC + BEV significantly improved the PFS and OS compared with CBC alone. CBC + BEV also prevents severe AEs and hence is an efficacious and safe therapeutic option.

Right postoperative pleural effusion and pulmonary embolism following laparoscopic gynecological surgery: A rare case report and PRISMA-driven systematic review.

The incidence of postlaparoscopic pleural effusion and pulmonary embolism were rare. However, it might be life-threatening. Therefore, confirming the risk factor and management is important. We present a 53-year-old woman with ovarian endometriosis arranged for laparoscopic surgery. However, desaturation was noted on postoperation day 1. Chest radiograph and chest computed tomography showed pleural effusion and pulmonary embolism. Pleural pigtail insertion was performed and anticoagulant medication, albumin, and lasix were given. The patient's recovery was uneventful. Several factors have been advanced to explain including the prolonged duration of the operation. Management options include supplemental oxygen therapy, and pigtail catheter insertion. Mechanical prophylaxis (sequential compression devices and graduated compression stockings) is sufficient for venous thromboembolism prevention.

Prognostic Factors of Early Stage Epithelial Ovarian Carcinoma.

We aimed to determine prognostic factors of early stage (I/II) epithelial ovarian carcinoma (EOC) including clinicopathologic and chemotherapeutic regimens. Four hundred and thirty-seven women who underwent primary staging surgery with adjuvant chemotherapy between January 1, 2000 and December 31, 2010 were retrospectively reviewed and analyzed from two medical centers. The prognostic factors were determined from multivariate survival analyses using Cox regression models. The majority of women were diagnosed with stage Ic (244/437, 55.8%). The histopathologic types were clear cell (37.5%), endometrioid (27.2%), serous (14.0%), and mucinous (13.3%). Fifty-seven percent (249/437) of the women received taxane-based (platinum plus paclitaxel) regimens and 43.0% received non-taxane (platinum plus cyclophosphamide) regimens as frontline adjuvant chemotherapy. Clear cell tumors (adjusted Hazard ratio (aHR) 0.37, 95% confidence interval (CI) 0.21⁻0.73, p = 0.001) showed better 5-year disease-free survival (DFS) than serous tumors. Women diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage II (aHR 5.97, 95% CI = 2.47⁻14.39, p < 0.001), grade 3 tumor without clear cell (aHR 2.28, 95% CI = 1.02⁻5.07, p = 0.004) and who received 3⁻5 cycles of non-taxane regimens (aHR 3.29, 95% CI = 1.47⁻7.34, p = 0.004) had worse 5-year overall survival (OS). Clear cell histology treated with taxane-based regimens showed significantly higher 5-year DFS (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21⁻0.93, p = 0.043) and 5-year OS (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13⁻0.70, p = 0.005) than those treated with non-taxane-based regimens. We conclude that stage, tumor grade, and chemotherapeutic regimens/cycles are independent prognostic factors for early stage ovarian cancer.

Malignant perivascular epithelioid cell tumor in the female genital tract: Preferred reporting items for systematic reviews and meta-analyses.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor, located at various anatomic sites, including the female genital tract. This study aimed to evaluate the clinicopathological characteristics of patients with PEComa arising from the female genital tract. METHODS: A retrospective study was conducted in Taipei Veterans General Hospital (Taipei VGH) between 2008 and 2018. All published English cases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were also included in the current review. RESULTS: A total of 114 women from PRISMA and 3 women from Taipei VGH were identified. The uterus was the most commonly involved site (82/114, 71.9%), followed by the cervix (12/114, 10.5%). Immunohistochemical staining showed that nearly all gynecological PEComas were positive for human melanoma black 45 (113/114, 99.1%). More than half of the gynecological PEComas were immunoreactive for desmin (50/85, 58.8%). Multi-modality treatment, including surgery and mammalian target of rapamycin (mTOR) inhibitors as targeted therapy, provided long-term disease-free survival (cure rate ranging from 50% to 100%, based on the different anatomic sites of the female genital tract). CONCLUSION: Multi-modality treatment, including cytoreductive surgery and mTOR inhibitors with/without chemotherapy and/or radiation, should be considered for the management of women with PEComas in the genital tract.

Neurofibroma involving obturator nerve mimicking an adnexal mass: a rare case report and PRISMA-driven systematic review.

BACKGROUND: Pelvic masses are a common gynecologic problem, and majority of them are diagnosed as ovarian tumors finally. Sometimes, it is hard to distinguish the origin of these pelvic masses. The following case is a solitary neurofibroma arising from the right-side obturator nerve, which was impressed as a right-side ovarian tumor initially. We reported this case, and also performed a PRISMA-driven systematic review to summary the similar cases in the literature. This review includes image, molecular and pathological findings and outcome of neurofibroma. CASE PRESENTATION: A 33-year-old woman with a regular menstrual period denied any symptoms or signs. During her physical check-up, image examination revealed a right-side heterogeneous pelvic mass; it was suggestive of a complex of right-side ovarian tumor. A provisional diagnosis of retroperitoneal pelvic mass, probably a benign ovarian tumor, was made. Excision of the right-side pelvic mass was performed. We sent the specimens for frozen pathology, which indicated neurofibroma and lipomatous tumor and that the possibility of liposarcoma cannot be excluded. A segment of the obturator nerve was attached to the tumor and was severed. A right-side obturator nerve tear during tumor excision was observed, and a neurosurgeon was consulted for obturator nerve grafting and repair. The patient complained of mild weakness and paresthesia affecting the right leg, and we consulted a rehabilitation doctor for neuron injury. The patient's recovery was uneventful, and she was discharged eight days after the drain was removed. Further rehabilitation treatment was arranged. CONCLUSION: A neurofibroma is an uncommon pelvic retroperitoneal tumor, and it can be misdiagnosed as an adnexal mass. To our knowledge, this is a rare case of a solitary neurofibroma arising from the obturator nerve. It usually does not have any neurological deficit. We present this case to demonstrate that pelvic neurofibroma can be mistaken for an adnexal mass. This fact should be borne in mind during the diagnosis process.

The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels.

An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes.

Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma.

The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics.

Triage of Atypical Glandular Cell by SOX1 and POU4F3 Methylation: A Taiwanese Gynecologic Oncology Group (TGOG) Study.

INTRODUCTION: Invasive procedures including loop electrosurgical excision, cervical conization, and endometrial sampling are often recommended when atypical glandular cells (AGC) are detected on Pap smear with unsatisfactory colposcopy. These invasive procedures may result in patient anxiety, increased medical expense, and increasing the risk of preterm delivery in subsequent pregnancies. This study was performed to assess methylation biomarkers in the triage of AGC on Pap smear for invasive procedures. METHODS: We conducted a multicenter study in 13 medical centers in Taiwan from May 2012 to May 2014. A total of 55 samples diagnosed "AGC not otherwise specified" (AGC-NOS) were included. All patients with AGC underwent colposcopy, cervical biopsy, endometrial sampling, and conization if indicated. Multiplex quantitative methylation-specific polymerase chain reaction (QMSPCR) was performed. Sensitivity, specificity, and accuracy were calculated for detecting CIN3+ and endometrial complex hyperplasia. RESULTS: In 55 patients with AGC, the sensitivity for methylated (m) SOX1m, PAX1 m, ZNF582m,PTPRRm, AJAP1m, HS3ST2m, and POU4F3m for detecting CIN3+ and endometrial complex hyperplasia lesions was 100, 86, 71, 86, 86, 57, and 100%; specificity was 67, 79, 85, 50, 52, 96, and 52%, respectively. Testing for high risk-HPV had a sensitivity of 57% and specificity of 75% for CIN3+ and endometrial complex hyperplasia lesions. CONCLUSION: Methylated (m) SOX1m and POU4F3m could be new methylation biomarkers for detection of CIN3+ and endometrial complex hyperplasia in AGC. Women with AGC and positive SOX1m / POU4F3m, colposcopy, cervical conization or endometrial sampling should be considered.

Impact of ovarian preservation in women with endometrial cancer.

BACKGROUND: Bilateral salpingo-oophorectomy (BSO) is standardly performed in the treatment of endometrial cancer. The purpose of this study was to evaluate the impact of ovarian preservation on the outcome of patients with endometrial cancer. METHODS: A retrospective cohort study was performed using the 2000-2010 database of endometrial cancer patients who were treated at Taipei Veterans General Hospital. Information regarding patient age, pathologic reports, and follow-up results was abstracted from medical records. RESULTS: Five hundred and twenty-nine patients were reviewed in this study. Mean age and follow-up duration were 55.7 ± 11.4 years and 37.5 ± 30.1 months, respectively. The median disease-free survival was 31.2 months (range 0.2-126.9 months). There were no significant differences in disease-free survival between stage I patients with ovarian preservation versus those with oophorectomy (p = 0.473). In a multivariate Cox model, ovarian preservation had no effect on disease-free survival [hazard ratio (HR) = 2.72; 95% confidence interval (CI), 0.48-15.59]; however, it was not significantly related to stage and para-aortic lymph node involvement. CONCLUSION: Ovarian preservation may be considered in premenopausal women with early-stage low-risk endometrial cancer.

Serum cytokeratin-19 fragment (Cyfra 21-1) is a prognostic indicator for epithelial ovarian cancer.

OBJECTIVES: Cytokeratin 19 is significant for indicating cancer cells, and Cyfra 21-1 is a fragment of cytokeratin 19. This retrospective study was designed to define the prognostic value of serum Cyfra 21-1 in epithelial ovarian cancers (EOC). MATERIALS AND METHODS: Serum Cyfra 21-1 concentration was obtained from 42 patients with EOC prior to treatment. Various prognostic aspects were examined using univariable and multivariable analyses. The standard serum marker cancer antigen 125 was measured simultaneously and compared in this analysis. RESULTS: Serum levels of both Cyfra 21-1 and cancer antigen 125 were associated with positive retroperitoneal lymph nodes and platinum resistance; higher levels of Cyfra 21-1 (3.0 ng/mL as the cut-off) were associated with shorter disease-free survival (16 months vs. 28 months, p = 0.001) and overall survival (29 months vs. 41 months, p = 0.007) than lower levels. Further univariable analysis showed that Cyfra 21-1, poor differentiation, and retroperitoneal lymph node metastasis were related to platinum resistance and mortality. Multivariable analysis indicated retroperitoneal lymph node metastasis and serum Cyfra 21-1 were independent risk factors for both disease-free survival and overall survival. CONCLUSION: The pretreatment level of serum Cyfra 21-1 had remarkable prognostic significance for EOC, indicating poor survival when it was elevated above 3.0 ng/mL.

Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study.

BACKGROUND: Cancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors. METHODS: Ovarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test. RESULTS: Each cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens. CONCLUSIONS: Ovarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors.

Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

A tumor necrosis factor-α inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid.

OBJECTIVE: To determine whether a tumor necrosis factor-α (TNF-α) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis. DESIGN: Experimental clinical study. SETTING: University hospital. PATIENT(S): Twelve women with chocolate cysts and 12 control women without endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-α inhibitor. RESULT(S): We found that CH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-α, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-α retarded development and induced apoptosis. Important, adalimumab, a TNF-α inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF. CONCLUSION(S): These data collectively highlight the crucial role of TNF-α in CH-PF-induced embryotoxicity and suggest that TNF-α inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility.

The role of secondary cytoreductive surgery in patients with recurrent epithelial ovarian, tubal, and peritoneal cancers: a comparative effectiveness analysis.

Background. All published reports concerning secondary cytoreductive surgery for relapsed ovarian cancer have essentially been observational studies. However, the validity of observational studies is usually threatened from confounding by indication. We sought to address this issue by using comparative effectiveness methods to adjust for confounding. Methods. Using a prospectively collected administrative health care database in a single institution, we identified 1,124 patients diagnosed with recurrent epithelial, tubal, and peritoneal cancers between 1990 and 2009. Effectiveness of secondary cytoreductive surgery using the conventional Cox proportional hazard model, propensity score, and instrumental variable were compared. Sensitivity analyses for residual confounding were explored using an array approach. Results. Secondary cytoreductive surgery prolonged overall survival with a hazard ratio (95% confidence interval) of 0.76 (range 0.66-0.87), using the Cox proportional hazard model. Propensity score methods produced comparable results: 0.75 (range 0.64-0.86) by nearest matching, 0.73 (0.65-0.82) by quintile stratification, 0.71 (0.65-0.77) by weighting, and 0.72 (0.63-0.83) by covariate adjustment. The instrumental variable method also produced a comparable estimate: 0.75 (range 0.65-0.86). Sensitivity analyses revealed that the true treatment effects may approach the null hypothesis if the association between unmeasured confounders and disease outcome is high. Conclusions. This comparative effectiveness study provides supportive evidence for previous reports that secondary cytoreductive surgery may increase overall survival for patients with recurrent epithelial, tubal, and peritoneal cancers.

Primary treatment and prognostic factors of small cell neuroendocrine carcinoma of the uterine cervix: a Taiwanese Gynecologic Oncology Group study.

BACKGROUND: Our aims were to investigate the treatment and clinicopathological variables in relation to prognosis in small cell neuroendocrine cervical carcinoma (SCNECC). PATIENTS AND METHODS: Clinical data of SCNECC patients with International Federation of Gynaecology and Obstetrics (FIGO) stages I-IV treated between 1987 and 2009 at member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. RESULTS: Of the 179 eligible patients, 104 were of FIGO stage I, 19 stage IIA, 23 stage IIB, 9 stage III, and 24 stage IV. The median failure-free survival (FFS) was 16.0 months, and the median cancer-specific survival (CSS) was 24.8 months. In multivariate analysis, FIGO stage and lymph node metastasis were selected as independent variables in stages I-IV. In stages IIB-IVB, primary treatment containing etoposide and platinum for at least 5 cycles (EP5+) (n=16) was associated with significantly better 5-year FFS (42.9% versus 11.8%, p=0.041) and CSS (45.6% versus 17.1%, p=0.035) compared to other treatments (n=40). Furthermore, concurrent chemoradiation with EP5+ (CCRT-EP5+) was associated with even better 5-year FFS (62.5% versus 13.1%, p=0.025) and CSS (75.0% versus 16.9%, p=0.016). CONCLUSIONS: FIGO stage and lymph node metastasis are significant prognostic factors in SCNECC. In stages IIB-IVB, CCRT-EP5+ might be the treatment of choice, which could be also true for earlier stages. Despite limitations of a retrospective study spanning a long time period and heterogeneous managements, the results provide an important basis for designing future prospective studies.

Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients.

Recent studies have indicated that Aurora B expression is related to cell proliferation and prognosis in many cancers, but its association with epithelial ovarian carcinoma is not fully understood. Therefore, we examined the Aurora B kinase expression in epithelial ovarian cancer patients. Using immunohistochemistry, the expression levels of Aurora B and phosphohistone H3 (Ser(10)) (mitosis-specific marker) were measured in 156 patients with epithelial ovarian cancer. The expression levels of Aurora B at the protein and messenger RNA levels were examined using Western blotting and reverse transcriptase polymerase chain reaction. In total, 53 tumorous ovarian samples (34.0%) showed Aurora B overexpression, which was significantly higher than that found in the 15 normal ovarian tissue samples (0%, p = 0.006). The overexpression of Aurora B was also significantly higher in cases showing phosphohistone H3 (Ser(10)) overexpression (44.3% vs. 27.4%, p = 0.03). In addition, the expression of Aurora B in poorly and moderately differentiated carcinomas of the ovary was significantly higher than in well-differentiated carcinomas (53.6% vs. 28.2% vs.10.0%, respectively, p = 0.02). The overexpression of Aurora B was significantly higher in cases with lymph node metastasis (p = 0.01) and a positive ascites cytology (p = 0.008). Overall, the Aurora B overexpression group demonstrated a significantly shorter progression-free survival (p = 0.001) and overall survival (p = 0.023) than the Aurora B low expression group using univariate analysis (log-rank statistic). Aurora B is an effective predictor of aggressive epithelial ovarian carcinoma in terms of differentiation, metastasis, and prognosis.

Expression of Aurora kinase A and B in normal and malignant cervical tissue: high Aurora A kinase expression in squamous cervical cancer.

OBJECTIVE: Aurora kinases such as Aurora A and B are key regulators of mitosis and tumorigenesis and have been reported to be overexpressed in various malignancies. However, the expression of Aurora kinases in normal and neoplastic cervical tissues remains undetermined. STUDY DESIGN: Immunohistochemical expression of Aurora A and B kinase was examined in 20 normal cervix, 35 cervical intraepithelial neoplasm 3 (CIN 3) and 95 cervical cancers, including squamous cell carcinoma (SCC) (n=76) and adenocarcinoma (AC) (n=19). Expression of Aurora A and B kinase was confirmed by Western blot. The correlation between Aurora A and B kinases expression and the clinico-pathological parameters was analyzed by statistical analysis. RESULTS: The Aurora A and B expression was significantly increased in carcinoma and CIN 3, compared with normal cervix. However, expression of Aurora A and B showed no significant correlation between CIN 3 and cervical cancer. The nuclear expression of Aurora A showed a significantly positive correlation with the expression of Aurora B (P=0.018). The percentage of Aurora A overexpression between SCCs and ACs showed a significant difference (50% vs. 21.1%, P=0.023). However, there was no correlation of Aurora A and B expression with patient survival. CONCLUSION: According to our study, Aurora A and B overexpression is a relatively early phenomenon in the genesis of malignant epithelial neoplasm tumorigenesis. Based on the results of this study, it would be interesting to know whether Aurora kinases play a role in pathogenesis of cervical dysplasia and SCC patients.