A radiomics-based nomogram may be useful for predicting telomerase reverse transcriptase promoter mutation status in adult glioblastoma.

BACKGROUND AND PURPOSE: As a crucial diagnostic and prognostic biomarker, telomerase reverse transcriptase (TERT) promoter mutation holds immense significance for personalized treatment of patients with glioblastoma (GBM). In this study, we developed a radiomics nomogram to determine the TERT promoter mutation status and assessed its prognostic efficacy in GBM patients. METHODS: The study retrospectively included 145 GBM patients. A comprehensive set of 3736 radiomics features was extracted from preoperative magnetic resonance imaging, including T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1WI, and fluid-attenuated inversion recovery. The construction of the radiomics model was based on integrating the radiomics signature (rad-score)with clinical features. Receiver-operating characteristic curve analysis was employed to evaluate the discriminative ability of the prediction model, and the risk score was used to stratify patient outcomes. RESULTS: The least absolute shrinkage and selection operator classifier identified 10 robust features for constructing the prediction model, and the radiomics nomogram exhibited excellent performance in predicting TERT promoter mutation status, with area under the curve values of.906 (95% confidence interval [CI]:.850-.963) and.899 (95% CI:.708-.966) in the training and validation sets, respectively. The clinical utility of the radiomics nomogram is further supported by calibration curve and decision curve analyses. Additionally, the radiomics nomogram effectively stratified GBM patients with significantly different prognoses (HR = 1.767, p = .019). CONCLUSION: The radiomics nomogram holds promise as a modality for evaluating TERT promoter mutations and prognostic outcomes in patients with GBM.

Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study.

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

A novel combination of niraparib and anlotinib in platinum-resistant ovarian cancer: Efficacy and safety results from the phase II, multi-center ANNIE study.

Background: Patients with platinum-resistant recurrent ovarian cancer (PROC) face poor prognosis and limited treatment options. Single-agent antiangiogenics and poly (ADP-ribose) polymerase (PARP) inhibitors both show some activities in platinum-resistant diseases. The ANNIE study aimed to evaluate the efficacy and safety of the novel combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib in patients with PROC. Methods: ANNIE is a multicentre, single-arm, phase 2 study (ClinicalTrials.gov identifier NCT04376073) conducted at three hospitals in China. Eligible patients had histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal cancer that recurred within 6 months of last platinum-based chemotherapy. Patients with prior PARP inhibitor exposure were excluded. The enrolled patients received oral niraparib 200 mg or 300 mg (baseline body weight-directed) once daily continuously and anlotinib 10 mg (12 mg before protocol amendment) once daily on days 1-14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). Findings: Between May 22, 2020, and April 22, 2021, 40 patients were enrolled and treated. Thirty-six patients underwent post-baseline tumour assessments. By data cut-off (January 31, 2022), median follow-up was 15.4 months (95% CI 12.6-17.7). Intention-to-treat ORR was 50.0% (95% CI 33.8-66.2), including one complete response and 19 partial responses. Median (95% CI) progression-free survival and overall survival were 9.2 months (7.4-11.9) and 15.3 months (13.9-not evaluable), respectively. Drug-related, grade ≥3 TEAEs were reported in 26 (68%) patients. There were no treatment-related deaths. Interpretation: Niraparib plus anlotinib showed promising antitumour activity in patients with PROC. This oral combination warrants further investigation as a potential novel, convenient treatment option for patients with PROC. Funding: Zai Lab (Shanghai) Co., Ltd; Jiangsu Chia Tai-Tianqing Pharmaceutical Co., Ltd; the National Natural Science Foundation of China (No. 82102783).

The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes.

BACKGROUND: We investigate the correlation between programmed cell death-ligand 1 (PD-L1) and tumor-associated immune cell (TAIC) density in small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) and their correlation with clinicopathologic features. METHODS: PD-L1 and mismatch repair protein (MMR) expression in cancer cells and the density of TAIC were evaluated by immunohistochemistry in 89 SCNEC patients. The combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) of PD-L1 were measured, along with their correlation with clinicopathologic features in SCNEC patients using statistical analyses. RESULTS: CPS of PD-L1 ≥ 1 was seen in 68.5% of patients, positive TPS and ICS of PD-L1 were detected in 59.6% and 33.7% of patients, respectively. PD-L1CPS was higher in tumor-infiltrating immune cells (r = 0.387, p = 0.001) and positively correlated with programmed cell death-1 and forkhead box P3 + regulatory T cell (FOXP3 + Treg) infiltration (r = 0.443, p < 0.001; r = 0.532, p < 0.001). There was no statistical correlation between PD-L1 and MMR status. PD-L1CPS and PD-L1ICS positivity were independent prognostic factors, correlating with a favorable survival (HR (95%CI) = 0.363(0.139-0.950), p = 0.039 and HR (95% CI) = 0.199(0.050-0.802), p = 0.023, respectively). PD-L1ICS positivity was an independent indicator of recurrence in SCNEC patients and associated with better disease-free survival (HR (95% CI) = 0.124(0.036-0425), p = 0.001). TAIC and MMR levels had no statistical impact on survival results. CONCLUSIONS: PD-L1 positivity was seen in over half of SCNEC tumors. It may work synergistically with FOXP3 + Treg and other infiltrating immune cells to support an adaptive immune response. PD-L1 positivity may be a favorable prognostic factor in SCNEC.

The impact of lymph node dissection on survival in patients with clinical early-stage ovarian cancer.

OBJECTIVE: To estimate the impact of lymph node dissection on survival in patients with apparent early-stage epithelial ovarian cancer (EOC). METHODS: We conducted a retrospective review of patients with clinical stage I-II EOC. All patients underwent primary surgery at Sun Yat-sen University Cancer Center between January 2003 and December 2015. Demographic features and clinicopathological information as well as perioperative adverse events were investigated, and survival analyses were performed. RESULTS: A total of 400 ovarian cancer patients were enrolled, and patients were divided into 2 groups: 81 patients did not undergo lymph node resection (group A), and 319 patients underwent lymph node dissection (group B). In group B, the median number of removed nodes per patient was 25 (21 pelvic and 4 para-aortic nodes). In groups A and B, respectively, the 5-year progression-free survival (PFS) rates were 83.3% and 82.1% (p=0.305), and the 5-year overall survival (OS) rates were 93.1% and 90.9% (p=0.645). The recurrence rate in the retroperitoneal lymph nodes was not associated with lymph node dissection (p=0.121). The median operating time was markedly longer in group B than in group A (220 minutes vs. 155 minutes, p<0.001), and group B had a significantly higher incidence of lymph cysts at discharge (32.9% vs. 0.0%, p<0.001). CONCLUSION: In patients with early-stage ovarian cancer, lymph node dissection was not associated with a gain in OS or PFS and was associated with an increased incidence of perioperative adverse events.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.

Overexpression of YES1 is associated with favorable prognosis and increased platinum-sensitivity in patients with epithelial ovarian cancer.

AIMS: The prognostic application of YES1 in epithelial ovarian cancer (EOC) is currently unclear. We aimed to investigate the expression of YES1 and its correlation with survival outcome in patients with EOC. METHODS: A retrospective study of patients diagnosed with EOC at the Cancer Center, Sun Yat-Sen University, Guangzhou, China between 2002 and 2013 was conducted. The immunohistochemical expression of YES1 was assessed using tissue microarray. Survival rates were analyzed by the Kaplan-Meier method and were compared between groups using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: A total of 132 patients with EOC were enrolled. Patients in the YES1-high group exhibited significantly better OS and PFS, compared with those in the YES1-low group (P=0.02 and P=0.03, respectively). Further univariate and multivariate regression analyses indicated YES1 as an independent prognostic factor for the OS of patients with EOC. Notably, within the high YES1 expression group, 40 cases (74.1%) were of the platinum-sensitive group while 14 (25.9%) overlapped were of the platinum-resistant group. Conversely, in the low YES1 expression group, 11 cases (47.8%) were platinum-sensitive, and 12 (52.2%) platinum-resistant. Overall, patients within the high YES1 expression group were deemed significantly more sensitive to platinum-based chemotherapy than the low YES1 expression group (P=0.03), and YES1 levels were consistently and significantly higher in the platinum-sensitive group. CONCLUSIONS: High YES1 cytoplasmic expression in EOC patient tissue is significantly correlated with favorable prognosis. Patients with high YES1 expression tend to be sensitive to platinum-based chemotherapy.

Combined score of pretreatment platelet count and CA125 level (PLT-CA125) stratified prognosis in patients with FIGO stage IV epithelial ovarian cancer.

BACKGROUND: The majority of death-related ovarian cancer is epithelial ovarian cancer (EOC). Regarding the Federation of Gynecology and Obstetrics (FIGO) stage IV EOC, the 5-year overall survival (OS) has not changed in last decades. Platelet (PLT) count and CA125 level are both prognostic markers that related to inflammation and immune evasion in EOC. This study intended to assess the prognostic value of pretreatment PLT count and CA125 level in FIGO stage IV EOC. METHODS: The study included 108 patients diagnosed with FIGO stage IV EOC and treated with surgery and/or chemotherapy between January 1995 and December 2016. The PLT counts and CA125 levels of the patients before any treatment were analysed with clinical and pathological parameters, OS and progression-free survival (PFS). The survival of different groups was analyzed using the Kaplan-Meier method. The PLT-CA125 scores (0, 1, and 2) were defined basing on the presence of thrombocytosis (PLT count > 400,000/µL), an elevated CA125 level (CA125 > 1200 U/mL), or both. The prognostic value of PLT-CA125 was assessed with a Cox regression model. RESULTS: Median OS, but not median PFS, was significantly decreased in patients with thrombocytosis or elevated CA125 levels when compared with the others (p = 0.011 & p = 0.004). The median OS was significantly decreased in patients with a PLT-CA125 score of 2 [37.8 months; 95% confidence interval (CI) 20.6-54.9] compared with patients with a PLT-CA125 score of 0 (70.0 moths, 95% CI 38.0-101.9, p < 0.001). The median PFS was also significantly decreased in patients with a PLT-CA125 score of 2 (19.6 months; 95% CI 13.0-26.3) compared with patients with a PLT-CA125 score of 0 (32.0 months; 95% CI 23.3-40.7, p = 0.011). Furthermore, multivariate analysis identified both PLT-CA125 scores of 2 and 1 as independent poor prognostic factors for OS (p = 0.004 & p < 0.001) and PFS (p = 0.033 & p = 0.017) compared with a PLT-CA125 score of 0. CONCLUSIONS: The pretreatment PLT-CA125 score can be a reliable marker with high accessibility for stratifying prognosis in patients with FIGO stage IV EOC.

SPOCD1 promotes the proliferation and metastasis of glioma cells by up-regulating PTX3.

Gliomas are the most prevalent type of primary brain tumors in adults, accounting for more than 40% of neoplasms in the central nervous system. The spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been recently identified and found to discriminate progressive from non-progressive bladder cancers. In this study, we detected high-level of SPOCD1 expression in glioma and its high expression significantly associated with advanced tumor grade and poor prognosis. In vitro assays showed that knockdown of SPOCD1 significantly inhibited cell proliferation and colony formation capacities in U373 and U87 cells. In a xenograft model of glioma, SPOCD1 was also found to inhibit tumor growth. In addition, knockdown of SPOCD1 was shown to inhibit cell migration and invasion in glioma U373 and U87 cells. SPOCD1 positively regulated the expression of Pentraxin 3 (PTX3), whereas overexpression of PTX3 attenuated SPOCD1 knockdown-mediated inhibition of cell proliferation, migration and invasion in glioma cells. Our observations suggest that SPOCD1 promotes the proliferation and metastasis of glioma cells through regulating PTX3. Our data might provide novel evidence for the diagnosis and treatment of glioma in clinic.

The Role of GOLPH3L in the Prognosis and NACT response in Cervical Cancer.

Background: We previously reported GOLPH3L is a novel oncogene associated with ovarian cancer. The role of GOLPH3L in cervical cancer and its cellular functions has not been determined. This study investigated clinical significance of GOLPH3L and potential proteins and pathways associated with GOLPH3L in cervical squamous cell carcinoma. Methods: Immunohistochemistry and western blot were used to examine the expression of GOLPH3L in cervical squamous cell carcinoma tissue specimens and adjacent non-cancerous tissues. The clinical and prognostic significance of GOLPH3L expression was statistically analyzed. Cell proliferation rate, cell cycle progression, apoptosis and cisplatin response in GOLPH3L silenced SiHa and HeLa cells were also examined. Phospho-antibody array was used to identify changes in protein phosphorylation and the corresponding signaling pathways associated with these changes. Results: GOLPH3L overexpressed in cervical cancer tissue specimens compared with normal adjacent non-cancerous tissues. Increased GOLPH3L expression was associated with FIGO staging (P=0.033), cervical stromal invasion (P=0.037), cervical canal stromal invasion (P=0.027), lymph node metastasis (P=0.016) and positive surgical margins (P=0.015). Patients with lower expression of GOLPH3L demonstrated longer progression-free survival and overall survival compared with those with higher expression. The tissue samples from patients who poorly responded to neoadjuvant chemotherapy (NACT) exhibited increased GOLPH3L expression levels compared with tissue samples from patients who achieved a pathologic complete response (pCR). Patients with lower GOLPH3L expression level, poorer tumor differentiation, shorter NACT treatment intervals and smaller tumor sizes were more likely to achieve a pCR after NACT. Knockdown GOLPH3L in cells was associated with an induction of cell cycle arrest, increased apoptosis and cisplatin sensitivity, and a reduction in cellular viability. Phospho-antibody array suggested GOLPH3L plays a role in mediating cell cycle arrest. Conclusions: This study provides a potential biomarker for predicting prognosis and NACT response in patients with cervical squamous cell carcinoma. The functional role of GOLPH3L in cervical cancer merits further investigation.

Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice.

CONTEXT: Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection. OBJECTIVE: We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI). MATERIALS AND METHODS: BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks. RESULTS: WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1ß (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-ß1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration. DISCUSSION AND CONCLUSION: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.

Prognostic and Safety Roles in Laparoscopic Versus Abdominal Radical Hysterectomy in Cervical Cancer: A Meta-analysis.

OBJECTIVE: Studies comparing the prognostic results between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in cervical cancer reported contradictory results. We aimed to evaluate the prognostic and safety roles of LRH by pooling studies in a meta-analysis. MATERIALS AND METHODS: Original articles were searched in PubMed, EMBASE, and the Cochrane Library. The survival results (5-year disease-free survival [DFS], 5-year overall survival [OS], and recurrence rate [RR]), safety parameters (intra-, peri-, and postoperative complication rates and postoperative bowel or bladder recovery days), efficiency parameters (pelvic/para-aortic lymph nodes removed), and other parameters (operative time, estimated blood loss, and hospital of stay) between the two approaches were reviewed. RESULTS: For the 2922 cases identified, DFS, OS, and RR did not differ in balanced prognostic factors, including lymph node metastasis, Stage IIB or above, non-squamous cancer histology, grade G3, lymphovascular space invasion, tumor size ≥4 cm, and positive parametrial and vaginal margin rates. Meanwhile, LRH was associated with higher complication rates and a shorter time to the recovery of bowel or bladder function than for ARH. The number of removed pelvic or para-aortic lymph nodes did not significantly differ. Other parameters showed LRH was associated with a longer operative time, less blood loss, and a shorter length of hospital stay. The survival and prognostic results did not differ in balanced prognostic factors. CONCLUSIONS: LRH is safe and has lower operative complication rates than ARH.

Should the Optimal Adjuvant Treatment for Patients With Early-Stage Endometrial Cancer With High-Intermediate Risk Factors Depend on Tumor Grade?

OBJECTIVES: To explore whether the optimal adjuvant treatments for patients with early-stage endometrial cancer with high-intermediate risk (HIR) factors should depend on tumor grade. METHODS: A retrospective analysis of patients with HIR endometrial cancer from 1999 to 2012 was conducted. The adjuvant treatments and survival were evaluated. RESULTS: A total of 129 patients with HIR were identified, of which 71 had grade 1-2 tumor and 58 had grade 3 tumor. The adjuvant treatment chosen differed significantly between patients with grade 1-2 and grade 3 tumors (P < 0.001). Most of the patients (76.1%) with grade 1-2 tumors received no adjuvant treatment; however, chemotherapy alone was the most frequent (75.9%) adjuvant treatment for patients with grade 3 tumors. In the grade 1-2 group, no significant differences in the 5-year progression-free survival (94.1% vs 96.3%; P = 0.857) and overall survival (OS) rates (94.1% vs 98.1%; P = 0.401), respectively, were observed between patients who received adjuvant treatment (radiation and chemotherapy with or without radiation) and those who did not. For grade 3 disease, patients undergoing adjuvant chemotherapy alone had a favorable outcome with the 5-year progression-free survival rate of 84.4% and the OS rate of 95.5%. CONCLUSION: It is logical to speculate that surgery followed by observation might be sufficient for patients with HIR with grade 1-2 tumor. Further prospective trials are required to confirm the issue owing to the limited number of this population. More studies are warranted to clarify the feasibility and efficacy of adjuvant chemotherapy alone in patients with HIR with grade 3 tumor.

Low initial human papillomavirus viral load may indicate worse prognosis in patients with cervical carcinoma treated with surgery.

OBJECTIVE: To evaluate the prognostic implication of human papillomavirus (HPV) viral load in cervical cancer patients who underwent radical hysterectomy. METHODS: We conducted a retrospective review of patients with stage IA2 through stage IIIA cervical carcinoma who underwent radical hysterectomy at Sun Yat-sen University Cancer Center between January 2005 and December 2009. Patients who had undergone preoperative hybrid capture 2 testing to detect HPV DNA were included. A total of 346 patients positive for HPV DNA were enrolled and stratified into two groups according to the median HPV viral load. RESULTS: HPV viral load was significantly correlated with lymphovascular space invasion (p=0.026) and deep stromal invasion (p=0.024). However, other factors, such as age, stage, histologic grade, histologic type, lymph node metastasis, and tumor size, were not significantly associated with viral load. Low HPV viral load was correlated with poor disease-free survival in univariate analysis (p=0.037) and multivariate analysis (p=0.027). There was no significant difference in overall survival with regard to initial HPV viral load. CONCLUSION: Low initial HPV viral load may be a poor prognostic factor for cervical cancer patients who have undergone radical hysterectomy.

URG4 overexpression is correlated with cervical cancer progression and poor prognosis in patients with early-stage cervical cancer.

BACKGROUND: Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. However, the correlation between URG4 expression and clinicopathological significance in human cancer remains unclear. Therefore, this study investigated its expression and clinicopathological significance in cervical cancer patients. METHODS: URG4 expression was examined using quantitative PCR (qPCR) and western blotting in normal cervical epithelial cells, cervical cancer cells, and eight matched pairs of cervical cancer tissues and adjacent noncancerous tissues from the same patient. In addition, immunohistochemistry (IHC) was used to examine URG4 expression in paraffin-embedded tissues from 167 cervical cancer patients (FIGO stages Ib1-IIa2). Statistical analyses were performed to evaluate associations between URG4 expression and prognostic and diagnostic factors. RESULTS: URG4 was significantly upregulated in the cervical cancer cell lines and tissues compared with the normal cells and adjacent noncancerous cervical tissues. IHC revealed high URG4 expression in 59 out of the 167 (35.13%) cervical cancer specimens. Its expression was significantly correlated with clinical stage (P < 0.0001), tumour size (P = 0.012), T classification (P = 0.023), lymph node metastasis (P = 0.001) and vaginal involvement (P = 0.002). Patients with high URG4 expression, particularly those who received concurrent chemotherapy and radiotherapy (P < 0.0001), showed a shorter overall survival (OS) and disease-free survival (DFS) compared to those with the low expression of this protein. Multivariate analysis revealed that URG4 expression is an independent prognostic factor for cervical cancer patients. CONCLUSIONS: Our results demonstrated that elevated URG4 protein expression is associated with a poor outcome in patients with early-stage cervical cancer. URG4 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.

Clinical outcome of 31 patients with primary malignant melanoma of the vagina.

OBJECTIVE: To investigate the clinical characteristics of and prognostic factors for primary malignant melanoma of the vagina. METHODS: Clinical data from 31 patients treated for primary malignant melanoma of the vagina at the Sun Yat-sen University Cancer Center between March 1970 and June 2005 were retrospectively analyzed. RESULTS: The median age was 58 years (range, 18 to 73 years), and the main symptoms reported were vaginal bleeding and vaginal discharge. Most tumors were of the nodular type and classified as stage I according to International Federation of Gynecology and Obstetrics staging criteria. Surgery was performed on 22 patients, chemotherapy was administered to 7 patients, and immunotherapy was administered to 19 patients. Recurrent tumors developed in 11 patients (35.5%) during a median follow-up period of 20.2 months (range, 1 month to 18 years). The 5-year overall survival rate was 32.3%. Univariate analysis revealed that macroscopic tumor growth and the treatment method significantly affected survival outcome (p=0.039 and p<0.001, respectively), whereas the radicality of surgery did not (p=0.296). Multivariate analysis revealed that macroscopic tumor growth (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.4 to 12.1; p=0.010) and treatment method (HR, 0.3; 95% CI, 0.1 to 0.9; p=0.025) were independent prognostic factors for overall survival. CONCLUSION: Patients with primary vaginal melanoma have a poor prognosis. Macroscopic tumor growth and treatment method are prognostic factors for primary malignant melanoma of the vagina.

Elevated expression of iASPP correlates with poor prognosis and chemoresistance/radioresistance in FIGO Ib1-IIa squamous cell cervical cancer.

iASPP (inhibitory member of the ASPP family), the conserved key inhibitor of p53, is overexpressed and plays an important oncogenetic role in many human cancers. However, its function in cervical cancer remains unknown. The objective of this study was to investigate the expression and clinical relevance of iASPP in cervical cancer. The mRNA and protein expression levels of iASPP were determined by real-time quantitative reverse transcription with the polymerase chain reaction and Western blot. Paraffin sections of 149 patients with FIGO Ib1-IIa squamous cell cervical cancer were stained by using immunohistochemistry for iASPP, and its relationship with clinicopathologic parameters and prognosis of cervical cancer patients was analyzed. The mRNA and protein expression levels of iASPP were significantly elevated in cervical cancer tissues. The increased nuclear iASPP expression was correlated strongly with higher FIGO staging, deep cervical stromal invasion, pelvic lymph node metastasis, and poor overall and disease-free survival of patients with cervical cancer (all P<0.05). Multivariate Cox analysis showed that high nuclear iASPP expression was an independent prognostic factor for overall survival. Furthermore, patients with high nuclear iASPP expression were much more resistant to radiation or chemotherapy, resulting in poor overall and disease-free survival than those with low expression after receiving radiation or chemotherapy (all P<0.05) and indicating correlations with chemoresistance and radioresistance. This study thus demonstrates that iASPP is highly elevated in human cervical cancer, and that overexpression of nuclear iASPP is correlated with poor prognosis and chemoresistance/radioresistance, suggesting that iASPP might serve as a novel potential prognostic marker and therapeutic target for cervical cancer.

Screening and identification of biomarkers in ascites related to intrinsic chemoresistance of serous epithelial ovarian cancers.

OBJECTIVE: The ability to predict responses to chemotherapy for serous epithelial ovarian cancer (EOC) would be valuable since intrinsically chemoresistant EOC patients (persistent or recurrent disease within 6 months) gain little benefit from standard chemotherapy. The aim of this study was to screen and identify distinctive biomarkers in ascites of serous EOC associated with intrinsic chemoresistance. METHODS: Protein samples from ascites of 12 chemosensitive and 7 intrinsically chemoresistant serous EOC patients were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Furthermore, the identified proteins were validated by ELISA in ascites samples from 19 chemosensitive and 9 intrinsically chemoresistant EOC patients. RESULTS: The number of spots detected in all 2-D DIGE gels ranged from 1523-1711 using DeCyder software analysis. Thirty-four spots were differentially expressed based on the criteria of an average ratio of more than 1.5 and a student t-test P value <0.05. After MALDI-TOF/TOF MS analysis, 11 differentially expressed proteins, including 3 up-regulated and 8 down-regulated proteins, in ascites of chemoresistant tumors were successfully identified. Of the four selected proteins (ceruloplasmin, apoliprotein A-IV, transthyretin and haptoglobin) in ascites tested by ELISA, only ceruloplasmin was present at significantly different levels between the chemoresistant and chemosensitive ascites samples with average concentrations of 192.2 µg/ml and 157.5 µg/ml, respectively (P = 0.001). CONCLUSION: The significantly up-regulated level of ceruloplasmin in the ascites fluid of intrinsic chemoresistant serous EOC patients suggests its potential as a prognostic biomarker for responses to chemotherapy. This finding prompts further investigation with a larger study in order to validate the clinical utility of ceruloplasmin.

[Interstitial implantation of ¹²5I seed therapy for recurrent ovarian cancer].

OBJECTIVE: To explore the feasibility, short-term efficacies and complications of computed tomography (CT)-guided ¹²5I interstitial implant therapy for recurrent ovarian cancer. METHODS: From October 2009 to November 2010, a total of 25 lesions for 12 patients were diagnosed as recurrent ovarian cancer by positron emission tomography/computed tomography (PET/CT). Among 25 lesions, 21 underwent ¹²5I seed implantation. And 4 lesions of liver and spleen in one patient were treated with microwave ablation. Nine patients underwent 2 - 6 cycles of chemotherapy after seeding. There were 11 lesions with diameter > 2 cm and 10 ≤ 2 cm. According to the area of physiologic 18FDG uptake in lesions, the treatment plans were formulated by computerized treatment planning system (TPS) and Memorial Sloan-Ketterin nomograph. The matched peripheral dose (MPD) was 145 Gy in target mass. A median of 20.5 seeds per patient (range: 9 - 45) were implanted. The efficacies were evaluated by CT and 18F-FDG PET/CT findings. RESULTS: One patient died of renal failure while the other patients survived during a median follow-up of 15 mouths (range: 9 - 19). Ten lesions showed complete remission, 6 partial remission and 5 progressive disease. The effective rate was 76.2% (16/21). Compared with those > 2 cm, the lesions ≤ 2 cm in diameter had a better local control rate by Fisher's exact test (P = 0.035). The hepatic and renal lesions treated by microwave ablation showed inactivation on PET/CT. Only one patient suffered from sciatic nerve injury caused by punctuation and numbness and pain of right lower extremity were persistent. There was no onset of the complications of radiation injury, such as intestinal fistula and proctitis. CONCLUSION: The CT-guided ¹²5I interstitial implant therapy for recurrent ovarian cancer yields excellent short-term efficacies with fewer complications. The combined modality of ¹²5I interstitial implant and chemotherapy may further improve the patient outcomes.

[Treatment and prognostic analysis of ovarian cancer patients with isolated region of lymph node recurrence].

OBJECTIVE: To evaluate the management and survival of lymph node region recurrence of epithelial ovarian cancer (EOC), and discuss its suitable therapeutic strategy. METHODS: Thirty-eight patients with the recurrence of lymph node region were extracted from 1945 patients who were diagnosed EOC and treated in Sun Yat-sen University Cancer Center from January 1995 to December 2008. The clinical characteristics, therapy methods and survival of them were retrospectively analyzed. Patient age at initial diagnosis was > 50 years old in 24 patients and ≤ 50 years old in 14 patients. There were 15 cases with stage II and 23 cases with stage III in terms of initial International Federation of Gynecology and Obstetrics (FIGO, 1987) staging. Classified with histological grade, 7 cases were in G(1), 14 cases were in G(2), 17 cases were in G(3); according to the histological types, 19 cases were with serous adenocarcinomas, and 19 cases were with non-serous adenocarcinomas (including 9 endometrioid adenocarcinoma, 1 mucinous adenocarcinoma and 9 unclassified adenocarcinoma). The median follow-up time was 59 months (ranged 16 to 124 months). RESULTS: (1) Feature of recurrences: the median interval of last treatment to recurrence was 18 months (range 9 to 96 months). Most of them were absence of symptoms. The serum level of CA(125) was elevated in 15 patients (39%, 15/38). (2) Treatment of recurrences:of the 38 patients, 19 underwent lymphadnectomy for recurrence regions and received adjuvant chemotherapy (surgery + chemotherapy group), 14 received local radiotherapy and adjuvant chemotherapy (radiotherapy + chemotherapy group), 5 received chemoherapy only (chemotherapy group). There were 35 cases achieved complete response (CR), including 19 patients underwent secondary debulking surgery in surgery + chemotherapy group, 14 cases in radiotherapy + chemotherapy group (12 of them treated by radiotherapy, the other 2 cases reached CR after adjuvant chemotherapy) and 2 cases in chemotherapy group. While only 3 patients reached partial response in chemotherapy group. (3) Survival and second recurrences: during follow-up, 14 cases died of tumor, 4 cases survival with tumor while 20 cases survival without evidence of tumor. The 5-year post-recurrence survival rate of 38 cases was 66.5%, with 71.8%, 68.8% and 40.0% in surgery + chemotherapy, radiotherapy + chemotherapy, and chemotherapy group, respectively, and there was no significant difference in survival rate between them (P > 0.05). A total of 15 patients experienced second recurrences, including 7 cases with peritoneal and 8 cases with lymph node region recurrences. (4) Prognosis factors: the univariate analysis shown that survival after recurrence was significantly related to patient age, tumor-free interval and number of recurrence disease (P < 0.05), while not to FIGO stage, histological type, histological grade, and lymphadnectomy during primary surgery (P > 0.05). The multivariate analysis showed that patient age and tumor-free interval were independent prognostic variables for survival after recurrence (P < 0.05). CONCLUSIONS: The lymph node region recurrence of EOC may be have good prognosis and distinctive clinical process. Local treatment strategies including secondary surgery and radiotherapy should be considered, which may significantly improve survival in ovarian cancer patients with lymph node region recurrence.