Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Application of NGS molecular classification in the diagnosis of endometrial carcinoma: A supplement to traditional pathological diagnosis.

OBJECTIVE: This study aims to demonstrate the advantages of NGS molecular classification in EC diagnosis and to assess whether molecular classification could be performed on curettage specimens and its concordance with subsequent hysterectomy specimens. METHODS: 80 patients with hysterectomy specimens and 35/80 patients with paired curettage specimens were stratified as POLE mut, MSI-H, TP53 wt, or TP53 abn group by NGS panel. Histotype, tumor grade, IHC results, and other pathological details were taken from original pathological reports. RESULTS: The correlation analysis of 80 patients with hysterectomy specimens between NGS molecular classification and clinicopathological characters displayed that the POLE mut group was associated with EEC (87.5%) and TP53 abn subtype was correlated to a later stage (Stage II-IV, 47.6%), G3 (76.2%), serous histology (61.9%) and myometrial invasion ≥50% (47.6%). A favorable concordance (31/32, 96.9%) was shown in MSI analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 81.5% (53/65). Compared with the p53 IHC abnormal group, the TP53 mutation group had a higher correlation with high-risk factors. A high level of concordance (31/35, 88.0%) of NGS molecular classification was achieved between curettage specimens and hysterectomy specimens while grade and histotype (including unclassified group) from curettage specimens and hysterectomy specimens showed only moderate levels of agreement, 54.3% (19/35) and 68.6% (24/35), respectively. CONCLUSION: NGS molecular classification achieved on curettage samples showed high concordance with the final hysterectomy specimens, demonstrating superior to the conventional pathological assessment of grade and histotype and potential utilization in clinical practice.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Deep learning magnetic resonance imaging predicts platinum sensitivity in patients with epithelial ovarian cancer.

Objective: The aim of the study is to develop and validate a deep learning model to predict the platinum sensitivity of patients with epithelial ovarian cancer (EOC) based on contrast-enhanced magnetic resonance imaging (MRI). Methods: In this retrospective study, 93 patients with EOC who received platinum-based chemotherapy (≥4 cycles) and debulking surgery at the Sun Yat-sen Memorial Hospital from January 2011 to January 2020 were enrolled and randomly assigned to the training and validation cohorts (2:1). Two different models were built based on either the primary tumor or whole volume of the abdomen as the volume of interest (VOI) within the same cohorts, and then a pre-trained convolutional neural network Med3D (Resnet 10 version) was transferred to automatically extract 1,024 features from two MRI sequences (CE-T1WI and T2WI) of each patient to predict platinum sensitivity. The performance of the two models was compared. Results: A total of 93 women (mean age, 50.5 years ± 10.5 [standard deviation]) were evaluated (62 in the training cohort and 31 in the validation cohort). The AUCs of the whole abdomen model were 0.97 and 0.98 for the training and validation cohorts, respectively, which was better than the primary tumor model (AUCs of 0.88 and 0.81 in the training and validation cohorts, respectively). In k-fold cross-validation and stratified analysis, the whole abdomen model maintained a stable performance, and the decision function value generated by the model was a prognostic indicator that successfully discriminates high- and low-risk recurrence patients. Conclusion: The non-manually segmented whole-abdomen deep learning model based on MRI exhibited satisfactory predictive performance for platinum sensitivity and may assist gynecologists in making optimal treatment decisions.

Efficacy of neoadjuvant hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer (the NHIPEC trial): study protocol for a randomised controlled trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone. METHODS: This study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60-75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events. ETHICS APPROVAL AND DISSEMINATION: This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital (approval number: 2020-ky-050). Results will be submitted to peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000038173.

Pembrolizumab in FIGO IVB Verrucous Carcinoma of the Vulva: A Case Report.

BACKGROUND: Vulvar cancer is the fourth most common gynecologic cancer, and prognosis is poor in advanced vulvar cancer patients. Treatment for advanced vulvar cancer has not been satisfactory. In this report, we firstly report a FIGO IVB vulva verrucous carcinoma patient who obtained good prognosis after systemic treatment. CASE PRESENTATION: A patient was admitted to hospital due to her vulvar lesion persistent for past 14 years. The vulvar mass has widely invaded urethra, part of anus, the lower third of the vagina, bilateral superior and inferior branches of pubis, and bilateral internal and external muscles of obturator. Multiple metastatic lymph nodes were also found in the pelvic cavity. The histopathological studies confirmed vulvar verrucous carcinoma with a PD-L1 overexpression. After six courses of neoadjuvant chemotherapy and pembrolizumab, the patient underwent radical vulvectomy and achieved optimal cytoreduction. Postoperative pathology found no residual tumor. The patient then received one course of postoperative chemotherapy and pembrolizumab, underwent radiation therapy, and was disease free after 6 months follow-up. CONCLUSION: Our individualized treatment strategy is successful. Pembrolizumab is safe and effective in the treatment of advanced vulvar verrucous carcinoma with PD-L1 overexpression.

HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer.

PURPOSE: The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined. METHODS: We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored. RESULTS: Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025-0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells. CONCLUSION: HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.

Use of Laparoscopic Slip Knot with Purse-String Suture in Surgical Management of Unruptured Heterotopic Interstitial Pregnancies.

BACKGROUND The aim of this study was to investigate the advantages and disadvantages of using laparoscopic slip knot with purse-string suture technique in the surgical management of unruptured heterotopic interstitial pregnancies compared with other surgical strategies. MATERIAL AND METHODS We retrospectively analyzed data on 13 patients with unruptured heterotopic interstitial pregnancies who underwent laparoscopy in our hospital between May 2012 and August 2018. The control group consisted of 10 patients who underwent cornual resection or cornuostomy with conventional sutures and knots. The study group consisted of 3 patients whose surgical plans involved use of the slip knot with purse-string suture technique followed by cornuostomy. We evaluated the surgical records and video to comparatively analyze their operation duration, intraoperative blood loss, and pregnancy outcomes. RESULTS The average volume of intraoperative blood loss was 76.67±25 ml in the study group and 215.00±110 ml in the control group. On average, the intraoperative blood loss volume in the study group was 138 ml less than in the control group and the difference was statistically significant (P<0.05). There was no statistically significant difference in the live birth rate and operation time between the 2 groups (P>0.05). The duration of hemostasis in the study group was 11 min shorter than in the control group, while the duration of cornual electrocoagulation in the study group was 18.5 s shorter. Both groups achieved thorough hemostasis without the help of vasopressin and avoided use of embryo-killing drugs such as methotrexate. Neither group required second surgery or developed postoperative complications such as uterus rupture or persistent ectopic pregnancy. CONCLUSIONS This strategy is safe and reliable for gestational sac clearance while simultaneously preventing any potential harm to the intrauterine embryo. It is particularly suitable for unruptured HIP patients who have a strong desire to preserve their intrauterine embryos.

Diagnostic Value of Assessment of Cervical Involvement in Early-Stage Endometrial Adenocarcinoma: Comparison of Magnetic Resonance Imaging (MRI) Versus Hysteroscopy.

BACKGROUND The aim of this study was to compare magnetic resonance imaging (MRI) and hysteroscopy (HS) for assessing cervical involvement in early-stage endometrial adenocarcinoma in order to establish a more reliable screening method to aid in clinical decision-making. MATERIAL AND METHODS A retrospective analysis was performed on the clinicopathological data from 88 patients with stage I or II endometrial adenocarcinoma who underwent MRI and HS prior to surgery in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Chi-square and Fisher's exact tests were performed to compare the accuracy, sensitivity, specificity, and positive and negative predictive values in the diagnosis of cervical involvement by MRI and HS. The relationship between clinicopathological factors and the deviation of diagnosis by MRI and HS from that by pathology was also analyzed. RESULTS The accuracy of assessing cervical conditions was 93.2% by MRI and 55.7% by HS. Among these variables, the accuracy, specificity, and positive predictive values of MRI were significantly different from those of HS, while the sensitivity and negative predictive values of MRI and HS were not significantly different from each other. Age, tumor size, tumor differentiation, and depth of myometrial invasion were not associated with the differences in cervical assessment between MRI and HS. However, the tumor location may affect assessment by HS. CONCLUSIONS MRI is better than HS for cervical assessment. The negative predictive values of both MRI and HS are high and unsatisfactory.

Let-7g affects cell proliferation, migration and invasion in cervical squamous cell carcinomas via targeting collagen I.

Cervical cancer is one of the most common types of malignant gynecological tumors worldwide. Let-7g and collagen I have been reported to be involved in the occurrence and development of various cancers, but the clinical significance and biological function of these proteins in cervical squamous cell carcinoma (CSCC) have not been reported. Therefore, this study aimed to determine the underlying roles of let-7g and collagen I in CSCC. Tissue chip, qRT-PCR and western blot assays were used to examine the expression of collagen I in CSCC patients. A dual-luciferase reporter system was used to demonstrate the interaction between let-7g and collagen I. CCK8 and Transwell assays were applied to examine the effects of let-7g and collagen I on cell proliferation, migration and invasion. The results showed that collagen I was obviously increased in CSCC patients. Moreover, it was confirmed that collagen I is the direct target of let-7g. Gain- and loss-of-function experiments, for let-7g and collagen I indicated that let-7g obviously inhibited the proliferation, migration and invasion abilities of CSCC by regulating collagen I. Collectively, these data suggest that let-7g suppresses tumor growth and metastasis by targeting collagen I; therefore, let-7g and collagen I can be considered novel potential therapeutic targets for CSCC.

Treatment Approach and Prognosis of Pediatric and Adolescent Nonepithelial Malignant Ovarian Tumors: A Retrospective Prognosis Analysis.

STUDY OBJECTIVE: Nonepithelial malignant ovarian tumors are rare in the pediatric and adolescent population. The aim of this study was to observe the spectrum of pathology, presentation, outcome, and risk factors for survival of pediatric nonepithelial malignant ovarian tumors in a Chinese pediatric population. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a retrospective study of 171 girls (median age at presentation of 14 years) diagnosed with primary malignant ovarian tumors between 1990 and 2014 at the Yat-Sen Memorial Hospital and Cancer Center of Sun Yat-sen University. Symptoms, pathological data, treatments, and outcomes were obtained retrospectively from the medical records. RESULTS: Most (85.96%, 147/171) tumors occurred in patients aged 10-18 years and most cases were International Federation of Gynecology and Obstetrics stage I (68.42%, 117/171). The predominant pathological type was germ cell tumors (87.13%, 149/171). All patients underwent surgery, and 87 (50.88%, 87/171) underwent conservative incomplete staging surgery (unilateral salpingo-oophorectomy or tumor excision). The 5-year progression-free survival (PFS) was 59.2%. The 5-year overall survival (OS) was 88.7%. Surgical hospital (hazard ratio, 0.388; 95% confidence interval, 0.213-0.706; P = .002) was independently associated with PFS. Recurrence state (hazard ratio, 163.26; 95% confidence interval, 1.321-20,181.875; P = .038) was independently associated with OS. CONCLUSION: Ovarian cancers in children and adolescents have features of good prognosis. Girls who received their first surgery in a tertiary hospital had better PFS. Patients who did not suffer recurrence had better OS.

Detection of circulating tumour cells in patients with epithelial ovarian cancer by a microfluidic system.

Ovarian cancer is a gynaecological cancer with a high mortality rate. In recent years, circulating tumour cells (CTCs) have attracted attention from scientists because of their significant association with metastasis. However, due to the low CTC enrichment rate of the conventional CellSearch system and limited clinical sample sizes, only a small number of studies have focused on CTCs and epithelial ovarian cancer (EOC). Here, we apply a microfluidic system with immunomagnetic beads preconjugated with an anti-EpCAM antibody to enrich CTCs from whole blood and then analyse the enriched cells by immunofluorescence staining and automatic fluorescence microscope scanning. The average recovery rate of SK-OV-3 EOC cells was 70.2%±13.3%. When using blood samples from EOC patients and healthy volunteers, CTC counts of more than 8 cells were detected in 20 of 23 EOC patients (87.0%) but in none of the 16 healthy volunteers (0%). Total CTC counts were found to be significantly (P<0.05) elevated in the EOC group (median =55.0 [29.5, 123.0] CTCs/7.5 mL) compared with the healthy control group (median =0.5 [0,3.5] CTCs/7.5 mL). In conclusion, this is the first study to use the IsoFlux system on ovarian cancer samples. This system can efficiently capture EOC CTCs from a majority of patients and may provide a potential tool for further biological studies and for the development of in vitro EOC diagnostic products.

Impact of Hyperglycemia on Outcomes among Patients Receiving Neoadjuvant Chemotherapy for Bulky Early Stage Cervical Cancer.

BACKGROUND: The impact of hyperglycemia on survival of patients undergoing neoadjuvant chemotherapy (NACT) for bulky early stage cervical cancer (BESCC) has not been explored. METHOD: Records of patients who received NACT and radical hysterectomy in our institution between January 2005 and June 2010 were reviewed. RESULTS: In total, 347 patients were included. The median follow-up time was 37 months (range: 4-65). Patients with hyperglycemia (fasting blood glucose ≥ 100 mg/dl) had shorter recurrence-free survival (RFS) (univariate hazard ratio [HR] = 1.95, 95% confidence interval [CI] [1.16, 3.28], P = 0.010) and cancer-specific survival (CSS) (univariate HR = 2.24, 95% CI [1.33, 3.78], P = 0.002) compared with those with euglycemia (fasting blood glucose <100 mg/dl). In multivariate analysis, positive surgical margins, parametrium invasion, node metastasis, hyperglycemia and complete response to NACT independently predicted recurrence and cancer-specific death. To further validate the prognostic value of hyperglycemia, we conducted a subgroup analysis based on patient baseline characteristics and prognostic effect of hyperglycemia remained significant in all subgroups. On multivariable logistic regression analysis, euglycemia before NACT, squamous cell tumor and pre-treatment squamous cell carcinoma antigen levels < 3.5 ng/ml were identified as independent predictors of complete response after NACT. CONCLUSIONS: FBG ≥100 mg/dl is a negative prognostic predictor for cervical cancer patients receiving NACT for BESCC. Patients with hyperglycemia are less likely to achieve complete response after NACT. Our findings underscore the clinical utility of hyperglycemia screening of for cervical cancer patients.

Impact of the care provided by gynecologic oncologists on outcomes of cervical cancer patients treated with radical hysterectomy.

For many malignant diseases, specialized care has been reported to be associated with better outcomes. The purpose of this study is to investigate the influence of gynecologic oncologists on treatment outcomes for cervical cancer patients treated by radical hysterectomy. Records of patients who received radical hysterectomy between January 2005 and June 2010 were reviewed. Perioperative morbidity, recurrence-free survival, and cancer-specific survival were assessed. Cox regression model was used to evaluate gynecologic oncologists as an independent predictor of survival. A total of 839 patients were included. Of these patients, 553 were treated by gynecologic oncologists, while 286 were treated by other subspecialties. With regard to operative outcomes, significant differences in favor of operation by gynecologic oncologists were found in number of patients receiving para-aortic node sampling and dissection (P=0.038), compliance with surgical guidelines (P=0.003), operative time (P<0.0001), estimated blood loss (P<0.0001), transfusion rate (P=0.046), number of removed nodes (P=0.033), and incidences of ureteric injury (P=0.027), cystotomy (P=0.038), and fistula formation (P=0.002). Patients who were operated on by gynecologic oncologists had longer recurrence-free survival (P=0.001; hazard ratio [HR] =0.64; 95% confidence interval [CI] [0.48, 0.84]) and cancer-specific survival (P=0.005; HR=0.64; 95% CI [0.47, 0.87]), and this association remained significant in patients with locally advanced disease. Care by gynecologic oncologists was an independent predictor for improved recurrence-free survival (P<0.0001; HR=0.57; 95% CI [0.42, 0.76]) and cancer-specific survival (P=0.001; HR=0.58; 95% CI [0.42, 0.81]), which was still significant among patients with locally advanced cancer. Given the results, we believe for cervical cancer patients receiving radical hysterectomy, operation by gynecologic oncologists results in significantly improved surgical and survival outcomes. The importance of the subspecialty of a gynecologist for cervical cancer patients should be addressed in clinical practice, especially for those in developing countries.

Expression and functional role of ALDH1 in cervical carcinoma cells.

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.

The expression of ALDH1 in cervical carcinoma.

BACKGROUND: ALDH1 has been shown to play a role in the early differentiation of stem cells in some human malignancies. Whether cancer stem cells occur in ALDH1-associated cervical cancer is not known. MATERIAL/METHODS: We tested the hypothesis that cervical carcinomas contain subpopulations of cells that express ALDH1.The following sources of cervical carcinoma tissues were examined for the presence of stem cell marker ALDH1 by immunohistochemistry. Flow cytometric isolation of cancer cells was based on enzymatic activity of ALDH (Aldefluor assay). The mRNA and protein levels of ALDH1 were investigated by qRT-PCR and Western blot, respectively. We also detected the expression of CD133 identified as a stem cell marker for several cancers. RESULTS: 23/89 samples of invasive squamous carcinoma and 4/20 samples of adenocarcinomas exhibited immunoreactivity to stem cell marker aldehyde dehydrogenase 1 (ALDH1). Expression of ALDH1 was found in 24.77% of the samples. Flow cytometric analysis, qRT-PCR and Western blot also confirmed the presence of small subpopulations of ALDH1-positive cells. In contrast, we found cervical carcinoma had low CD133 population. CONCLUSIONS: Cervical carcinoma contains a small subpopulation of cells that may relate to a cancer stem cell-like phenotype, ALDH1.

Neoadjuvant chemotherapy with paclitaxel plus platinum for invasive cervical cancer in pregnancy: two case report and literature review.

BACKGROUND: Cervical cancer (including carcinoma in situ) is the most common malignancy during pregnancy. Neoadjuvant chemotherapy (NACT) with paclitaxel plus cisplatin has been used in patients with cervical cancer successfully, but experience of its prenatal treatment is limited. CASE REPORT: We report two pregnant women with locally advanced cervical cancer. They were treated with cisplatin plus paclitaxel NACT until fetal pulmonary maturity was achieved, and then accepted cesarean section followed by radical hysterectomy. To minimize the chemo-resistant/radio-resistant tumor cell clones and increase the potencies of NACT, we modified the dose of the chemotherapeutic agents and the treatment interval using cisplatin (50 mg/m(2)) and paclitaxel (75 mg/m(2)) every 2 weeks. Evaluation for clinical response to chemotherapy displayed a partial and complete response, respectively. Both patients had not had any evidence of recurrence for 21 and 13 months. Their children did not have any evidence of malformations and showed normal development at 21 and 13 months of follow-up, respectively. CONCLUSION: Neoadjuvant chemotherapy with paclitaxel plus cisplatin appears to be feasible and safe for pregnant patients with invasive cervical cancer and infants.

[Influences of lymphatic vessel ligation in pelvic lymphadenectomy on postoperative lymphocyst formation--a randomized controlled trial].

BACKGROUND AND OBJECTIVE: Pelvic lymphocysts are the most common postoperative complications of pelvic lymphadenectomy. Prevention of this disease is more important than treatment. This randomized study was to evaluate the preventive effect of lymph vessel ligation during pelvic lymphadenectomy on pelvic lymphocyst formation. METHODS: A total of 39 patients with gynecologic malignancy, who had pelvic lymphadenectomy in the Second Affiliated Hospital of Sun Yat-sen University from July 2006 to January 2007, were randomized into the ligation group (19 patients) and the non-ligation group (20 patients). All patients had no heart disease, hepatopathy, nephronia, pneumonopathy, hypoproteinemia and no history of radiotherapy. All the patients were followed-up with sonographic evaluation and physical examination for lymphocysts and other postoperative complications at 1, 4, 12, and 24 weeks after operation. RESULTS: No significant differences were observed between the two groups in pathlogic type, age, height, weight, body surface area, body mass index (BMI), operation duration, estimated blood loss, time to the passage of flatus, total drainage volume, duration of drainage, and duration of hospital stay (P>0.05). The occurrence rate of lymphocysts was significantly lower in the ligation group than in the non-ligation group at one week after operation (26.3% vs. 60.0%, P<0.05). The rates were slightly lower in the ligation group than in the non-ligation group without significant differences after then (31.6% vs. 55.0% at the 4th week), (16.7% vs. 45.0% at the 12th week), (20.0% vs. 27.8% at the 24th week). No significant differences were observed in the occurrence of other postoperative complications between the two groups (P<0.05). CONCLUSION: Ligations of the deep inguinal lymph vessels, obturator lymph vessels, common iliac lymph vessels, and the lymph vessels at the crossing of the external iliac and the inter iliac vein can decrease the occurrence of postoperative lymphocysts in short-term period, and will not increase the occurrence of postoperative complications.

[Primary clear cell carcinoma of the cervix: report of five cases and review of the literature].

OBJECTIVE: To explore the clinical diagnostic and therapeutic characteristics, prognostic factors of patients with primary clear cell carcinoma of the cervix. METHODS: The clinical, pathologic and follow-up data of patients with primary clear cell carcinoma of the cervix treated in our hospital from Jan 2003 to Dec 2006 were collected and analyzed retrospectively. The relative literature was reviewed. RESULTS: Five patients with primary clear cell carcinoma of the cervix were treated (1 case stage I b1, 2 of stage I b2, 1 of stage IIa, 1 of stage IVa). The mean age was 40.2 years (32 to 50 years). The primary symptom was mostly irregularly vaginal bleeding (3/5) and clinical type was predominantly (4/5) endophytic growth. The positive rate of cervical cytologic examination was 2/4, the negative rate of cervical human papillomavirus (HPV) DNA examination was 4/4. Serum CA125 level was abnormal (62.5 to 592.1 kU/L) before operation and when relapse occurred, and returned to normal after operation. All of five patients underwent operation, pathologic examination showed that three patients with infiltration in deep 1/2 myometrium of cervix, and two patients with infiltration in cervix-corpus juncture. Four patients underwent radical abdominal hysterectomy with systematic pelvic lymphadenectomy. All of four patients underwent four courses of chemotherapy with fluorouracil (5-FU) and carboplatin, one patient (stage II a) was added with intracavitary brachytherapy. None of the four patients had relapse or metastasis after a follow-up of 10 to 44 months. The patient with stage IV a underwent firstly hysterectomy and prerectum mass removal. Pelvic relapse occurred three months after operation and the patient then underwent the second operation, external beam radiotherapy and intracavitary brachytherapy and 8 courses of chemotherapy with paclitaxel (taxol) and carboplatin. There was no relapse or metastasis after a follow-up of 26 months. CONCLUSIONS: Primary clear cell carcinoma of the cervix may be unrelated to HPV infection. It shows predominantly endophytic growth and tends toward deep infiltration in cervix and extending to uterine corpus. Operation combined with chemotherapy with carboplatin and 5-FU or taxol may lead to relatively perfect short-term therapeutical effect. Serum CA125 can help to monitor prognosis.

[Construction of adeno-associated virus vector containing human papilloma virus 16 E7 gene and its expression in eukaryotic cells].

OBJECTIVE: To construct recombinant adeno-associated virus vector containing human papilloma virus (HPV) 16E7 gene and identify its effectiveness of expression in eukaryotic cell. METHODS: Recombinant adeno-associated virus particles containing HPV16E7 gene were generated by co-transfection of plasmids pAAV-MCS-E7, pAAV-RC and pAAV-helper into HEK293 cells. The viral particles were collected and purified. The vector titer was measured by southern blot. After the eukaryotic cells were transfected by virus particles, RT-PCR and western blot analysis were performed to identify rAAV expression. RESULTS: The recombinant adeno-associated virus vector containing HPV16E7 gene was correctly constructed. The vector titer measured by southern blot was approximately 1 x 10(11)/ml. After the eukaryotic cells were transfected by the recombinant adeno-associated virus vector, the expression of HPV16E7 gene was identified by RT-PCR and western blot. CONCLUSIONS: Recombinant adeno-associated virus HPV16E7 vector is successfully constructed and can stably express in eukaryotic cells.