| Part1. Abdominal Radical Trachelectomy for Cervical Malignancies1.1Abdominal radical trachelectomy (ART) for cervical cancer: how many patients may be eligible for fertility preservation?Objective:To determine the percentage of patients with early-stage cervical cancer who may be eligible for fertility preservation with abdominal radical trachelectomy (ART).Methods:We retrospectively reviewed the records of patients who underwent a radical hysterectomy for invasive cervical cancer at our institution from01/2000to12/2007, before ART was widely conducted at Cancer Hospital of Fudan University. Institutional eligibility criteria for ART were applied.Results:We identified3220patients who had undergone radical hysterectomy for cervical cancer;1638were age≤45at surgery. Six hundred and fifty-three (39.87%) patients may have been eligible by FIGO stage, tumor size and histology. In49patients, ART may have been aborted or altered because of unfavorable pathological factors. Six hundred and four (36.87%) patients were identified as eligible for ART in our study.Conclusion:A significant number of patients≤45with early-stage cervical cancer may be pathologically eligible for ART and should be counseled on this preoperatively. 1.2Abdominal radical trachelectomy for cervical malignancies: surgical, oncological and fertility outcomes in107patientsObjective:To report our experience of radical abdominal trachelectomy for patients with cervical malignancies.Methods:We conducted a retrospective review of a prospectively maintained database of patients undergoing fertility-sparing radical abdominal trachelectomy for cervical malignancies at our institution from04/2004to03/2012.Results:One hundred and seven patients with cervical malignancies underwent laparotomy for planned radical abdominal trachelectomy. Three patients needed immediate completion of radical hysterectomy due to unfavorable intraoperative findings. Median age was28.3years (range,11-42). Histology included11(10.58%) with adenocarcinoma,83(79.81%) with squamous carcinoma,4(3.85%) with adenosquamous carcinoma and6(5.77%) with botryoid sarcoma. Median number of nodes evaluated was25(range,12-53); Eighteen(17.31%) patients with pathologic risk factors received adjuvant therapy. Twenty-six of66IB1cases had tumor size>2cm. One recurrence was observed at a median follow-up of26.2months (range,0.5-94months). The recurrent case was a patient with2cm IB1squamous carcinoma. Frozen section evaluation for pelvic lymph nodes was negtive during the operation. However, final pathological results revealed one positive lymph node in right pelvis and the tumor was deep myometrial invasion and lymphvascular space invasion. The patient refused radiation and underwent four cycles of adjuvant chemotherapy. Five months after radical abdominal trachelectomy, upper abdominal CT scan revealed mutiple recurrent nodals in her liver. Five(4.81%) patients developed postoperative cervical stenosis-all occurred before we started to routinely install T-IUDs during the procedure. Only48patients completed the survey which aimed to understand what factors influenced these patients’reproductive outcomes. For various reasons, only12patients attempted to conceive and4of them succeeded (1employed assisted reproductive techniques). Three of them delivered by cesarean section after39weeks and one patient is currently pregnant.Conclusion:Radical abdominal trachelectomy seems to be a reasonable option for selected patients whose tumors are no larger than4cm when conducted by experienced gynecologic oncologists. The main perioperative complication is postoperative cervical stenosis, which could be effectively prevented by installation of a tailed T-IUD during the surgery. Social, familial and physical factors can largely influence the patients’ reproductive outcomes. The issues of reproductive concerns and quality of life require further investigation. 1.3Fertility-sparing surgery for pediatric (adolescent) patients with botryoid rhabdomyosarcoma involving the uterine cervixBackground:Botryoid rhabdomyosarcoma of the uterine cervix, which is most often seen arising in the adolescents, is extremely rare. In the past, this tumor was best treated with pelvic exenteration and chemoradiation.Objective:To report our experience on fertility-sparing treatment with this disease. To discuss proper selective criteria and type of surgery for fertility-sparing treatment with this disease.Methods:We conducted a retrospective review of a prospectively maintained database of patients undergoing fertility-sparing surgery for cervical botryoid rhabdomyosarcoma at our institution from08/2006to03/2012.Results:We presented here seven pediatric (adolescent) patients with botryoid rhabdomyosarcoma involving the uterine cervix. All these cases were offered fertility-sparing surgery. The first patient was offered cervical conization while other six patients underwent radical abdominal trachelectomy and pelvic lymph node biopsy. They all accepted multiagent chemotherapy and presented with favorable outcomes.Conclusion:In properly selected cases of cervical botryoid rhabdomyosarcoma, conservative surgeries should attempt to preserve reproductive function without compromising in survival. Radical abdominal trachelectomy and pelvic lymph node biopsy have appeared to secure local disease control. Radical abdominal trachelectomy with skills preserving uterine arteries may allow sufficient blood supply to maintain uterine viability and achieve future fertility, and thus benefit the adolescent patients. Part2. Exploratory Research on Lymph Node metastasis-related microRNA in Patients with Cervical CancerObjective:To screen microRNAs associated likely with lymph node metastasis in cervical cancer, and verify the relationship between microRNAs’regulation and tumor metastasis in cervical cancer cell lines. This study was aimed at finding certain microRNA to regulate lymph node metastasis, showing regulatory network, offering experimental evidence for further investigation and finally utilizing microRNAs as markers for predicting lymph nodes metastasis in cervical cancerMethods and Materials:We hypothesize that miRNAs interconnect with mRNA involved in lymph node metastasis, which influence intrinsic metastasis ability of tumor. We obtain the miRNAs associated likely with lymph node metastasis through screening miRNAs expression profiling in primary cervical cancers with and without positive lymph node using microarray. Furthermore, we try to obtain lymph node metastasis-related miRNAs by screening miRNAs expression profiling in the same patient’s ’primary lesion’ and ’metastatic lymph node’. Those differentially expressed miRNAs come from the same ecological background and may have direct relationship with lymph node metastasis. In order to test the result of microarray, Real-time Polymerase Chain Reaction is performed. Transwell experiment in cell strains would be employed to verify the relationship between miRNAs expression and lymph node metastasis. Furthermore, prediction algorithms TargetScan will be used to analyze the possible trget gene.Results:MiRNA microarray showed that four miRNAs (has-miR-142-3p, has-miR-550a, has-miR-652and has-miR-H18) were overexpressed in cervical cancer samples with positive lymph nodes, when compared to the cervical cancer samples without positive lymph nodes, while three miRNAs (has-miR-320b, has-miR-196b and has-miR-424) were underexpressed. Three miRNAs’expression (has-miR-630, has-miR-223and has-miR-451) were found statistically different by screening miRNAs expression profiling in seven patients’’primary lesion’ and ’metastatic lymph node’. Squamous cancer cell line Caski was transfected by has-miR-652-mimic. Transwell experiment in Caski cell strain revealed the metastatic ability of tumor cell was significantly improved after miR-652-mimic’s transfection. Furthermore, prediction algorithm TargetScan was used to analyze the possible target gene. Eight genes, ISL1included, became the candidates.Conclusions:The preliminary results of our exploratory research showed that differently expressed microRNAs detected from cervical cancer samples with and without lymph node metastasis had functional meaning. Further study, either in vitro or in vivo, is needed to to figure out the mechanism of microRNA-regulated lymph node metastasis, and establish an microRNA model to predict lymph node metastasis in cervical cancer, thus offer evidence for personalized treatment and possible gene therapy. |
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