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To evaluate the impact on urodynamic results between the laparoscopic nerve-sparing radical hysterectomy (LRH) following a step-by-step procedure and abdominal nerve-sparing radical hysterectomy (ARH) for patients with uterine cervical cancer.This retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S-100 antibody staining.Estimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p = 0.044). There was no difference in perioperative complications between the two groups in this study. The 5-year disease-free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1 month, and the LRH group had a smaller number of s-100 antibody stained nerves contained the parametrial sections.We demonstrated that LRH following a step-by-step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.

Background: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. Methods: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. Results: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. Conclusion: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.

OBJECTIVE: Our purposes of this study were to characterize a group of bulky cervical cancer patients who underwent a nerve sparing radical hysterectomy (NSRH) with or without neoadjuvant chemotherapy (NAC), to compare surgical outcomes and the preservation of bladder function, and to compare prognoses. RESULTS: Fifty-three patients had NSRH without NAC (Group A), and 33 patients had NSRH after NAC (Group B). With regard to prognostic factors, there was only a significant difference between both groups with regard to lymph node metastasis (15% vs 42%, P = 0.01). Moreover, bladder function in Group B patients improved to the same extent as the preoperative rate three months postoperatively. These data were similar to the results in Group A. With regard to overall survival, the 5-year survival rate was 98.1% (95% confidence interval (CI) 87.8-99.7) in Group A and 86.7% (95% CI 71.7-96.7) in Group B (P > 0.1). METHODS: We retrospectively identified 86 patients with cervical cancer who underwent NSRH at Osaka Medical College from May 2009 to November 2016. NAC was performed via balloon occluded arterial infusion. We extracted data on the patient's stage of progress, tumor volume, histological subtype, bleeding volume, urodynamic study results, and postoperative complications. The data were divided into two groups - those patients who received NAC and those who did not - and then compared. CONCLUSIONS: According to our analysis, NSRH surgery after NAC via balloon occluded arterial infusion brings beneficial results to patients with bulky IB2 to IIB cervical cancers.

Tomohito Tanaka,1 Shunsuke Miyamoto,1 Shinichi Terada,1 Yuhei Kogata,1 Hiroshi Sasaki,1 Satoshi Tsunetoh,1 Takashi Yamada,2 Masahide Ohmichi11Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Japan; 2Department of Pathology, Osaka Medical College, Takatsuki, JapanPurpose: Although laparoscopic radical hysterectomy (LRH) has been performed for patients with cervical cancer because of its minimal invasiveness, a recent large prospective study showed that LRH was associated with a lower rate of disease-free survival and overall survival. However, the reason for these results is not apparent. The aim of this study was to evaluate the tumor spillage during LRH with vaginal closure without the use of a manipulator.Patients and methods: Twenty-four patients with cervical cancer underwent total LRH with vaginal closure. To evaluate the leakage of cancer cells during surgery, peritoneal cytology was performed before and after hysterectomy.Results: Among 24 patients with cervical cancer, 2 had stage IA2 disease, 19 had stage IB1 disease and 3 had stage IIA1 disease. Two patients had lymph node metastasis. The median tumor size on final pathology was 9 mm. No cancer cells were identified before or after hysterectomy in any patients.Conclusion: Total LRH with vaginal closure did not increase the propensity for tumor spillage in the peritoneal cavity.Keywords: cervical cancer, laparoscopy, radical hysterectomy, vaginal closure

Background: Because patient-derived xenograft (PDX) models resemble the original tumors, they can be used as platforms to find target agents for precision medicine and to study characteristics of tumor biology such as clonal evolution and microenvironment interactions. The aim of this review was to identify articles on endometrial cancer PDXs (EC-PDXs) and verify the methodology and outcomes. Methods: We used PubMed to research and identify articles on EC-PDX. The data were analyzed descriptively. Results: Post literature review, eight studies were selected for the systematic review. Eighty-five EC-PDXs were established from 173 patients with EC, with a total success rate of 49.1%. A 1–10 mm3 fragment was usually implanted. Fresh-fragment implantation had higher success rates than using overnight-stored or frozen fragments. Primary tumors were successfully established with subcutaneous implantation, but metastasis rarely occurred; orthotopic implantation via minced tumor cell injection was better for metastatic models. The success rate did not correspond to immunodeficiency grades, and PDXs using nude mice reduced costs. The tumor growth period ranged from 2 weeks to 13 months. Similar characteristics were observed between primary tumors and PDXs, including pathological findings, gene mutations, and gene expression. Conclusion: EC-PDXs are promising tools for translational research because they closely resemble the features of tumors in patients and retain molecular and histological features of the disease.

// Tomohito Tanaka 1 , Yoshito Terai 1 , Satoe Fujiwara 1 , Yoshimichi Tanaka 1 , Hiroshi Sasaki 1 , Satoshi Tsunetoh 1 , Kazuhiro Yamamoto 2 , Takashi Yamada 3 and Masahide Ohmichi 1 1 Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Japan 2 Department of Radiology, Osaka Medical College, Takatsuki, Japan 3 Department of Pathology, Osaka Medical College, Takatsuki, Japan Correspondence to: Yoshito Terai, email: y-terai@osaka-med.ac.jp Keywords: uterine cervical cancer; locally advanced uterine cervical cancer; neoadjuvant chemotherapy; radical hysterectomy Received: June 05, 2018 Accepted: December 13, 2018 Published: December 28, 2018 ABSTRACT OBJECTIVE: We report a balloon-occluded arterial infusion therapy with an original four-lumen double-balloon catheter (4L-DB) which allows for the efficient injection of an anticancer agent at a high concentration to the target spot for patients with locally advanced uterine cervical cancer. METHODS: One hundred and forty-three patients with locally advanced cervical cancer treated with neoadjuvant intra-arterial chemotherapy (NAIAC) or a primary radical hysterectomy (PRH) were retrospectively assessed. The patients in the NAIAC group received irinotecan 70 mg/m2 intravenously on day 1 and 8 and cisplatin 70 mg/m2 intra-arterially using the 4L-DB on day 2 of a 21-day course, and two courses were performed in principle. The radical hysterectomy was performed within 6 weeks after NAIAC. RESULTS: Ninety-four patients were treated with NAIAC, and 49 patients undertook a PRH. The response rate of NAIAC on MRI was 92.6%. Fourteen patients (14.6%) had no evidence of cancer cells on pathologic diagnoses. The NAIAC group had a longer disease-free survival than the PRH group (p=0.02); however, the overall survival was not significantly different. The relative risk (RR) for recurrence was higher in patients with lymph node metastasis (RR, 4.31; 95% CI, 2.23-8.43) and lower in those who underwent NAIAC (RR, 0.30; 95% CI, 0.14-0.68). CONCLUSION: Our results with NAIAC using the 4L-DB catheter in locally advanced cervical cancer indicates beneficial effects on primary lesions and improves disease-free survival.

Objective The histological tumor grade is a strong predictor of nodal metastasis in endometrial cancer; as such, an accurate pre- or intraoperative diagnosis is important for performing lymphadenectomy. Methods Ninety-one patients with endometrioid endometrial cancer were imaged on DW-MRI with the apparent diffusion coefficient (ADC) calculated and a frozen section (FS) diagnosis made before and at hysterectomy. The diagnostic accuracy for predicting the tumor grade for diffusion weighted magnetic resonance inaging (DW-MRI) and the FS diagnosis compared to the ultimate histologic status was analyzed. Results Among 91 patients with endometrioid endometrial cancer, high-grade (endometrioid G3) tumors had lower ADC values than low-grade (endometrioid G1/2) tumors. The cut-off of the mean ADCmean values for predicting high-grade tumors resulted in 743×10-6 mm2/sec according to the receiver operating characteristic curve. The true positive rates of ADC values and FSs for the prediction of high-grade tumors did not differ to a statistically significant extent (73.3% vs. 66.7%, p=0.7), however, the true negative rate of ADC values for the prediction of low-grade tumors was significantly lower than that of the FSs (64.5% vs. 98.7%, p=0.01). The kappa statistics of ADC values and FSs were 0.23 and 0.73, respectively. Of note, all five patients with high-grade tumors for whom intraoperative FSs indicated low-grade tumors were predicted to have high-grade tumors on preoperative DW-MRI. Conclusion A FS diagnosis is more suitable for predicting high-grade tumors than DW-MRI; however, physicians should pay close attention to tumors with low ADC values on preoperative DW-MRI.

Background It is well known that ovarian mature cystic teratomas (MCTs) occasionally go through malignant transformations. Among these, approximately 75% of histological types are squamous cell carcinoma, with the other types being exceptionally rare. We report an extremely rare case of ovarian clear cell carcinoma arising from ovarian mature cystic teratoma. Case presentation The case was a 71-year-old woman with abdominal distention. Ultrasonography and magnetic resonance imaging showed a huge mass in her abdominal cavity. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed FDG uptake not only in the pelvic tumor but also in the hepatic nodule, thus suggesting metastases. We performed a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and an omentectomy. The pathological diagnosis showed clear cell carcinoma of the right ovary which arose from the MCT with malignant transformation pT2aNXM1. Although the patient underwent chemotherapy, she died after 17 months. Conclusion This case is histologically characteristic of the proof of transition from simple squamous epithelium via simple glandular epithelium to papillary change with atypia. This is the first case report of unaccompanied clear cell carcinoma arising from MCT reported in English literatures.

Background: The examination of a sentinel lymph node (SLN), where lymph node metastasis first occurs, may be advocated as an alternative staging technique. The aim of this study was to evaluate the feasibility and detection rates of an SLN biopsy in patients with endometrial cancer. Study design: Two hundred and eleven patients with endometrial cancer underwent an SLN biopsy at hysterectomy using three kinds of tracers including 99m-technetium-labeled tin colloid (99mTc), indigo carmine and indocyanine green. Factors related to the side-specific detection rate, sensitivity and false negative rate were analyzed. Results: The detection rates of the SLN biopsy using 99mTc, indigo carmine and indocyanine green were 77.9, 17.0 and 73.4%, respectively. The detection rate was lower in elderly patients (≥60 years) (67.9 vs 89.2%, p < 0.01), patients with >50% myometrial invasion (68.3 vs 85.2%, p < 0.01), patients with high-grade tumors (69.5 vs 84.9%, p < 0.01) and patients who underwent laparotomy (71.2 vs 84.9%, p < 0.01). There were no significant differences in body mass index. The sensitivity was not significantly different in any factor. However, the false negative rate was higher in patients with > 50% myometrial invasion (11.5 vs 1.2%, p < 0.01), high-grade tumors (13.3 vs 0.8%, p < 0.01) and who underwent laparotomy (12.2 vs 0.4%, p < 0.01). Conclusion: Patients who underwent laparoscopy with < 50% myometrial invasion and low-grade tumors not only have higher detection rates, but also have lower false negative rates. These patients may avoid systemic lymphadenectomy according to the status of the SLN biopsy.

The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma. We demonstrated that CD24 was expressed in 70.1% of primary ovarian carcinoma tissues, which were obtained from 174 patients, and that the expression of CD24 was an independent predictor of survival in patients with ovarian cancer. The expression of CD24 has been found to be correlated with the FIGO stage, presence of peritoneal and lymph node metastasis. CD24 induces the EMT phenomenon, which is involved in cell invasion, the highly proliferative phenotype, colony formation and which is associated with cisplatin resistance and the properties of CSCs, via the activation of PI3K/Akt, NF-κB and ERK in Caov-3 cisplatin-resistant cell lines. CD24-positive ovarian carcinomas have been shown to have a greater potential for intra-abdominal tumor cell dissemination in in vivo models. Our findings suggest that CD24 induced the EMT phenomenon in ovarian cancer, and that CD24 amplified cell growth-related intracellular signaling via the PI3K/Akt and MAPK pathways by affecting the EMT signal pathways. We believe that CD24 is a key molecule of metastatic progression in the EMT phenomenon and a promising therapeutic target for advanced ovarian cancer.

CD24, a small heavily glycosylated mucin-like glycosylphosphatidylinositol-anchored cell surface protein, plays an important role in the carcinogenesis of various human malignancies. However, its function in cervical cancer remains unclear. The aim of the present study was to evaluate the expression of CD24 clinicopathologically and to analyze its functional behavior biologically in cervical cancer. A total of 117 uterine cervical cancer tumors were immunohistochemically analyzed using a CD24 monoclonal antibody on paraffin blocks. We also examined whether CD24 enhanced the invasive activity or the Akt, ERK, NF-κB and MMP activity in a uterine cervical cancer cell line (CaSki) by a western blot analysis. The patients with enhanced CD24 expression had a higher rate of advanced clinical stage (50 vs. 16.5%, p

Background PD-0332991, the selective cyclin-dependent kinase 4/6 inhibitor palbociclib, causes cell cycle arrest by inhibiting phosphorylation of retinoblastoma (Rb) protein. The aim of this study was to evaluate the therapeutic potential of PD-0332991 in endometrial cancer. Methods and findings Four human endometrial cancer cell lines, ECC, HEC1A, HEC108 and TEN, were treated with PD-0332991 and their function was evaluated. In vivo, the therapeutic efficacy was evaluated in a model of subcutaneous endometrial cancer. An immunohistochemical analysis was performed in 337 endometrial cancer specimens. A proliferation assay revealed that 2 of the 4 cell lines that expressed Rb were sensitive to PD-0332991 with an IC50 of 0.65 μM (HEC1A) and 0.58 μM (HEC108), respectively. Both cell lines had G0/G1 cell cycle arrest after treatment with PD-0332991 according to flow cytometry. In vivo, PD-0332991 had antitumoral efficacy with a reduction in the activity of Ki67 and phosphorylation of Rb. Immunohistochemical analyses revealed that the positive rate of Rb was 67.7%, however, there was no significant relationship between the expression levels of Rb and the tumor grade. Conclusions PD-0332991 had therapeutic potential against endometrial cancer cell lines expressing Rb protein. Our immunohistochemical analysis revealed that approximately 70% of patients with endometrial cancer might have therapeutic indications for PD-0332991. Of note, the tumor grade had no impact on the indications for treatment.

Rationale: Uterine leiomyoma, which is very common gynecological tumor in the reproductive years, is extremely rare in adolescence. We herein report a case of a uterine leiomyoma treated with laparoscopic surgery in an adolescent. Patient concerns: A 13-year-old girl with no gravida and her first menses at 11 years of age reported feeling bloated. She had a regular menstrual cycle but felt increased abdominal distension. Diagnosis: Transabdominal ultrasound and magnetic resonance imaging revealed uterine leiomyoma with a diameter of 10 cm. Intervention: Laparoscopic myomectomy was performed. Outcomes: The total weight of the leiomyoma removed was 660 g with pathological diagnosis of uterine leiomyoma. The postoperative course was uneventful. The patient was free of disease at the follow-up consultation 18 months after the treatment. Lessons: Laparoscopic approach is a very useful and minimally invasive surgery for symptomatic leiomyoma in adolescents.

e17041 Background: G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that the high expression of GPR30 is associated with a poor prognosis in breast cancer or endometrial cancer. Although the role of GPR30 in ovarian cancer was unclear, we revealed that GPR30 is associated with poor prognosis in ovarian cancer. On the other hand, Epithelial-to-Mesenchymal Transition (EMT) is involved in cancer metastasis. The purpose of this study is to reveal how GPR30 was associated with poor prognosis and whether associated with EMT in ovarian cancer. Methods: We examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis. We also examined the effect of GPR30 on EMT were evaluated in Caov-3, which were cultured both in two-dimensional (2D) culture and three-dimensional (3D) culture model. GPR30 agonist, G1, was used to confirm the regulatory effects of GPR30 on the change of phenotypic modulation and EMT markers expression. Results: The phosphorylation of the EGFR and Akt could be significantly enhanced by G1 (p < 0.05) and inhibited by a Src family kinase inhibitor. In 3D culture, the stimulation of GPR30 leads the floating and sphere formation in Caov-3. G1-induced EMT was observed with related regulation of EMT markers expression at both mRNA and protein level. G1 induced the decrease of E-cadherin level and the increase of Snail and Vimentin in RT-PCR and Western blotting. Knockdown of GPR30, using siRNA, blocked G1-induced EMT. Conclusions: GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells and changes ovarian cancer cells to the EMT state.GPR30 might be an important molecule related to metastasis process in ovarian cancer.

Aim This is the first report to determine the feasibility and safety of total laparoscopic modified radical hysterectomy (TLMRH) in the treatment of presumed stage I endometrial cancer. Methods This was a retrospective study of 132 consecutive patients who underwent surgery for early endometrial cancer. Thirty-nine patients underwent TLMRH and bilateral salpingo-oophorectomy (BSO), and 93 had a total abdominal extrafascial hysterectomy and BSO. Lymphadenectomy was performed in 87 patients. The groups were compared for epidemiological and clinical characteristics, surgical outcomes, hospital stay, lymph nodes harvested, and intraoperative and postoperative complications. Results The patients in the TLMRH group had less blood loss (42.9 ± 76.3 vs 236.8 ± 186.6 mL, P

Aim The purpose of this study was to compare the intraoperative and postoperative parameters among the three approaches used to treat large uterine myomas: laparoscopic assisted vaginal hysterectomy (LAVH), total laparoscopic hysterectomy (TLH) and abdominal hysterectomy, and to evaluate the selection criteria for laparoscopic hysterectomy as determined by magnetic resonance imaging. Material and Methods The medical records of 155 patients who underwent a hysterectomy between January 2007 and April 2010 were examined. We also compared the indications and outcomes of LAVH and TLH for myomas larger than 7 cm. Results Patients who underwent LAVH or TLH had a lower average intraoperative blood loss, less intense postoperative pain, and shorter hospital stays than patients in the TAH group, although the length of the operations in the laparoscopic groups were significantly longer. To evaluate the selection criteria for the large sized myomas, we compared the LAVH and TLH groups for the myomas larger than 7 cm. The greatest uterine transverse diameters and the weight of the uteri were not significantly different between the LAVH and TLH groups (94.7 ± 20.8 and 83.1 ± 17.6 mm, 371.6 ± 160.3 and 286.7 ± 158.0 g, respectively). The average intraoperative blood loss in the TLH group was significantly lower than that in the LAVH (121.3 ± 111.2 vs 379.3 ± 222.4 g, P

Objectives: The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of E-cadherin expression, which is mainly controlled by Snail-related zinc-finger transcription factors (Snail and Slug). The aim of this study was to evaluate the prognostic impact of EMT-related protein (E-cadherin, Snail and Slug) expression in endometrial cancer. Methods: An immunohistochemical analysis was conducted using tissue microarray samples of 354 primary tumors and 30 metastases of endometrial carcinomas, and the relationship between protein expression, clinicopathological features and outcomes were investigated. Results: Reduced E-cadherin was seen in 39.8% of primary tumors. Reduced E-cadherin was seen in 19.5%, 40.8% and 72.7% of G1, G2 and G3 endometrioid adenocarcinomas, respectively. The nuclear expression of Snail and Slug were positive in 16.9% and 3.7% of primary tumors, respectively. EMT status, which was represented by both reduced E-cadherin and nuclear expression of Snail, was significantly associated with histological type, FIGO stage, myometrial invasion, positive peritoneal cytology and patient survival (p < 0.01). There was no difference in the rates of EMT status between the primary tumors and metastases. A multivariate analysis showed that EMT-positive status was a significant predictor for both the progression-free survival and overall survival (p < 0.01). Conclusions: These data indicate that EMT status has a prognostic impact in endometrial cancer. Therefore, the clarification and control of EMT signaling is a promising molecular targeting therapy in endometrial cancer.

OBJECTIVE Our objective was to determine the feasibility and detection rates and clarify the most effective combination of injected tracer types for sentinel lymph node (SLN) mapping in uterine cervical cancer in patients who have undergone laparoscopic surgery or neoadjuvant chemotherapy (NAC). METHODS A total of 119 patients with cervical cancer underwent SLN biopsy at radical hysterectomy using three types of tracers. The various factors related to side-specific detection rate, sensitivity, and false negative (FN) rate were analyzed. RESULTS The SLN detection rates using 99m-technetium ((99m)Tc)-tin colloid, indigo carmine, and indocyanine green (ICG) were 85.8%, 20.2%, and 61.6%, respectively. The patients with ≥2-cm-diameter tumors and those who received NAC had lower detection rates than those with

Purpose: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded as a promising therapeutic target. We hypothesized that treatment with bevacizumab, a humanized recombinant anti-VEGF monoclonal antibody, could enhance antitumor response to cisplatin and prolong survival in a murine ovarian cancer model.Experimental Design: We conducted an MTS assay to examine the effect of bevacizumab on proliferation of the VEGF producing human ovarian cancer cell lines in vitro. Next, the antiangiogenic activity of bevacizumab was investigated by in vivo angiogenesis and wound healing assays. We then determined the toxicity and antitumor response of bevacizumab and cisplatin as single agents or in combination in xenograft models of ovarian cancer. Finally, using the same xenograft model, we examined the effect of these regimens, as well as bevacizumab maintenance therapy, on survival.Results: Bevacizumab had no effect on the proliferation of ovarian cancer cells in vitro but significantly inhibited angiogenesis and delayed wound healing in vivo. Bevacizumab inhibited i.p. tumor growth and ascites production in the nu/nu mouse xenograft model and enhanced the therapeutic efficacy of cisplatin. Combination therapy with bevacizumab and cisplatin for 3 weeks was associated with complete disappearance of all macroscopic evidence of disease. Moreover, maintenance treatment with bevacizumab after 3 weeks of induction combination therapy inhibited recurrence and significantly prolonged survival.Conclusions: Bevacizumab has significant antitumor activity not only as a single agent or in combination with cisplatin but may also prolong survival when used as maintenance therapy after a complete response to cisplatin-based chemotherapy.

Objective The rate of lymph node metastasis is extremely low in patients with low-risk endometrial cancer; lymphadenectomy may be unnecessary for these patients under an accurate preoperative diagnosis. The aim of this study was to evaluate the diagnostic accuracy of myometrial invasion (MI) on preoperative magnetic resonance imaging (MRI) and intraoperative frozen sections (FSs). Materials and Methods Endometrial cancer was diagnosed in a total of 378 patients by preoperative endometrial curettage, preoperative magnetic resonance imaging MRI, and intraoperative FSs; the 378 patients underwent hysterectomy. The depth of MI was evaluated between the preoperative MRI, intraoperative FSs, and final paraffin sections (PSs). The histologic grade was also evaluated between preoperative endometrial curettage, intraoperative FSs, and final PSs. Results The sensitivity, specificity, positive predictive value, and negative predictive value for deep MI (≥50%) on MRI were 57.8%, 92.0%, 69.3%, and 87.5%, respectively, with a kappa value of 0.53. These figures on FSs were 66.7%, 97.9%, 90.9%, and 90.4%, with a kappa value of 0.71. When grade 3 endometrioid adenocarcinoma, serous carcinoma, clear cell carcinoma, and carcinosarcoma were considered high-grade tumors, the grade evaluation at the time of FSs was 70.2%, 99.0%, 96.1%, and 89.7%, with a kappa value of 0.75. In the patients with low-grade tumors, including grade 1 or 2 endometrioid adenocarcinoma on preoperative endometrial curettage, the rate of unexpected lymph node metastasis did not differ significantly between the patients who had a diagnosis of MI and lymph node metastasis by MRI and those with diagnosis of MI and histological grade by FSs (4.0% vs 2.6%; P > 0.05). Conclusions Frozen sections had a higher agreement rate for MI than MRI; however, MRI is still considered an acceptable modality to guide preoperative decisions regarding lymphadenectomy especially in grade 1 or 2 endometrioid adenocarcinoma.

Objective The aim of this study was to estimate the incidence, etiology, and outcomes of genitofemoral neuropathy after pelvic lymphadenectomy (PLD) for uterine corpus cancer. Materials and Methods The medical records of women who underwent PLD for uterine corpus cancer between June 2001 and June 2013 were reviewed. Information regarding neuropathy was directly reported by each subject. Results Thirty-two of 300 patients undergoing PLD during the defined period experienced postoperative neuropathy due to genitofemoral nerve injury, for an incidence of 10.7%. The patients treated with PLD with para-aortic lymphadenectomy (PALD) exhibited a lower rate of genitofemoral neuropathy than those treated without PALD (4.3% vs 13.5%, P = 0.01). The laparoscopy group displayed a higher rate of genitofemoral neuropathy than the laparotomy group (19.1% vs 9.1%, P = 0.04). A total of 81.3% of the patients experienced a full recovery, with a medium time to resolution of 6 months (3–12 months). The administration of adjuvant chemotherapy, including paclitaxel, did not extend the time to recovery. Conclusions Neuropathy resulting from genitofemoral nerve injury is not infrequent; however, most of the patients recover completely. In this study, the use of laparoscopic procedures increased the incidence of genitofemoral neuropathy, whereas that of PALD did not.

Objectives The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of the E-cadherin expression, which is primarily controlled by Snail-related zinc-finger transcription factors. The aim of this study was to evaluate the prognostic impact of the expression of EMT-related proteins (E-cadherin and Snail) in patients with ovarian cancer. Methods An immunohistochemical analysis was conducted using tissue microarray samples of 174 primary tumors and 34 metastases of ovarian carcinoma, and the relationships between the protein expression, clinicopathological features and outcomes were investigated. Results A reduced E-cadherin expression was observed in 36.8% of the primary tumors and 30.4%, 35.7%, 37.7% and 52.7% of the stage I, II, III and IV tumors, respectively. The nuclear expression of Snail was positive in 33.9% of the primary tumors. The rate of an EMT-positive status, as represented by both a reduced E-cadherin expression and a nuclear expression of Snail, was significantly higher in the patients with peritoneal dissemination than in those without (p

Objectives To introduce a safe and reliable method for the management of peripheral vessels around the uterine artery during abdominal radical hysterectomy or abdominal radical trachelectomy. Study design From 2007 to 2011, 102 patients with invasive cervical cancer underwent an abdominal radical hysterectomy. In 48 operations in 2007–2009, we performed the conventional radical hysterectomy, in which we ligated and cut the uterine arteries at their origin, and we divided the anterior leaf of the vesico-uterine ligament by blindly inserting scissors into the ureteral tunnel, pushing the ureter laterally from the cervix. In 54 operations in 2009–2011, we pulled up the origin and the bifurcation of the uterine artery using vessel tape, skeletonized the uterine artery and directly divided the superficial uterine vein, superior vesical vein and ureteric branch of the uterine artery. We also performed four radical trachelectomies using the two point pull-up method. We investigated whether this method was useful for the management of peripheral vessels around the uterine artery. Results The mean total blood loss in the two point pull-up method group (485 ± 270 ml) was significantly lower than that in the conventional surgery group (686 ± 554 ml) (p

Background Mature cystic teratomas (MCTs) are the most common germ cell tumors of the ovary. Malignant tranformation occurs in 1-2% of these neoplasms. Although most of the malignancies arising from MCTs are squamous cell carcinomas, adenocarcinoma of the gastrointestinal type is extremery rare. We herein present a case of adenocarcinoma of the intestinal type arising from a MCT. Case A 49-year-old female underwent surgery for a left ovarian tumor. The histology of the cyst walls revealed a MCT with a few hair shafts and a squamous layer, while another part of the tumor showed adenocarcinoma of the intestinal type. Five years after surgery, she is alive without disease.

Objectives G protein-coupled receptor 30 (GPR30) is a 7-transmembrane estrogen receptor that functions alongside traditional estrogen receptors to regulate the cellular responses to estrogen. Recent studies suggest that GPR30 expression is associated with a poor prognosis, and that this is due to the GPR30-mediated transactivation of the EGFR in breast cancer. However, the biological contribution of GPR30 in ovarian cancer remains unclear. The purpose of this study was to elucidate the relationships between GPR30 expression and the clinicopathological findings, and to determine how the signaling cascade influences the prognosis of ovarian cancer. Methods The expression levels of GPR30, EGFR, ERα, and ERβ were analyzed using an immunohistochemical analysis, and their correlations with the clinicopathological features were examined in 10 patients with borderline malignant tumors and 152 patients with epithelial ovarian cancer. We also examined whether GPR30 signaling activates the EGFR-Akt pathway in an ovarian cancer cell line (Caov-3) by a Western blotting analysis. Results The GPR30 expression in ovarian carcinomas was significantly higher than that in borderline malignancies (p=0.0016), and was not associated with the expression of the EGFR, ERα, or ERβ. The expression of GPR30 in clear cell carcinomas was significantly lower than that in other subtypes of cancer (P Conclusion The expression of both GPR30 and EGFR is associated with a poor outcome in ovarian cancer, and GPR30 increases the phosphorylation of Akt via the EGFR in ovarian cancer cells. The regulation of GPR30 might be a potentially useful new therapeutic target in ovarian cancer.

The aim of this study was to evaluate the effect of our novel technique on the prevention of postoperative ileus in patients undergoing systematic para-aortic lymphadenectomy (PALN).PALN was performed in 135 gynecological cancer patients (67 with ovarian cancer, 58 with endometrial cancer, 8 with serous surface papillary adenocarcinoma (SSPC) and 2 with fallopian tube cancer) between 2006 and 2011. To prevent postoperative ileus, we performed our novel technique wherein the small bowel and colon are released from pressure and soaked in 2 L of physiological saline for 1 min every 20 min during the lymphadenectomy. We indicated our novel PALN technique and retrospectively analyzed the outcomes of the surgical procedure in terms of the surgical data, and postoperative incidence of gastrointestinal dysfunction in patients with gynecological malignancies.The mean blood loss was 641.2 ± 800.3 mL in the PALN group and 313.9 ± 278.9 mL in the pelvic lymphadenectomy (PLN) without PALN group (P0.0001). There was no difference in the first passage of flatus between the PALN group and the PLN group (1.8 ± 0.7 days vs 1.6 ± 0.7 days). The mean time to tolerance of a regular diet was significantly longer in the PALN group than in the PLN group (P0.0001), whereas the incidence of vomiting was similar in both groups. Surprisingly, there were no cases of postoperative ileus in either group.Our novel technique is a safe and effective way to prevent the incidence and decrease the severity of postoperative ileus after PALN for gynecological malignancies.

The purpose of this study was to compare the intraoperative and postoperative parameters among the three approaches used to treat large uterine myomas: laparoscopic assisted vaginal hysterectomy (LAVH), total laparoscopic hysterectomy (TLH) and abdominal hysterectomy, and to evaluate the selection criteria for laparoscopic hysterectomy as determined by magnetic resonance imaging.The medical records of 155 patients who underwent a hysterectomy between January 2007 and April 2010 were examined. We also compared the indications and outcomes of LAVH and TLH for myomas larger than 7 cm.Patients who underwent LAVH or TLH had a lower average intraoperative blood loss, less intense postoperative pain, and shorter hospital stays than patients in the TAH group, although the length of the operations in the laparoscopic groups were significantly longer. To evaluate the selection criteria for the large sized myomas, we compared the LAVH and TLH groups for the myomas larger than 7 cm. The greatest uterine transverse diameters and the weight of the uteri were not significantly different between the LAVH and TLH groups (94.7 ± 20.8 and 83.1 ± 17.6 mm, 371.6 ± 160.3 and 286.7 ± 158.0 g, respectively). The average intraoperative blood loss in the TLH group was significantly lower than that in the LAVH (121.3 ± 111.2 vs 379.3 ± 222.4 g, P0.001).Our data suggest that TLH is a better procedure for treating a large uterus no larger than 10 cm in its greatest transverse diameter. The preoperative total length of myoma nodules determined by MRI is a useful preoperative indicator of the uterine weight.

Topotecan, a novel topoisomerase-1 inhibitor, is a drug that appears to be effective against platinum-resistant ovarian cancers. However, the molecular mechanisms by which Topotecan treatment inhibits cancer cell proliferation are unclear. We investigated whether Topotecan increases the efficacy of Cisplatin in platinum-resistant ovarian cancer models in vitro and in vivo.We used Cisplatin-resistant Caov-3 cells and Cisplatin-sensitive A2780 cells. We examined the effect of Cisplatin and Topotecan on the cell viability of Caov-3 and A2780 cells by MTS assay. We examined the Akt kinase activity, VEGF and HIF-1α expression after Cisplatin and Topotecan by a Western blot analysis. Moreover, we also evaluated the effects of Cisplatin and Topotecan on the intraabdominal dissemination of ovarian cancer in vivo.Topotecan significantly inhibited Cisplatin-induced Akt activation in Caov-3 cells, but not in A2780 cells. In the presence of Topotecan, Cisplatin-induced growth inhibition and apoptosis were significantly enhanced in Caov-3 cells. Topotecan inhibited not only Cisplatin-induced Akt activation but also VEGF and HIF-1α expression. Moreover, treatment with Topotecan increased the efficacy of Cisplatin-induced growth inhibition in the intraabdominal dissemination and production of ascites in athymic nude mice inoculated with Caov-3 cells.We herein demonstrated that Topotecan inhibits Akt kinase activity and VEGF transcriptional activation after Cisplatin treatment in platinum-resistant ovarian cancers. We clarified how Topotecan enhanced the clinical activity in the platinum-resistant ovarian cancer. These results provide a rationale for using Topotecan in clinical regimens aimed at molecular targeting agents in platinum-resistant ovarian cancers.

We report the therapeutic potential, longterm survival, and toxicity of neoadjuvant intraarterial chemotherapy (NAIC) using an original four-lumen double-balloon (4L-DB) catheter followed by radical hysterectomy and/or radiotherapy in patients with locally advanced cervical cancer. Sixty patients with stage IIB-IVA cervical squamous cell cancer were treated with NAIC which included cisplatin (60–70 mg/m2, day 1), mitomycin-C (10–20 mg/m2, day 1), and pirarubicin hydrochloride (THP; 10–20 mg/m2, day 1) for two courses every 21 days. The median follow up among surviving patients was 93.7 months. Among 60 eligible patients, 22 had a complete response (CR; 36.7%) including 12 with a pathologic CR (20.0%). Thirty-six patients had a partial response (60.0%), and stable disease was observed in only 2 patients (3.3%). Moreover, we found that the platinum concentration in the cervix was correlated with the clinical response (P < 0.001). The 10-year progression-free survival (PFS) and 10-year survival were 90.9% and 90.9%, respectively, in patients with stage IIB disease and 66.0% and 70.7%, respectively, in patients with stage III disease. Leukopenia occurred in 86.7% of patients, but it was not very severe (grade 3, 4 in 13.3% of patients). Our results with NAIC using the 4L-DB catheter in locally advanced cervical cancer demonstrate that a high platinum concentration has beneficial effects on primary lesions and improves long-term progression-free and overall survival.

Objective: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT 3 receptor with/ without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. Methods: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. Results: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p

A 48-year-old woman was referred to the cardiology department due to a large mobile mass in the right ventricle. The patient had undergone radical hysterectomy and bilateral salpingo-oophorectomy for a uterine squamous cell carcinoma approximately 3.5 years before. In order to protect the patient from circulatory collapse, the intracardiac mass was resected surgically. A diagnosis of cardiac metastasis of the uterine cervical squamous cell carcinoma was confirmed histologically. Herein we discuss the possible therapeutic approach to and prognosis of this rare condition by reviewing 24 papers on intracardiac uterine cancer metastasis published in the past 10 years.

Background Gemcitabine (2′, 2′ –difluorodeoxycytidine) is one of many nonplatinum drugs that exhibit activity in recurrent, platinum-resistant ovarian cancer. However, the molecular mechanisms by which Gemcitabine treatment inhibits the proliferation of platinum-resistant ovarian cancer cells still remain unclear. We investigated whether Gemcitabine increases the efficacy of Cisplatin in platinum-resistant ovarian cancer models in vitro and in vivo. Methods We used Cisplatin-resistant Caov-3 cells, A2780CP cells and Cisplatin-sensitive A2780 cells to examine the sensitivity of the cell viability of Cisplatin and Gemcitabine using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and the sensitivity of the invasive activity of Cisplatin and Gemcitabine using an invasion assay with Matrigel. We examined the Akt kinase activity and matrix metalloproteinase 9 (MMP9) expression following Cisplatin and Gemcitabine treatment using a Western blot analysis and the mRNA expression of vascular endothelial growth factor (VEGF) using semi-quantitative RT-PCR. Moreover, we evaluated the effects of Cisplatin and Gemcitabine on the intra-abdominal dissemination of ovarian cancer in vivo. Results Gemcitabine significantly inhibited Cisplatin-induced Akt activation in the Caov-3 and A2780CP cells, but not in the A2780 cells. In the presence of Gemcitabine, Cisplatin-induced growth inhibition and apoptosis were significantly enhanced in the Caov-3 and A2780CP cells. Co-treatment with Cisplatin and Gemcitabine almost completely inhibited invasion of both types of cells through the Matrigel; however, neither Cisplatin nor Gemcitabine alone inhibited the invasion of both types of cells. Gemcitabine inhibited not only the Cisplatin-induced activation of Akt, but also the MMP9 and mRNA expression of VEGF. Moreover, treatment with Gemcitabine increased the efficacy of Cisplatin-induced growth inhibition of the intra-abdominal dissemination and production of ascites in the athymic nude mice inoculated with Caov-3 cells. Conclusions We herein demonstrated that Gemcitabine inhibits the Akt kinase activity and angiogenetic activity following treatment with Cisplatin in platinum-resistant ovarian cancer cells. These results provide a rationale for using Gemcitabine in clinical regimens containing molecular targeting agents against platinum-resistant ovarian cancers.