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With the development of machine learning and deep learning models, artificial intelligence is now being applied to the field of medicine. In oncology, the use of artificial intelligence for the diagnostic evaluation of medical images such as radiographic images, omics analysis using genome data, and clinical information has been increasing in recent years. There have been increasing numbers of reports on the use of artificial intelligence in the field of gynecologic malignancies, and we introduce and review these studies. For cervical and endometrial cancers, the evaluation of medical images, such as colposcopy, hysteroscopy, and magnetic resonance images, using artificial intelligence is frequently reported. In ovarian cancer, many reports combine the assessment of medical images with the multi-omics analysis of clinical and genomic data using artificial intelligence. However, few study results can be implemented in clinical practice, and further research is needed in the future.

A diagnostic biopsy for endometrial cancer is performed via dilation and curettage (D&C). However, D&C may miss endometrial cancer lesions due to of its ‘blind’ approach. Hysteroscopy is a useful method that can be used to detect endometrial cancer lesions. In addition, office hysteroscopy is easy to be scheduled and does not require anesthesia. The patient was a 40-year-old woman with suspected endometrial cancer; however, it could not be diagnosed by D&C and biopsy using hysteroscopy during hospitalization. Office hysteroscopy during the proliferative phase indicated that the suspicious endometrial cancerous lesion was minimal at the isthmus of the uterus with atypical vessels and a white spot, for which biopsy was performed. Pathological diagnosis was endometrioid carcinoma with squamous differentiation, G1. Therefore, total laparoscopic hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy were performed. In this case, it was difficult to detect minimal lesion in the secretory phase because the endometrial thickness hid the endometrial cancer. It is easy to perform office hysteroscopy in the proliferative phase. This case indicated that office hysteroscopy is a useful method to diagnose and perform biopsy for minimal lesions.

We encountered HPV6‐positive cervical papillary squamous cancer (PSCC) that was difficult to diagnose. The case was initially diagnosed and treated for condyloma. To the best of our knowledge, this is the first report of HPV6 infection in PSCC.

PI3K pathway signaling has received attention as a molecular target in clear cell ovarian carcinoma (CCOC). MDM2 is one of the AKT effectors in the PI3K pathway, which binds to and degrades p53. In this study, we aimed to clarify the prognostic significance of PIK3CA and MDM2 expression, and potential therapeutic effect of a dual inhibition of the PI3K pathway and MDM2.cDNA expression was evaluated by using microarray data using 75 samples of CCOC. DS-7423 (dual inhibitor of pan-PI3K and mTOR) and RG7112 (MDM2 inhibitor) were used on CCOC cell lines to evaluate cell proliferation, expression level of MDM2 related proteins, and apoptosis by MTT assay, western blotting, and flow cytometry. DS-7423 (3 mg/kg) and/or RG7112 (50 mg/kg) were orally administrated every day for three weeks, and the anti-tumor effect was evaluated using tumor xenografts, along with immunohistochemistry.Tumors with high expression of both PIK3CA and MDM2 showed significantly worse prognosis in expression array of 71 CCOCs (P = 0.013). Dual inhibition of the PI3K pathway by DS-7423 and MDM2 by RG7112 showed synergistic anti-proliferative effect in 4 CCOC cell lines without TP53 mutations. The combination therapy more robustly induced pro-apoptotic proteins (PUMA and cleaved PARP) with increase of sub G1 population and apoptotic cells, compared with either single agent alone. The combination therapy significantly reduced tumor volume in mice (P 0.001 in OVISE, and P = 0.038 in RMG-I) without severe body weight loss. Immunohistochemistry from the xenograft tumors showed that the combination treatment significantly reduced vascularity and cell proliferation, with an increase of apoptotic cell death.A combination therapy targeting the PI3K pathway and MDM2 might be a promising therapeutic strategy in CCOC.

The programmed cell death 1/programmed cell death 1 ligand 1 pathway was successfully targeted in cancer immunotherapy. Elevated interleukin‐17 (IL‐17), which is known in autoimmune diseases, has recently been recognized in cancer patients. We investigated the role of IL‐17 in the regulation of expression of programmed cell death 1 ligand 1 in ovarian cancer by evaluating changes in the number of IL‐17‐producing cluster of differentiation 4 helper T cells (Th17) and γδT cells (γδT17) in PBMC of 52 gynecological cancer patients (including 30 ovarian cancer patients) and 18 healthy controls. The occupancy ratio of Th17 and γδT17 was higher in ovarian cancer and endometrial cancer patients than in controls, determined by multi‐color flow cytometry (Th17: P

Laparoscopic port site endometriosis is less common in abdominal wall endometriosis, and malignant transformation of abdominal wall endometriosis is rare. We reported a case of mixed endometrioid and clear cell carcinoma arising from port site endometriosis. The patient was a 49-year-old woman with a history of laparoscopic excision of ovarian endometrioma. Physical examination revealed a subcutaneous solid tumor around the laparoscopic surgical scar. Imaging showed a suspicious malignancy. She underwent radical marginal resection of the abdominal wall tumor, flap reconstruction of the abdominal wall, hysterectomy, bilateral salpingo-oophorectomy and omental biopsy. Histological examination revealed mixed endometrioid and clear cell carcinoma. Computed tomography scan showed no evidence of recurrence after six cycles of chemotherapy. This is the first case of malignant transformation from laparoscopic trocar site endometriosis.

Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV), high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose, however, only in the GLBL101c group, two patients had complete regression (CR, regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed.

Radiation-based therapy is widely used for advanced cervical cancer. Prior radiation-based therapy is a potential risk factor for febrile neutropenia (FN). However, the effect of irradiation field size on the incidence of FN during recurrent cervical cancer treatment is unclear. This study aimed to investigate the relationship between prior irradiation field size and FN development during recurrent chemotherapy. This retrospective, observational study included cervical cancer patients who received recurrent chemotherapy between November 2006 and June 2020. The patients were classified into two groups based on the area of irradiation fields. The first group included patients with a history of whole pelvis (WP) irradiation (WP group). The second group had patients who underwent WP plus para-aortic lymph node (PAN) irradiation (WP + PAN group). The incidences of hematological toxicities and FN during the recurrent chemoradiotherapy were compared between the two groups. The FN incidence was significantly higher in the WP + PAN group than in the WP group (32.1% vs. 0%, P

Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.

Endometrial cancer is a ubiquitous gynecological disease with increasing global incidence. Therefore, despite the lack of an established screening technique to date, early diagnosis of endometrial cancer assumes critical importance. This paper presents an artificial-intelligence-based system to detect the regions affected by endometrial cancer automatically from hysteroscopic images. In this study, 177 patients (60 with normal endometrium, 21 with uterine myoma, 60 with endometrial polyp, 15 with atypical endometrial hyperplasia, and 21 with endometrial cancer) with a history of hysteroscopy were recruited. Machine-learning techniques based on three popular deep neural network models were employed, and a continuity-analysis method was developed to enhance the accuracy of cancer diagnosis. Finally, we investigated if the accuracy could be improved by combining all the trained models. The results reveal that the diagnosis accuracy was approximately 80% (78.91–80.93%) when using the standard method, and it increased to 89% (83.94–89.13%) and exceeded 90% (i.e., 90.29%) when employing the proposed continuity analysis and combining the three neural networks, respectively. The corresponding sensitivity and specificity equaled 91.66% and 89.36%, respectively. These findings demonstrate the proposed method to be sufficient to facilitate timely diagnosis of endometrial cancer in the near future.

The albumin-to-globulin ratio reflects both the nutrition and inflammation and predicts prognosis in patients with various malignancies. However, in cervical cancer patients who undergo surgery, its significance has yet to be established. A total of 247 cervical cancer patients who received surgical treatment at our institution between 2005 and 2017 were enrolled in this study. Preoperative data, such as the levels of serum albumin and serum globulin as well as the albumin-to-globulin ratio along with the other clinicopathological characteristics were retrospectively assessed, and their association with the overall survival was analyzed. Overall, 49 cases of recurrence and 26 deaths were observed during the median follow-up time of 58.6 months. A low albumin-to-globulin ratio (

Previous studies have suggested that histone methylation can modulate carcinogenesis and cancer progression. For instance, the histone methyltransferase SET and MYND domain containing 2 (SMYD2) is overexpressed in several types of cancer tissue. The aim of the present study was to determine whether SMYD2 could serve a therapeutic role in ovarian clear cell carcinoma (OCCC). Reverse transcription-quantitative PCR was used to examine SMYD2 expression in 23 clinical OCCC specimens. Moreover, OCCC cell proliferation and cell cycle progression were also examined following small interfering RNA-mediated SMYD2 silencing or treatment with a selective SMYD2 inhibitor. SMYD2 was significantly upregulated in clinical OCCC specimens, compared with normal ovarian tissue. In addition, SMYD2 knockdown decreased cell viability as determined via a Cell Counting Kit-8 assay. Moreover, the proportion of cells in the sub-G1 phase increased following SMYD2 knockdown, suggesting increased apoptosis. Treatment with the SMYD2 inhibitor LLY-507 suppressed OCCC cell viability. These results suggested that SMYD2 could promote OCCC viability, and that SMYD2 inhibition induced apoptosis in these cells. Thus, SMYD2 inhibitors may represent a promising molecular targeted approach for OCCC treatment.

Aim Carboplatin is a key drug for gynecologic cancers. However, hypersensitivity reactions (HSR) are major adverse effects that might necessitate carboplatin discontinuation. Desensitization is an effective method in patients who developed initial HSR and further required carboplatin treatment. Here, we aimed to evaluate our experience with the use of the carboplatin desensitization protocol in five patients at the University of Tokyo Hospital. Methods We established a four-step, 5-h desensitization protocol for our hospital. Observational and retrospective analyses were performed. Additionally, we have shared the patients' clinical information with the emergency department to ensure the safety of this protocol. Results Five patients with recurrent gynecological cancer were treated using this protocol. Four of the five patients were treated effectively and 28 of 29 desensitization protocols were completed successfully. In one patient, we switched to olaparib successfully after two courses of our protocol. One patient who developed grade 4 HSR during initial carboplatin administration developed grade 2 HSR and we discontinued the protocol. Conclusion The carboplatin desensitization protocol is very efficient. The outcome of our protocol was on a par with other protocols. To the best of our knowledge, this is the first study to indicate that switching to olaparib can be considered a suitable option in patients who develop HSR to carboplatin.

Background Soluble Fms-like tyrosine kinase-1 (sFLT1) as an anti-angiogenic factor is abundantly expressed in placental trophoblasts. Choriocarcinoma, a malignant tumor derived from trophoblasts, is known to be highly angiogenic and metastatic. However, the molecular mechanism underlying angiogenesis in choriocarcinoma pathogenesis remains unclear. We aimed to investigate the mRNA expression and DNA methylation status of the FLT1 gene in human choriocarcinoma cells and trophoblast cells. Methods qRT-PCR, Western blotting and ELISA were conducted to evaluate the mRNA and protein expression levels of sFLT1. 5-aza-2′-deoxycytidine (5azadC) treatment and bisulfite sequencing were used to study the FLT1 gene promoter methylation. The effect of sFLT1 on choriocarcinoma growth and angiogenesis was evaluated in a xenograft mouse model. Results Expression of the FLT1 gene was strongly suppressed in choriocarcinoma cell lines compared with that in the primary trophoblasts. Treatment of choriocarcinoma cell lines with 5azadC, a DNA methyltransferase inhibitor, markedly increased in mRNA expression of three FLT1 splice variants and secretion of sFLT1 proteins. Bisulfite sequencing revealed that the CpG hypermethylation was observed at the FLT1 promoter region in choriocarcinoma cell lines and a human primary choriocarcinoma tissue but not in human trophoblast cells. Interestingly, in 5azadC-treated choriocarcinoma cell lines, sFLT1 mRNA expression and sFLT1 production were further elevated by hypoxic stimulation. Finally, as expected, sFLT1-expressing choriocarcinoma cells implanted into nude mice showed significantly slower tumor growth and reduced microvessel formation compared with GFP-expressing control choriocarcinoma cells. Conclusions Inhibition of sFLT1 production by FLT1 silencing occurs via the hypermethylation of its promoter in choriocarcinoma cells. The stable expression of sFLT1 in choriocarcinoma cells resulted in the suppression of tumor growth and tumor vascularization in vivo. We suggest that the FLT1 gene may be a cell-type-specific tumor suppressor in choriocarcinoma cells.

Aim Although the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy. Methods Thirty-two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow-up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo-cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut-off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis. Results Cervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow-up period. Conclusion Our proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.

Cervical intraepithelial neoplasia (CIN) has a natural history of bidirectional transition between different states. Therefore, conventional statistical models assuming a unidirectional disease progression may oversimplify CIN fate. We applied a continuous-time multistate Markov model to predict this CIN fate by addressing the probability of transitions between multiple states according to the genotypes of high-risk human papillomavirus (HPV). This retrospective cohort comprised 6022 observations in 737 patients (195 normal, 259 CIN1, and 283 CIN2 patients at the time of entry in the cohort). Patients were followed up or treated at the University of Tokyo Hospital between 2008 and 2015. Our model captured the prevalence trend satisfactory, particularly for up to two years. The estimated probabilities for 2-year transition to CIN3 or more were the highest in HPV 16-positive patients (13%, 30%, and 42% from normal, CIN1, and CIN2, respectively) compared with those in the other genotype-positive patients (3.1%&ndash, 9.6%, 7.6%&ndash, 16%, and 21%&ndash, 32% from normal, CIN1, and CIN2, respectively). Approximately 40% of HPV 52- or 58-related CINs remained at CIN1 and CIN2. The Markov model highlights the differences in transition and progression patterns between high-risk HPV-related CINs. HPV genotype-based management may be desirable for patients with cervical lesions.

Background Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1), a histone methyltransferase, has been found to be upregulated and its expression to be correlated with expression of enhancer of zeste homolog 2 (EZH2) in several cancers. In this study, we evaluated the role of WHSC1 and its therapeutic significance in ovarian clear cell carcinoma (OCCC). Methods First, we analyzed WHSC1 expression by quantitative PCR and immunohistochemistry using 23 clinical OCCC specimens. Second, the involvement of WHSC1 in OCCC cell proliferation was evaluated by MTT assays after siRNA-mediated WHSC1 knockdown. We also performed flow cytometry (FACS) to address the effect of WHSC1 on cell cycle. To examine the functional relationship between EZH2 and WHSC1, we knocked down EZH2 using siRNAs and checked the expression levels of WHSC1 and its histone mark H3K36m2 in OCCC cell lines. Finally, we checked WHSC1 expression after treatment with the selective inhibitor, GSK126. Results Both quantitative PCR and immunohistochemical analysis revealed that WHSC1 was significantly overexpressed in OCCC tissues compared with that in normal ovarian tissues. MTT assay revealed that knockdown of WHSC1 suppressed cell proliferation, and H3K36me2 levels were found to be decreased in immunoblotting. FACS revealed that WHSC1 knockdown affected the cell cycle. We also confirmed that WHSC1 expression was suppressed by EZH2 knockdown or inhibition, indicating that EZH2 is upstream of WHSC1 in OCCC cells. Conclusions WHSC1 overexpression induced cell growth and its expression is, at least in part, regulated by EZH2. Further functional analysis will reveal whether WHSC1 is a promising therapeutic target for OCCC. Electronic supplementary material The online version of this article (10.1186/s12885-019-5638-9) contains supplementary material, which is available to authorized users.

Renal hypouricemia is associated with urinary calculi and severe acute renal failure after exercise. The epidemiology of renal hypouricemia is not yet sufficiently understood, and there is no report of it occurring during pregnancy. We report the case of a pregnant woman with renal hypouricemia. At her first pregnancy, she developed preeclampsia with severe features at the 34th week of gestation. After parturition, she developed acute renal failure and was diagnosed with renal hypouricemia. During the second pregnancy, when she was referred to our hospital, care was taken to ensure adequate hydration by infusion of liquids and water at the time of labour. Consequently, she did not have onset of renal hypouricemia. We suggest that acute renal failure may be avoided in pregnant women with renal hypouricemia by preventing dehydration via drinking enough during pregnancy postpartum period and by infusion during labour.

Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer., The tumor microenviroment can influence cancer progression and response to therapy. In this study, the authors show that miR21 is transferred through exosomes from cancer-associated fibroblasts and adipocytes to ovarian cancer cells where it modulates drug resistance by its direct target APAF1.

The histone methyltransferase SETD8, which methylates the lysine 20 of histone H4 (H4K20), is reportedly involved in human carcinogenesis along with nonhistone proteins such as p53. However, its expression profiles and functions in the context of high-grade serous ovarian carcinoma (HGSOC) are still unknown. The purpose of this study was to investigate the role of SETD8 in HGSOC. We performed quantitative real-time PCR and immunohistochemistry to detect the expression of SETD8 in HGSOC samples and normal ovarian specimens. Then, we assessed the effect of the inhibition of SETD8 expression using small interfering RNA (siRNA) and a selective inhibitor (UNC0379) on cell proliferation and apoptosis in HGSOC cells. The expression of SETD8 was significantly upregulated in clinical ovarian cancer specimens compared to that in the corresponding normal ovary. In addition, suppression of SETD8 expression in HGSOC cells with either siRNA or UNC0379 resulted in reduced levels of H4K20 monomethylation, inhibition of cell proliferation, and induction of apoptosis. Furthermore, UNC0379 showed a long-term antitumor effect against HGSOC cells, as demonstrated by colony-formation assays. SETD8 thus constitutes a promising therapeutic target for HGSOC, warranting further functional studies.

The purpose of this retrospective study was to evaluate the usefulness of serum tumour markers and morphological characteristics in CT/MRI to differentiate between ovarian metastases from colorectal carcinomas (OMCRC) and primary ovarian carcinomas (POC).Preoperative radiological images of 41 OMCRCs from 27 patients (mean age ± SD: 52.2 ± 10.7 years) and 46 POCs from 36 patients (52.1 ± 12.7 years) were included. Three blinded gynecological radiologists classified tumour morphology into 'mille-feuille sign', 'solid and cystic', 'multicystic without nodules', and 'multicystic with nodules' groups and analysed using Fisher's exact test. Serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and carbohydrate antigen 19-9 levels were compared by Wilcoxon rank-sum test.'Mille-feuille sign' indicated OMCRC (OMCRC: 8/41, POC: 1/46, specificity = 0.98, p = 0.011) and had excellent interobserver agreement (Fleiss's kappa value = 0.96). 'Solid and cystic' indicated POC (18/41 vs 41/45, p0.001) and 'multicystic without nodules' indicated OMCRC (8/41 vs 2/46, p = 0.041). There was no significant difference in 'multicystic with nodules'. CA125 levels were higher in POCs (292.5 U/mL vs. 41.0 U/mL, p = 0.003). CEA levels were higher in OMCRCs (24.5 ng/mL vs 2 ng/mL, p0.001). CEA (6.3 ng/mL) AND (CA125 (≥87.0 U/mL) OR 'solid and cystic') indicated POC with high accuracy (3/41 vs 44/46, accuracy = 0.94, p0.001).Our new method with morphological classification and tumour markers were useful for differentiating the two tumours. In particular, the 'mille-feuille sign' frequently indicated OMCRC with high specificity and excellent interobserver agreement.

The management of refractory ascites in advanced ovarian cancer (AOC) is vital for patients with abdominal distention, respiratory distress, and anorexia due to massive ascites with cancer peritonitis. We analyzed the benefits of concentrated ascites reinfusion therapy (CART) in the management of AOC. We reviewed records of AOC patients who underwent CART between January 2011 and March 2017. We retrospectively analyzed patients’ backgrounds and physiological changes, including body weight, abdominal girth, urine volume, blood component values, blood pressure, heart rate, and body temperature before and after CART. We investigated the clinicopathological significance of CART by measuring the mean number of ascites tumor cell (ATC) clusters before CART. A retrospective analysis was performed on 29 cases of AOC with massive ascites involving 47 CART sessions. The patients’ mean age was 56.6 ± 12.8 years, and the mean number of sessions was 1.7 ± 1.2. The mean volume of the processed ascites was 2,937 ± 820 mL, which was concentrated to 272 ± 84 mL containing 85.0 ± 33.2 g protein on average. Significant reductions in abdominal girth (− 5.30 ± 0.65 cm; p

Aim The purpose of our study is to investigate clinically significant prognostic factors at the time of interval surgery (IS), comprising interval look surgery and interval debulking surgery, for T3c (International Federation of Gynecology and Obstetrics stage IIIc to IV) advanced ovarian cancer (AOC) patients during primary treatment. Methods We reviewed records of patients with T3c AOC who underwent IS following neoadjuvant chemotherapy or up-front primary debulking surgery with adjuvant chemotherapy at our institution between January 1996 and December 2010. For analysis of prognostic factors, cytology of peritoneal exfoliative cells at IS was added to clinicopathological variables. Results A retrospective analysis was performed on 50 cases. The median age was 61.1 years (range, 38–78), with median follow-up of 45.9 months (range, 12–122). Macroscopic tumors were completely resected in 32 cases (64%) at IS. Univariate analyses of clinicopathological factors for IS identified preoperative serum cancer antigen-125 levels (≥20 IU/mL; P = 0.0539), number of residual lesions at IS (≥20; P = 0.0554), incomplete surgery at IS (P = 0.0171) and positive peritoneal cytology at IS (P = 0.0015) as significant factors for prognosis regarding progression-free survival (PFS). Multivariate analysis identified positive peritoneal cytology (P = 0.0303) as a unique independent predictor of poor prognosis in PFS. Conclusion Positive peritoneal cytology at IS appears to be a significant factor for poor prognosis in PFS, which may provide useful information for post-IS chemotherapy planning. IS in the treatment of AOC may be useful for not only complete resection, but also for identification of patients with poor prognosis.

Aim The purpose of our study was to evaluate the efficacy of laser ablation as a conservative treatment for cervical intraepithelial neoplasia 3 (CIN3) and assess whether the human papillomavirus (HPV) test is useful to predict recurrence after treatment. Materials and Methods A total of 134 patients who received laser ablation for treatment of CIN3 were enrolled in this study. During the follow-up period, patients were followed with cytological and colposcopic evaluations. Recurrence of CIN3 was regarded as the primary end-point. HPV genotype was tested before and after treatment. Post-treatment cumulative recurrence rates were estimated and comparisons by both patient age and HPV genotype were performed. Results Overall cumulative recurrence rate of CIN3 in the first year after treatment was 22.6% for all patients. No significant correlation was shown between patient age and recurrence. Patients infected by specific genotypes (16, 18, 31, 33, 52, and 58) frequently failed to clear the infection after treatment. The 1-year recurrence-free survival in those positive after treatment for eight high-risk genotypes (16, 18, 31, 33, 35, 45, 52, and 58) was significantly lower (66.7%), compared to that in those positive for other high-risk types (78.6%). The recurrence-free survival of those who remained HPV-positive after treatment was significantly lower than those who turned negative. Conclusion Laser ablation should be performed prudently with appropriate patient counseling about recurrence rate. Considering its minimal invasiveness, laser ablation is effective, especially for young patients who are negative for eight high-risk genotypes. With regard to HPV testing, although genotyping has significant value for predicting recurrence, screening for all genotypes warrants further evaluation.

Background: The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams–Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date. Methods: A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated. Results: We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1. Conclusion: These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.

The aim of the present study was to evaluate whether measuring endometrial thickness during fertility-sparing treatment with medroxyprogesterone acetate (MPA) can be a predictive marker for effectiveness in women with endometrioid adenocarcinoma, grade 1 (EmCa, G1). A total of 32 patients with stage IA EmCa, G1 underwent treatment with MPA. Patients were 5 mm at week 16 was an independent factor for prediction of non-CR. Measurement of endometrial thickness during MPA treatment may be useful as a predictive marker for pathological response to MPA in patients with EmCa, G1.

Although many studies have already shown that lymph node metastasis is one of the major prognostic factors for cervical cancer, the therapeutic significance of para-aortic lymphadenectomy for the surgical treatment of cervical cancer remains controversial. A total of 308 patients diagnosed with stage IB2, IIA2, or IIB cervical cancer and treated with radical hysterectomy were retrospectively investigated to assess the incidence of para-aortic lymph node metastasis and the clinicopathological factors linked to cervical cancer prognosis. Para-aortic lymph node metastases were pathologically confirmed in 13 of the 136 patients (9.6 %) who underwent para-aortic lymphadenectomy. The incidence of para-aortic lymph node metastasis was significantly higher in the patients who had common iliac lymph node metastases (odds ratio 31.5, p

Surgery is effective and useful for curative treatment of patients with early invasive cervical cancer, yet minimization of surgical procedures provides many additional advantages for patients. Because the mean age of patients diagnosed with cervical precancer and invasive cancer has been decreasing, the need for minimization of surgery to reduce disruption of fertility is increasing. Trachelectomy is an innovative procedure for young patients with invasive cancer. Minimally invasive procedures are increasingly implemented in the treatment of patients with early cervical cancer, such as laparoscopic/robotic surgery and sentinel lymph node navigation. The use of modified radical hysterectomy may not only be curative but also minimally invasive for Stage IA2-IB1 patients with a tumor size

Most ovarian cancers are diagnosed at an advanced stage when the tumor is widely metastatic. The 5-year survival drops to 50% for the cancer cases that spread beyond the pelvis to the omentum. However, the mechanisms underlying the effect of omental adipose tissue on ovarian cancer progression are poorly understood. Recent studies showed that exosomes also contain non-coding RNAs such as microRNAs (miRNAs). Thus, we hypothesize that the transfer of microRNAs and their variants from ovarian cancer-associated omental adipose tissues to ovarian cancer cells via exosomes may contribute to the nearby microenvironment for ovarian cancer metastasis and cancer progression. Ion Torrent next generation sequencing was performed on miRNAs isolated and enriched from exosomes and cell lysates of ovarian cancer cell lines (OVCA), the epithelial component of microdissected omental ovarian cancer tissues (CT), normal omental adipose tissues (OMN) and ovarian cancer-associated omental adipose tissues (OMT). By integrating the miRNA expression profiles, 65 miRNAs were expressed at significant higher levels in OMT-derived exosomes compared with those in OMN-derived exosomes and OVCA-derived exosomes. A set of miRNAs (miR-32a, miR-221 and miR320a), which had been implicated in controlling cell growth and chemoresistance, was identified. Also, the Ion Torrent results were validated and exosomal transfer of OMT-derived miRNAs was confirmed in vitro. The exosomal communication between adipose tissues and ovarian cancer cells in the omental tumor microenvironment is verified. The transferable miRNAs and their variants may remain functional in the recipient ovarian cancer cells and confer more aggressive phenotypes in these cells. Citation Format: Chi Lam Au Yeung, Tetsushi Tsuruga, Ngai Na Co, Tsz-Lun Yeung, Cecilia S. Leung, Kwong K. Wong, Samuel C. Mok. Adipose tissues derived exosomal microRNAs and their variants in ovarian cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 715.

Mutation of neoplastic tumor suppressor genes, scribble, discs large, and lethal giant larvae (Igl), causes disruption of cell polarity and overproliferation of Drosophila epithelial cells and neuroblasts. Reduced expression of human homologue of Igl, Hugl-1, has been reported to be involved in development and progression of human colon cancer and malignant melanoma. To explore the association between Hugl-1 expression and clinical character in endometrial cancer, we examined the expression of Hugl-1 in primary endometrial cancer tissues. The expression of Hugl-1 mRNA in 86 primary endometrial cancer tissues was examined using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). All samples were categorized into two groups: Hugl-1 positive and Hugl-1 negative. Clinical data of each group were analyzed by Fisher's exact probability test and survival rates of each group were compared by Kaplan-Meier method and Log-rank test. Loss of Hugl-1 expression had correlation with the higher incidence of lymph node metastasis, but not to the patient's age at onset, distant metastasis, clinical stage, lymph or venous vessel invasion, or histopathological grade of differentiation. The Hugl-1 -positive group had poorer prognosis compared with the Hugl-1-negative group. These results indicate that loss of Hugl-1 expression in endometrial cancer may contribute to lymph node metastasis and it can be a factor of poor prognosis.

Ovarian cancer is the most common cause of gynecologic malignancy related mortality in women. The combination of tumor reductive surgery and chemotherapy is the main therapeutic strategy for ovarian cancer. However, especially in the most of advanced cases, complete site reduction is impossible to achieve. In those cases, the sensitivity to chemotherapy strongly affects their prognoses. MicroRNAs (miRNAs), which are approximately 22-nucleotide non-coding RNAs, regulate protein expression by translational inhibition and degradation of their target mRNAs. The expression of miRNAs is dysregulated in various types of cancers, suggesting that miRNAs are involved in carcinogenesis and cancer progression. The purpose of present work was to identify miRNAs which are related to chemo-sensitivity in ovarian cancer. Using Next Generation Sequencing (NGS), miRNA profiling was performed in 38 advanced high-grade serous ovarian cancers (HGSOCs). RNAs including miRNAs were procured from the epithelial component of the laser microdissected tumor tissue removed from patients undergoing primary surgery without neo-adjuvant chemotherapy. A total of 1935 miRNAs and miRNA variants were detected by NGS and normalized expression data of each miRNAs and miRNA variants were used for further analyses. Comparing the copy numbers of each miRNAs between chemo-refractory group (patients with disease progression in the period of first line chemotherapy, n=7) and chemo-sensitive group (patients with disease progression in more than 6 months after completion of first line chemotherapy, n=13) by Mann-Whitney U test, 77 miRNAs and miRNA variants were found to be dysregulated with significant differences (p Our results strongly suggest that mir-625-3p might be a prognostic marker that can be used to predict chemo-sensitivity in patients with HGSOC. Further characterization of mir-625-3p as a therapeutic target for HGSOC is in progress. Citation Format: Tetsushi Tsuruga, Chi Lam Au Yeung, Cecilia S. Leung, Tsz-Lun Yeung, Kwong K. Wong, Rosemarie Schmandt, Ngai Na Co, Karen H. Lu, Samuel Mok. Identification of microRNAs related to chemosensitivity in ovarian cancer using Next Generation Sequencing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1939. doi:10.1158/1538-7445.AM2013-1939