Significance of positive peritoneal cytology for recurrence and survival in patients with endometrial cancer.

AIM: This study aims to examine the association between malignant peritoneal cytology and prognosis in women with endometrial cancer. METHODS: We retrospectively analyzed the records of patients with endometrial cancer who underwent surgery with intraoperative peritoneal cytology at our hospital between January 1988 and December 2012. All results were reclassified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) system, and the relation between intraoperative peritoneal cytology results and recurrence and prognosis was examined. RESULTS: Of the 908 patients analyzed, 205 (22.6%) had positive peritoneal cytology. Patients with positive peritoneal cytology had significantly lower rates of recurrence-free survival (RFS) and overall survival (OS) than those in the negative cytology group (both p < 0.001). Subgroup analysis of patients with FIGO stage I/II showed significantly lower RFS in the positive-cytology group (p = 0.005), but there was no significant difference in OS (p = 0.637). In the patients with FIGO stage III/IV or patients classified as "high risk," the RFS and OS were significantly lower in the positive-cytology group (both p < 0.001). Cox regression analysis identified positive peritoneal cytology as a significant predictor of recurrence in patients with FIGO stage I/II disease. CONCLUSIONS: Patients with positive peritoneal cytology for endometrial cancer have a high risk of recurrence, regardless of histopathologic type or FIGO stage. Peritoneal cytology has already been removed from the 2009 FIGO classification of endometrial cancer, but it may deserve reconsideration.

Questionnaire survey regarding current status of minimally invasive surgery for endometrial cancer in Japan: A cross-sectional survey for JSGOE members.

AIM: Minimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross-sectional questionnaire survey to ascertain the status of MIS for endometrial cancer. METHODS: The survey was conducted between May 10 and June 30, 2022. The questionnaire included information on personal attributes, academic affiliations, qualifications, hysterectomies, and intraoperative procedures performed. RESULTS: The total number of questionnaire respondents was 436 (9.2% of the membership). The hysterectomy methods and percentage performed were as follows: simple total hysterectomy (equivalent to benign surgery), 3%; simple total hysterectomy with care to avoid shaving the cervix, 31%; extended total hysterectomy, 48%; and modified radical hysterectomy, 15%. An analysis of hysterectomies performed using MIS for endometrial cancer by qualified gynecologists of endoscopy or board-certified gynecologic oncologists showed a tendency not to choose simple total hysterectomy compared to the gynecologists who did not hold certification (p = 0.019, p = 0.045, and p = 0.010, respectively). Additionally, 67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan. CONCLUSION: This study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra-fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS.

Ceramide synthase 2-C24:1 -ceramide axis limits the metastatic potential of ovarian cancer cells.

Regulation of sphingolipid metabolism plays a role in cellular homeostasis, and dysregulation of these pathways is involved in cancer progression. Previously, our reports identified ceramide as an anti-metastatic lipid. In the present study, we investigated the biochemical alterations in ceramide-centered metabolism of sphingolipids that were associated with metastatic potential. We established metastasis-prone sublines of SKOV3 ovarian cancer cells using an in vivo selection method. These cells showed decreases in ceramide levels and ceramide synthase (CerS) 2 expression. Moreover, CerS2 downregulation in ovarian cancer cells promoted metastasis in vivo and potentiated cell motility and invasiveness. Moreover, CerS2 knock-in suppressed the formation of lamellipodia required for cell motility in this cell line. In order to define specific roles of ceramide species in cell motility controlled by CerS2, the effect of exogenous long- and very long-chain ceramide species on the formation of lamellipodia was evaluated. Treatment with distinct ceramides increased cellular ceramides and had inhibitory effects on the formation of lamellipodia. Interestingly, blocking the recycling pathway of ceramides by a CerS inhibitor was ineffective in the suppression of exogenous C24:1 -ceramide for the formation of lamellipodia. These results suggested that C24:1 -ceramide, a CerS2 metabolite, predominantly suppresses the formation of lamellipodia without the requirement for deacylation/reacylation. Moreover, knockdown of neutral ceramidase suppressed the formation of lamellipodia concomitant with upregulation of C24:1 -ceramide. Collectively, the CerS2-C24:1 -ceramide axis, which may be countered by neutral ceramidase, is suggested to limit cell motility and metastatic potential. These findings may provide insights that lead to further development of ceramide-based therapy and biomarkers for metastatic ovarian cancer.

MicroRNA-152 Regulates Endometrial Serous Carcinoma Cell Motility by Suppressing Matrix Metalloproteinase 10 Expression.

MicroRNA-152 (miR-152) expression has been reported to be associated with poor prognosis in patients with endometrial serous carcinoma (ESC). However, the function of miR-152 in ESCs is not fully understood. The present study aimed to investigate the involvement of miR-152 in ESC progression. The influence of miR-152 overexpression on cell proliferation and motility was assessed by transfecting two human ESC cell lines, USPC-1 and SPAC-1-L, with a miR-152 precursor. MiR-152 overexpression increased apoptosis and inhibited the proliferation of the two ESC cell lines. Cell motility was also suppressed in both cell lines following precursor transfection. Conversely, miR-152 inhibitor transfection led to an increase in cell migration ability, suggesting the involvement of miR-152 in ESC cell motility. Results of the analysis of publicly available messenger RNA dataset indicated that high expression of matrix metalloproteinase 10 (MMP10), one of the predicted targets of miR-152 by microRNA target prediction database, was a poor prognostic factor for ESC. In vitro examination results revealed that miR-152 overexpression reduced MMP10 expression, and knockdown of MMP10 significantly reduced cell motility. This study elucidates the function of miR-152 as a tumor suppressor in ESCs. We demonstrated that miR-152 plays an important role in ESC cell motility by regulating MMP10 expression.

A Single Arm Prospective Pilot Study Examining the Efficacy and Safety of Bevacizumab Single Maintenance Therapy Following Platinum-Based Chemotherapy in Patients with Advanced or Recurrent Cervical Cancer.

Although the addition of bevacizumab to platinum-based combination chemotherapy has been recommended as a standard regimen for patients with advanced or recurrent cervical cancer, there is no clear evidence regarding the effectiveness of bevacizumab monotherapy as salvage chemotherapy. This study prospectively examined the efficacy and safety of switching from platinum-based chemotherapy combined with bevacizumab to single maintenance therapy in patients with advanced or recurrent cervical cancer. Patients were first treated with standard combination chemotherapy. However, if chemotherapy was discontinued because of an adverse event, bevacizumab monotherapy was continued for patients who agreed to participate in this study and provided written informed consent. The study protocol was approved by the Independent Review Board of Tohoku University School of Medicine (reception number 2017-1-540). A total of 15 patients (median age of 55 years, range 33-69 years) participated in this study. The median number of cycles of bevacizumab single maintenance administration was 8, and the main reasons for discontinuation were disease progression and adverse events. Bevacizumab single maintenance therapy had a disease control rate of 53.3% (CR 40%, PR 6.7%, SD 6.7%). The most frequent grade 3/4 clinical adverse events were proteinuria (5/15) and hypertension (4/15). No treatment-related deaths occurred. Bevacizumab single maintenance therapy was effective as salvage chemotherapy in patients with advanced or recurrent cervical cancer, and the safety profile was generally consistent with those reported in previous studies of bevacizumab monotherapy.

La-Related Protein 4 as a Suppressor for Motility of Ovarian Cancer Cells.

The La-related proteins (LARPs) are a family of RNA binding proteins that control the degradation and stabilization of RNAs. As emerging research reveals the biology of each LARP, it is evident that LARPs are dysregulated in some types of cancer. Upregulation of cell motility potentiates the metastatic potential of ovarian cancer cells; however, the roles of LARPs in cell motility remain unknown. In the present study, we investigated the roles of LARPs in the progression of ovarian cancer using SKOV3 human ovarian cancer cells and a public database that integrates microarray-based gene expression data and clinical data. To explore the involvement of LARPs in the cell motility, we performed RNA interference screening for LARP mRNAs in SKOV3 cells. The screening identified LARP4 as a potential suppressor of the formation of lamellipodia. Conversely, enforced expression of LARP4 suppressed the formation of lamellipodia. Moreover, cell migration was significantly increased in LARP4-depleted SKOV3 cells. Mechanistically, LARP4 depletion was associated with the decrease in RhoA protein expression. These results suggest that LARP4 may limit RhoA-dependent cell motility. In a mouse xenograft model with SKOV3 cells, LARP4 depletion potentiated peritoneal metastasis. Upon analysis of a public database of patients with ovarian cancer, the LARP4 mRNA-high expression group (n = 166) showed longer overall survival compared with the LARP4 mRNA-low expression group (n = 489), implying a positive correlation of LARP4 mRNA levels in ovarian cancer tissues with patient prognosis. Taken together, we propose that LARP4 could suppress motility and metastatic potential of ovarian cancer cells.

Cytokeratin 7-positive/cytokeratin 20-negative cecal adenocarcinoma metastatic to the uterine cervix: a case report.

BACKGROUND: The vast majority of uterine cervical malignancies are primary carcinomas, and secondary neoplasms that metastasize to the uterine cervix from a distant organ are uncommon. Although relatively rare, metastases to the uterine cervix from a primary colon cancer have been reported. We report a rare case of metastatic carcinoma originating from a cecal adenocarcinoma with an unusual cytokeratin 7/cytokeratin 20 immunophenotype. CASE PRESENTATION: A 74-year-old postmenopausal Japanese woman was referred to our hospital for the evaluation of a uterine tumor. She had a past medical history of cecal cancer and had undergone laparoscopically assisted right hemicolectomy at the age of 69 years. During follow-up, she was found to have elevated levels of the tumor markers carbohydrate antigen 19-9 (179.7 IU/mL) and carcinoembryonic antigen (26.9 µg/L). Positron emission tomography/computed tomography showed a focus of high 18F-fluorodeoxyglucose uptake in her uterus. Examination of a cervical biopsy found a poorly differentiated adenocarcinoma that was immunopositive for cytokeratin (CK)7 and caudal-related homeobox 2 (CDX2) expression and immunonegative for cytokeratin 20 expression. The patient underwent radical hysterectomy and bilateral salpingo-oophorectomy. Histopathological examination found invasive growth of irregular and atypical ductal hyperplasia. Immunohistochemical staining of the tumor specimen revealed the same immunophenotype as the biopsy specimen. The cecal cancer specimen from her previous surgery was also examined and found to have the same immunophenotype. The histopathological diagnosis was cecal adenocarcinoma metastatic to the uterine cervix. The patient is currently receiving adjuvant chemotherapy and to date is without evidence of recurrent disease. CONCLUSIONS: Our report illustrates the importance of immunohistochemistry for the correct diagnosis of the origin of a uterine cervical adenocarcinoma in a patient with a medical history of colorectal cancer. Re-examination of a previous oncological specimen is critical for cases with a uterine lesion that is difficult to identify as primary or metastatic cancer.

Outcomes of abdominal radical trachelectomy: results of a multicenter prospective cohort study in a Tohoku Gynecologic Cancer Unit.

BACKGROUND: This study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer. METHODS: This was a multicenter prospective cohort study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients with FIGO 1A-1B1 squamous cell carcinoma were included. RESULTS: A total of 42 patients were registered in this study, and all patients underwent planned RAT. The median stromal invasion and median horizontal spread of resected specimens were 4.6 (range 1.0-10.0) and 12.4 mm (range 3.0-28.0), respectively. The median surgical time and median blood loss were 304 min (range 233-611) and 848 mL (range 250-3984), respectively. Five patients (11.9 %) received blood transfusion. Five of 18 (27.8 %) patients who attempted to conceive achieved pregnancy, and 3 patients had healthy babies. However, all pregnancies required assisted reproductive technology with in-vitro fertilization and embryo transfer. Four patients (9.5 %) received postoperative adjuvant therapy, and 3 patients (7.1 %) developed disease recurrence. CONCLUSIONS: RAT may be safely performed for Japanese patients with FIGO 1A-1B1 squamous cell carcinoma of the cervix, even in educational medical facilities. However, less-invasive surgery should be considered more often to improve pregnancy outcomes.

Evaluation of postoperative chemotherapy in patients with uterine carcinosarcoma: a retrospective survey of the Tohoku Gynecologic Cancer Unit.

BACKGROUND: The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma. METHODS: We conducted a retrospective survey of seven medical facilities in the Tohoku Gynecologic Cancer Unit. RESULTS: A total of 45 patients who had undergone hysterectomy and bilateral salpingo-oophorectomy were enrolled. No significant difference was observed in overall survival according to patient age (≤ 50 years vs >50 years) or retroperitoneal lymphadenectomy (performed vs. not performed). However, the International Federation of Gynecology and Obstetrics stage (stage I/II vs stage III/IV) and postoperative chemotherapy (provided vs not provided) were significant prognostic factors in both univariate and multivariate analyses for the 25-month median follow-up period. CONCLUSIONS: Our results revealed that postoperative chemotherapy should be considered for all uterine carcinosarcoma stages in Japanese patients.

Functional genomics identifies therapeutic targets for MYC-driven cancer.

MYC oncogene family members are broadly implicated in human cancers, yet are considered "undruggable" as they encode transcription factors. MYC also carries out essential functions in proliferative tissues, suggesting that its inhibition could cause severe side effects. We elected to identify synthetic lethal interactions with c-MYC overexpression (MYC-SL) in a collection of ~3,300 druggable genes, using high-throughput siRNA screening. Of 49 genes selected for follow-up, 48 were confirmed by independent retesting and approximately one-third selectively induced accumulation of DNA damage, consistent with enrichment in DNA-repair genes by functional annotation. In addition, genes involved in histone acetylation and transcriptional elongation, such as TRRAP and BRD4, were identified, indicating that the screen revealed known MYC-associated pathways. For in vivo validation we selected CSNK1e, a kinase whose expression correlated with MYCN amplification in neuroblastoma (an established MYC-driven cancer). Using RNAi and available small-molecule inhibitors, we confirmed that inhibition of CSNK1e halted growth of MYCN-amplified neuroblastoma xenografts. CSNK1e had previously been implicated in the regulation of developmental pathways and circadian rhythms, whereas our data provide a previously unknown link with oncogenic MYC. Furthermore, expression of CSNK1e correlated with c-MYC and its transcriptional signature in other human cancers, indicating potential broad therapeutic implications of targeting CSNK1e function. In summary, through a functional genomics approach, pathways essential in the context of oncogenic MYC but not to normal cells were identified, thus revealing a rich therapeutic space linked to a previously "undruggable" oncogene.

Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer.

BACKGROUND: Pelvic exenteration has attained an important role in the treatment of advanced or recurrent cervical cancer for obtaining a complete cure or longer disease-free survival. The purpose of this study was to evaluate patients undergoing pelvic exenteration and to determine the clinical features associated with outcome and survival. METHODS: We retrospectively analyzed the records of 12 patients who underwent pelvic exenteration for uterine cervical cancer between July 2002 and August 2011. RESULTS: Two patients had primary stage IVA cervical adenocarcinoma and 10 patients had recurrent cervical cancer. Eight patients underwent anterior pelvic exenteration, 3 patients underwent total pelvic exenteration, and 1 patient underwent posterior pelvic exenteration. With a median duration of follow-up of 22 months (range 3-116 months), 5 patients were alive without recurrence. Of 5 patients with no evidence of disease, 4 were recurrent or residual tumor, all of whom had common factors, such as a tumor size ≤ 30 mm, negative surgical margins, complete resection, and no lymph node involvement. The 5-year overall survival rate for 12 patients was 42.2 %. Ileus was the most common complication (42 %) and post-operative intestinal anastomosis leaks developed in 3 patients, but no ureteral anastomosis leaks occurred. CONCLUSIONS: Pelvic exenteration is a feasible surgical procedure in advanced and/or recurrent cervical cancer patients with no associated post-operative mortality, and the only therapeutic option for complete cure or long-term survival; however, post-operative complications frequently occur.

Feasibility study of gemcitabine plus docetaxel in advanced or recurrent uterine leiomyosarcoma and undifferentiated endometrial sarcoma in Japan.

BACKGROUND: Uterine leiomyosarcoma (LMS) and undifferentiated endometrial sarcoma (UES) are rare, aggressive malignancies. Both are treated similarly; however, few chemotherapy agents are effective. Recently, the combination of gemcitabine (900 mg/m(2), days 1 and 8) plus docetaxel (100 mg/m(2), day 8) with granulocyte colony-stimulating factor (G-CSF, 150 µg/m(2), days 9-15) has been shown to have activity in LMS. In Japan, neither prophylactic G-CSF at a dose of 150 µg/m(2) nor docetaxel at a dose of 100 mg/m(2) are approved for use. For this reason, we evaluated the combination of 900 mg/m(2) gemcitabine plus 70 mg/m(2) docetaxel regimen without prophylactic G-CSF support in advanced or recurrent LMS and UES in Japanese patients. METHODS: Eligible women with advanced or recurrent LMS and UES were treated with 900 mg/m(2) gemcitabine on days 1 and 8, plus 70 mg/m(2) docetaxel on day 8, every 3 weeks. The primary endpoint was overall response rate, defined as a complete or partial response. RESULTS: Of the eleven women enrolled, 10 were evaluated for a response. One complete response and 2 partial responses were observed (30 %) with an additional 4 (40 %) having stable disease. Mean progression-free survival was 5.4 months (range 1.3-24.8 months), and overall survival was 14 months (range 5.3-38.4 months). Grade 4 neutropenia was the major toxicity (50 %). The median number of cycles was 5 (range 2-18). Twenty-two cycles (44 %) employed G-CSF. CONCLUSION: The gemcitabine plus docetaxel regimen without prophylactic G-CSF support was tolerable and highly efficacious in Japanese patients with advanced or recurrent LMS and UES.

Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study.

BACKGROUND: Paclitaxel and carboplatin (PC) have shown antitumor activity in carcinosarcoma of the uterus (CS). The purpose of this prospective multi-institutional study was to determine the response rate (RR), progression-free survival (PFS) and overall survival (OS) and to assess the toxicity of paclitaxel and carboplatin in patients with CS. METHODS: We conducted a phase II study in which patients were administered paclitaxel 175 mg/m(2) over a 3-h period followed by carboplatin (area under the serum concentration-time curve = 6) intravenously over a 30-min period on day 1 of each treatment cycle (3 weeks) until disease progression or adverse effects prohibited further therapy. Eligible patients had histologically confirmed, advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. RESULTS: Six patients were enrolled between February 2006 and April 2009. The median age of the patients was 61 (range 48-77) years; one patient was stage IIIC (17 %) and five were stage IVB (83 %). Three patients (50 %) (1 at stage IIIC and 2 at stage IVB) received total abdominal hysterectomy plus bilateral salpingo-oophorectomy as part of the initial treatment; five (83 %) had homologous tumors and one (17 %) had a heterologous tumor. The median cycle number administered was 4.8 (range 2-7). The RR was 66.7 % (complete response, 2; partial response, 2); the PFS was 9.1 months and OS was not reached. The frequently observed Grade 4 toxicities were neutropenia (3 patients, 50 %). Manageable neutropenic sepsis developed in one patient. CONCLUSION: This is the first prospective multi-institutional study in Asia showing that PC may be effective and tolerable for the treatment of advanced or recurrent CS.

Associations of Nutrients and Dietary Preferences with Recurrent Pregnancy Loss and Infertility.

This review examines associations of nutrients and dietary preferences with recurrent pregnancy loss (RPL), miscarriage, and infertility. Research articles, reviews, and meta-analyses of RPL and infertility that focused on nutrition, meals, and lifestyle were reviewed, and associations of nutrients and dietary preferences with pregnancy are discussed in relation to recent research findings. Studies related to RPL were given the highest priority, followed by those dealing with miscarriage and infertility. Multivitamin supplements-even when lacking folic acid or vitamin A-reduced total fetal loss. High-dose folic acid supplementation before conception reduced the risk of miscarriage and stillbirth. A meta-analysis revealed a strong association of vitamin D deficiency/insufficiency with miscarriage. Another meta-analysis revealed that seafood and dairy products reduced the risk of miscarriage, whereas a caffeine intake of 300 mg/day or more was associated with miscarriage. A balanced diet that included nutrients with antioxidant properties helped prevent miscarriage, whereas a diet that included processed foods and nutrients with proinflammatory effects increased the risk of miscarriage. Associations of nutrients with RPL warrant further research.

Feasibility of Predicting Surgical Duration in Endometriosis Using Numerical Multi-Scoring System of Endometriosis (NMS-E).

BACKGROUND: Endometriosis is a multifaceted gynecological condition that poses diagnostic challenges and affects a significant number of women worldwide, leading to pain, infertility, and a reduction in patient quality of life (QoL). Traditional diagnostic methods, such as the revised American Society for Reproductive Medicine (r-ASRM) classification, have limitations, particularly in preoperative settings. The Numerical Multi-Scoring System of Endometriosis (NMS-E) has been proposed to address these shortcomings by providing a comprehensive preoperative diagnostic tool that integrates findings from pelvic examinations and transvaginal ultrasonography. METHODS: This retrospective study aims to validate the effectiveness of the NMS-E in predicting surgical outcomes and correlating with the severity of endometriosis. Data from 111 patients at Nippon Medical School Hospital were analyzed to determine the correlation between NMS-E scores, including E-score-a severity indicator-traditional scoring systems, surgical duration, blood loss, and clinical symptoms. This study also examined the need to refine parameters for deep endometriosis within the NMS-E to enhance its predictive accuracy for disease severity. RESULTS: The mean age of the patient cohort was 35.1 years, with the majority experiencing symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. A statistically significant positive correlation was observed between the NMS-E's E-score and the severity of endometriosis, particularly in predicting surgical duration (Spearman correlation coefficient: 0.724, p < 0.01) and blood loss (coefficient: 0.400, p < 0.01). The NMS-E E-score also correlated strongly with the r-ASRM scores (coefficient: 0.758, p < 0.01), exhibiting a slightly more excellent predictive value for surgical duration than the r-ASRM scores alone. Refinements in the methodology for scoring endometriotic nodules in uterine conditions improved the predictive accuracy for surgical duration (coefficient: 0.752, p < 0.01). CONCLUSIONS: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease's severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.

Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer.

OBJECTIVE: The aim of the present study was to clarify the most effective combination of injected tracer types and injection sites in order to detect sentinel lymph nodes (SLNs) in early endometrial cancer. PATIENTS AND METHODS: The study included 100 consecutive patients with endometrial cancer treated at Tohoku University Hospital between June 2001 and December 2012. The procedure for SLN identification entailed either radioisotope (RI) injection into the endometrium during hysteroscopy (55 cases) or direct RI injection into the uterine cervix (45 cases). A combination of blue dye injected into the uterine cervix or uterine body intraoperatively in addition to preoperative RI injection occurred in 69 of 100 cases. All detected SLNs were recorded according to the individual tracer and the resultant staging from this method was compared to the final pathology of lymph node metastases including para-aortic nodes. RESULTS: SLN detection rate was highest (96%) by cervical RI injection; however, no SLNs were detected in para-aortic area. Para-aortic SLNs were detected only by hysteroscopic RI injection (56%). All cases with pelvic lymph node metastases were detected by pelvic SLN biopsy. Isolated positive para-aortic lymph nodes were detected in 3 patients. Bilateral SLN detection rate was high (96%; 26 of 27 cases) by cervical RI injection combined with dye. CONCLUSION: RI injection into the uterine cervix is highly sensitive in detection of SLN metastasis in early stage endometrial cancer. It is a useful and safe modality when combined with blue dye injection into the uterine body.

Food intake and the risk of endometrial endometrioid adenocarcinoma in Japanese women.

The present study examined the association between food intake and endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control study in Japanese women. One hundred sixty-one cases and 380 controls who completed a questionnaire regarding demographic, lifestyle, and food frequency questionnaire were analyzed. Odds ratio (OR) between selected food intakes and EEA were calculated by logistic regression analysis. After adjustment putative confounding factors, the higher intakes of vegetables [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.26-0.83], peanuts (OR = 0.48, CI = 0.27-0.86), fish (OR = 0.52, CI = 0.29-0.93), boiled egg (OR = 0.24, CI = 0.33-0.92), instant noodles (OR = 1.94, CI = 1.12-3.34), instant food items (OR = 2.21, CI = 1.31-3.74), and deep-fried foods (OR = 2.87, CI = 1.58-5.21) were associated with a risk for EEA. The inverse association with a risk of EEA was also seen in higher intakes (g/1000 kcal) for vegetables (0.45, CI = 0.25-0.81) and fish (0.53, CI = 0.30-0.94) as compare to lower intake. Higher intake of vegetables, peanuts, fish, and boiled egg was associated with a reduced risk for EEA, whereas instant noodles, instant food items, and deep-fried foods was associated with an increased risk for EAA as compared to lower levels of intake.

Small cell carcinoma of the uterine cervix: clinical outcome of concurrent chemoradiotherapy with a multidrug regimen.

Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with advanced stage disease, the response rate was 75% (complete response, 1; partial response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.

A Retrospective Study Comparing Olaparib and Bevacizumab as a Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: Impact on Recurrence-Free Survival in Japanese and Asian Populations.

The use of angiogenesis inhibitors and poly ADP-ribose polymerase inhibitors following multi-agent chemotherapy, including platinum-based agents, has become the standard treatment for platinum-sensitive recurrent ovarian cancer (PSROC). However, the optimal maintenance therapy and selection criteria for these patients remain unclear. Thus, this study aimed to optimize the treatment options and selection criteria for patients with PSROC. The clinical data of 51 patients with PSROC admitted to Nippon Medical School Chiba Hokusoh Hospital and Nippon Medical School Hospital were retrospectively collected. The log-rank test was used for the survival analysis, and Cox proportional hazard regression analysis was used for the multivariate survival analysis. Of the 51 patients, 17 received maintenance therapy with bevacizumab (Bev), and 34 received olaparib (Ola). Recurrence-free survival (RFS) was significantly prolonged in the Ola group (27 months; 95% confidence interval (CI), 19-NA months) compared with that in the Bev group (9 months; 95% CI, 5-22 months; p = 0.000103). The efficacy of Ola was independent of background factors, including response to previous chemotherapy, homologous recombination status, histological type, or laboratory data. Ola is superior to Bev as PSROC maintenance therapy, especially in Japanese and Asian populations.

Preoperative screening endometrial cytology discovered incidental gynaecological malignancy in two patients undergoing risk-reducing salpingo-oophorectomy.

Pelvic ultrasonography and measurement of serum cancer antigen 125 (CA-125) are recommended for preoperative evaluation before performing risk-reducing salpingo-oophorectomy (RRSO). We report our experience with two patients in whom an incidental gynaecological malignancy was found using endometrial cytology as a preoperative screening test for RRSO. Patient 1 was an early 50s woman with a pathologic variant of BRCA1 Transvaginal ultrasonography showed no endometrial abnormalities, but preoperative endometrial cytology revealed high-grade serous carcinoma. The patient underwent total hysterectomy, bilateral adnexectomy, pelvic and para-aortic lymph node dissection, and omentectomy. Patient 2 was a late 40s woman with a pathological variant of BRCA1 Transvaginal ultrasonography showed mild enlargement of the left ovary, and her CA-125 level was elevated. Preoperative endometrial cytology revealed high-grade serous cancer. She underwent total hysterectomy, bilateral adnexectomy and omentectomy. These case reports illustrate the importance of preoperative screening-including endometrial cytology-before performing RRSO.