Tadalafil for Treatment of Fetal Growth Restriction: A Review of Experimental and Clinical Studies.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Visceral Adipose Tissue Percentage Compared to Body Mass Index as Better Indicator of Surgical Outcomes in Women With Obesity and Endometrial Cancer.

STUDY OBJECTIVE: To assess the impact visceral adipose tissue percentage (VAT%) on surgical outcomes during minimally invasive surgery in obese women with endometrial cancer. DESIGN: Retrospective observational cohort study. SETTING: Mie University Hospital, Japan. PATIENTS: Of the 73 women (body mass index [BMI] >30 kg/m2) with obesity and primary endometrial cancer, 52 underwent robotic surgery, while 21 underwent laparoscopic surgery between April 2014 and December 2022. INTERVENTIONS: We investigated the correlation between surgical outcomes (operative time and blood loss) and obesity (BMI and visceral adipose tissue percentage [VAT%]). MEASUREMENTS AND MAIN RESULTS: Abdominal fat-related parameters were measured at the level of the umbilicus using preoperative computed tomography. A weak negative correlation was found between BMI and VAT% (CC = -0.313, p = .001). Multivariate analysis showed that VAT% had a stronger correlation to total and practical operative time than BMI (ß = 0.338 vs 0.267, ß = 0.311 vs 0.209, respectively) and was an independent predictor of blood loss. VAT% was an independent predictive marker prolonged for operative time and increased blood loss during lymphadenectomy. CONCLUSION: VAT% could be an indicator of surgical outcomes for patients with obesity and endometrial cancer.

Factors for the development of anemia in patients with newly introduced olaparib: A retrospective case-control study.

Anemia is the most common dose-limiting toxicity of olaparib. However, few studies have analyzed the clinical features of olaparib-induced anemia. This study investigated the clinical features of olaparib-induced anemia. Additionally, the role of folate or vitamin B12 in olaparib-induced anemia was examined. This retrospective case-control study included patients who received olaparib at Mie University Hospital between January 2018 and December 2020. Data were collected between initiation of olaparib and discontinuation of olaparib or till December 2021. We investigated the development of grade ≥ 3 anemia during olaparib administration for at least 1 year. We examined patients with grade ≥ 3 anemia considering the mean corpuscular volume (MCV), its association with gastrointestinal events and cumulative dose of carboplatin. For the sub-study analysis, data on patients treated with olaparib for ovarian or endometrial cancer were collected to evaluate the Common Terminology Criteria for Adverse Events (CTCAE) or monthly changes in folate or vitamin B12 levels from baseline to 3 months after olaparib initiation. These data were collected between initiation of olaparib and discontinuation of olaparib or till November 2022. Patients with no data on folic acid or vitamin B12 levels were excluded from the sub-study. In the main study, 40 patients were included. Eighteen patients (45%) developed grade ≥ 3 anemia, and all patients discontinued treatment (94%) or reduced olaparib dose (67%) after developing anemia. Among the patients with grade ≥ 3 anemia, 9 (50%) exhibited macrocytic anemia and 15 (83%) had previously received carboplatin. The incidence of grade ≥ 2 dysgeusia was significantly higher in patients with grade ≥ 3 anemia (P = .034). Moreover, the cumulative dose of previously administered carboplatin was higher in patients who had 3 episodes of anemia (P = .102). In sub-study, 12 had data on folic acid and vitamin B12 levels. Sub-study analysis showed that none fulfilled the criteria for deficiency of folate or vitamin B12, while 3 developed grade 3 anemia. This study revealed that olaparib-induced anemia frequently occurs as macrocytic and normocytic erythroblastic anemia without folate or vitamin B12 deficiencies. A high cumulative dose of previously administered carboplatin and dysgeusia may be associated with olaparib-induced anemia.

Positive Ascites Cytology, Postoperative Chemotherapy and Prognosis of Stage I Ovarian Clear Cell Carcinoma.

BACKGROUND/AIM: Ovarian clear cell carcinoma (CCC) is associated with a poor prognosis and is resistant to chemotherapy. The aim of this study was to investigate the prognosis of CCC in Mie prefecture and to identify poor prognostic factors. PATIENTS AND METHODS: In this multi-center retrospective study, we analyzed the data of patients with CCC between February 2012 and December 2020. Patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2014 system. Statistical analyses were performed using the Kaplan-Meier method and compared between the two groups using the log-rank test. RESULTS: A total of 112 patients were included and the median follow-up time was 48 months. There was no difference in the prognosis between stages IA, IC1, and IC2. For patients at stages IA, IC1, and IC2, there was no difference in progression-free survival (PFS) and overall survival between the adjuvant chemotherapy and no chemotherapy groups. Median postrecurrent survival was 18 and 20 months in the stages I-II and III-IV groups, respectively. Multivariate analysis revealed that positive ascites cytology (p=0.006) was associated with PFS for patients at stages I-II and that the stage (p=0.039) was associated with PFS for patients at stages III-IV. CONCLUSION: Positive ascites cytology was a poor prognostic factor for patients at an early stage of CCC. Postoperative chemotherapy could be omitted for patients in stages IA and IC1. Relapsed patients did not respond to the standard treatment and had a poor prognosis regardless of the primary stage.

Comparison of surgical outcomes between robot-assisted laparoscopic hysterectomy and conventional total laparoscopic hysterectomy in gynecologic benign disease: a single-center cohort study.

We compared the surgical outcomes of robot-assisted laparoscopic hysterectomy (RAH) and total laparoscopic hysterectomy (TLH). This single-center cohort study compared 139 RAH cases from January, 2017 to September, 2021 and 291 TLH cases between January, 2015 and December, 2020. We retrospectively evaluated surgical outcomes, including total operative time (defined as the time from port wound incision to port wound closure), net operative time (defined as the time from the start of pneumoperitoneum to the end of pneumoperitoneum), estimated blood loss, weight of excised uterus (±adnexa), and overall complications, and the relationship between surgeon experience and operative time, net operative time, and blood loss in RAH and TLH. There was no significant difference in the total operative time between the two groups. Regardless of surgeon experience, the net operative time was significantly shorter in the RAH group than in the TLH group (p <0.001) and the estimated blood loss was significantly lower in RAH cases than in TLH cases (p = 0.01). The net operative time per uterine weight was shorter in the TLH group than that in the RAH group; however, there was no significant difference. RAH resulted in statistically better surgical outcomes in terms of net operative time and blood loss, regardless of surgeon experience. However, net operative time and blood loss also seem to be significantly affected by uterus weight. Large trials are imperative to determine the more effective surgical approach between RAH and TLH for different patient subsets.

Efficacy of a portable interface pressure sensor for robotic surgery in preventing compartment syndrome.

BACKGROUND/OBJECTIVE: This study determines whether the use of a portable interface pressure sensor (Palm Q) for robotic surgery could prevent compartment syndrome. METHODS: In the present single center, non-trial observational study, patients diagnosed with gynecological diseases between April 2015 and August 2020 treated with laparoscopic or robotic surgery were enrolled. We assessed 256 cases involving surgery performed in the lithotomy position with an operative time >4 h. The Palm Q device was placed preoperatively on both sides of the patients' lower legs. The pressure was measured every 30 min preoperatively and intraoperatively and adjusted to ≤30 mmHg. If the pressure reached ≥30 mmHg, the operation was stopped, the patient was repositioned, the leg position was released, the pressure was reduced to ≤30 mmHg, and the procedure was resumed. We compared the maximum creatine kinase levels of the Palm Q and non-Palm Q groups. We also analyzed the correlation between the patients' symptoms postoperatively (shoulder and leg pain) and compartment syndrome. RESULTS: Our data showed that immediate postoperative creatine kinase levels predict compartment syndrome. Propensity score matching of the 256 enrolled patients resulted in 92 cases (46 per group), balanced for age, body mass index, and lifestyle disease. Creatine kinase levels differed significantly between the Palm Q and non-Palm Q groups (p = 0.041). None of the patients in the Palm Q group experienced well-leg compartment syndrome complications. CONCLUSION: Palm Q can potentially help to prevent perioperative compartment syndrome.

Balloon Trocar Is a Suitable Instrument for Retroperitoneal Para-aortic Lymphadenectomy in Gynecologic Malignant Diseases.

OBJECTIVE: To demonstrate the surgical technique of retroperitoneal para-aortic lymphadenectomy to prevent peritoneal rupture in gynecologic malignant disease. In this video, the authors describe how to use a balloon trocar to create a safe and efficient working space without peritoneal rupture. DESIGN: A step-by-step video demonstration of a surgical technique. SETTING: Department of Gynecology and Obstetrics, Mie University, Tsu, Japan. INTERVENTIONS: Para-aortic lymphadenectomy is a part of most gynecologic oncology procedures for primary and recurrent gynecologic malignancies. There are 2 approaches to para-aortic lymphadenectomy: transperitoneal and retroperitoneal approaches. Although there are no significant differences between these approaches (such as in terms of the number of isolated lymph nodes or related complications), they are performed based on the operator's preference. The retroperitoneal approach is an unfamiliar surgical technique compared with usual laparotomy and laparoscopic surgery, and its disadvantages include a steeper learning curve for attaining proficiency. It is also difficult to develop the retroperitoneal space without a peritoneal rupture. In this video, we demonstrate the use of balloon trocars to create a retroperitoneal compartment. The patient was placed in the lithotomy position with the pelvis elevated at 5° to 10°. The left internal iliac approach, which is considered the standard approach, was used in this case (Fig 1). After identifying the left psoas muscles and the ureter crossing the common iliac artery, dissection of the left para-aortic lymph node was initiated (Supplemental Video 1, 2). CONCLUSION: Herein, we demonstrated a successful surgical technique for retroperitoneal para-aortic lymphadenectomy to prevent peritoneal ruptures.

Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Cancer-associated gene analysis of cervical cytology samples and liquid-based cytology significantly improve endometrial cancer diagnosis sensitivity.

To the best of our knowledge, there are no useful screening methods for early detection of endometrial cancer in asymptomatic individuals. The present study evaluated the usefulness of genetic analysis of liquid-based cytology (LBC) specimens by assessing whether pathological genetic mutations detected in cancer tissue sections were detected in LBC specimens from the cervix and uterus. The primary endpoint was genetic analysis of cervical cytology specimens and LBC for the detection of endometrial cancer. Endometrial thickening (>11 mm) assessed using transvaginal ultrasonography was present in 60% of cases and adenocarcinoma assessed using cervical cytology was present in 50% of cases. In 70% of cases, pathogenic mutations detected in cancer tissue sections were also detected in cervical and/or endometrial LBC specimens. The pathogenic variants identified were PTEN in four cases, tumor protein P53, PI3K catalytic subunit α and fibroblast growth factor receptor 2 in two cases each and APC regulator of WNT signaling pathway, KRAS and catenin ß1 in one case each. In the present study, a combination of endometrial thickening assessed by transvaginal ultrasonography, cervical cytology and genetic analysis resulted in a high sensitivity of 90% for detection of endometrial cancer. The combination of these tests is more expensive than conventional methods, but delayed detection of uterine cancer requires multidisciplinary treatment, which increases healthcare costs. Increased spending on early detection of uterine cancer is better economically and may improve patient quality of life.

Efficacy of minodronic acid for the prevention of osteoporosis in premenopausal women with gynaecologic disease who undergo bilateral oophorectomy: a single-centre, non-randomised controlled, experimental study.

We evaluated the efficacy of minodronic acid for osteoporosis prevention after bilateral oophorectomy for gynaecologic disease in premenopausal women. Bone mineral density (BMD) and young adult mean (YAM) data from the lumbar vertebrae and femur and bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5 b (TRACP 5 b) data were obtained for 101 patients. The primary endpoint was the efficacy of minodronic acid for osteoporosis prevention. Fifty-five and 31 patients were assigned to medication and no medication groups, respectively. The decrease in BMD and YAM and the increase in BAP/TRACP-5b were significantly more suppressed in the medication group. There were no significant between-group differences in age at oophorectomy, cancer type, body mass index (BMI), and adjuvant therapy. There were no adverse events due to minodronic acid. Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. Impact statementWhat is already known on this subject? Although the current strategy for osteoporosis prevention after premenopausal bilateral oophorectomy (b-OVX) is hormone therapy (HT), there is no consensus on the treatment duration or adverse events.What do the results of this study add? Therefore, we planned a prospective study to evaluate the efficacy of prophylactic treatment for osteoporosis after b-OVX in premenopausal women with gynaecologic disease using minodronic acid, an oral bisphosphonate, which have a strong evidence of the treatment for osteoporosis. The result showed minodronic acid significantly suppressed the decrease in bone mineral density (BMD) and young adult mean (YAM) and the increase in bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5b (TRACP 5b). Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy.What are the implications of these findings for clinical practice and/or further research? Minodronic acid treatment for osteoporosis prevention after premenopausal b-OVX may be effective as a therapeutic agent after the cessation of HT, or alternative for patients who are contraindicated for HT in breast cancer and thrombosis and should be administered with caution with a history of uterine or ovarian cancer.

Does Vaginal Cuff Creation and Avoidance of a Uterine Manipulator Improve the Prognosis of Total Laparoscopic Radical Hysterectomy for Early Cervical Cancer? A Retrospective Multicenter Study.

Our goal was to compare the treatment outcomes of open-abdominal radical hysterectomy (O-RH) and total laparoscopic hysterectomy (TLRH) with vaginal cuff creation and without using a uterine manipulator in stage IB1-B2 (tumor size < 4 cm) cervical cancer cases. In this retrospective multicenter analysis, 94 cervical cancer stage IB1-B2 patients who underwent O-RH or TLRH in six hospitals in Japan between September 2016 and July 2020 were included; 36 patients underwent TLRH. Propensity score matching was performed because the tumor diameter was large, and positive cases of lymph node metastases were included in the O-RH group due to selection bias. The primary endpoint was progression-free survival (PFS) and recurrence sites of TLRH and O-RH. PFS and OS (overall survival) were not significant in both the TLRH (n = 27) and O-RH (n = 27) groups; none required conversion to laparotomy. The maximum tumor size was <2 and ≥2 cm in 12 (44.4%) and 15 (55.6%) patients, respectively, in both groups. Reportedly, the TLRH group had lesser bleeding than the O-RH group (p < 0.001). Median follow-up was 33.5 (2−65) and 41.5 (6−75) months in the TLRH and O-RH groups, respectively. PFS and OS were not significantly different between the two groups (TLRH: 92.6%, O-RH: 92.6%; log-rank p = 0.985 and 97.2%, 100%; p = 0.317, respectively). The prognosis of early cervical cancer was not significantly different between TLRH and O-RH. Tumor spillage was prevented by creating a vaginal cuff and avoiding the use of a uterine manipulator. Therefore, TLRH might be considered efficient.

Safety and efficacy of levonorgestrel-releasing intrauterine device in the treatment of atypical endometrial hyperplasia and early endometrial cancer.

AIM: To investigate the recurrence rate, live-birth rate, and treatment outcomes of levonorgestrel-releasing intrauterine device (LNG-IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade-1 endometrial cancer (EC) in patients who desire fertility-sparing treatment and those seeking conservative treatment without fertility preservation. METHODS: We prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG-IUD insertion. RESULTS: The median patient age was 35 (range: 29-39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG-IUD and recurrence was 20.5 (range: 2-30) months. Three of the nine patients had Grade-1 EC, and six had AEH. The response rates to the LNG-IUD in patients with Grade-1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade-1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth. CONCLUSION: LNG-IUD is effective for the management of AEH and EC in young patients who desire fertility-sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6-month treatment), and patients seeking conservative treatment without fertility preservation.

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy.

BACKGROUND/AIM: Adverse events associated with long-term bevacizumab administration for ovarian cancer have been poorly documented in Japan. This study aimed to evaluate the adverse events of bevacizumab combined with chemotherapy for treating primary and recurrent epithelial ovarian cancer in Japan. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed data of patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy between January 2013 and November 2019. Statistical analyses were performed using the Fisher's exact test and Kaplan-Meier method. RESULTS: A total of 46 patients were included and the follow-up time was 30 months. The median duration of bevacizumab treatment was 14 months, and the median total dose of bevacizumab was 247.5 mg/kg. The most common adverse events were hypertension (n=30; 65.2%) and proteinuria (n=24; 49%) in all grades. The onset of hypertension and proteinuria occurred at a median of 2 months and 14 months after treatment initiation in all grades, respectively. Gastrointestinal perforation occurred significantly more frequently in patients with a history of radiation therapy. CONCLUSION: This study included cases of primary advanced and recurrent epithelial ovarian cancer, and had a longer observation period and reported more adverse events of bevacizumab with chemotherapy than previous reports. The administration of bevacizumab therapy in patients with a history of radiation should be carefully considered due to increased chances of gastrointestinal perforation.

Laparoscopic retroperitoneal para-aortic lymph node biopsy in advanced cervical cancer with pelvic lymph node metastases: A single-center prospective study.

AIM: Extended-field concurrent chemoradiation therapy (Ex-CCRT) has been widely used for para-aortic lymph node (PAN) metastases confirmed by radiographic assessment without surgical exploration. The objective of this prospective study was to evaluate the clinical value of laparoscopic retroperitoneal PAN biopsy in locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastases. METHODS: From May 2017 to March 2020, stage IIB-IIIB cervical cancer patients who were diagnosed with PLN metastasis using positron emission tomography-computed tomography (PET-CT) with maximum standardized uptake value (SUVmax) ≥2.0 underwent laparoscopic retroperitoneal PAN biopsy. The radiation fields were extended to PAN areas with pathological metastases. RESULTS: Fourteen patients were diagnosed with cervical squamous cell carcinoma of the International Federation of Gynecology and Obstetrics (FIGO) stage IIB (n = 7) and IIIB (n = 7). The median operating time was 138 min (range, 104-184 min). The median number of harvested PANs was 19 (range, 6-36). Three patients were positive for PAN metastasis on histological analysis. In this study, the sensitivity and specificity of PET-CT were 66.7% and 90.9%, respectively. CONCLUSION: Our study is characterized by the use of more appropriate eligibility criteria for LACC with PLN metastases. Our results revealed that laparoscopic retroperitoneal PAN biopsy may be a useful approach to determine the radiation field for PANs during standard radiotherapy planning.

Effectiveness of Laparoscopic Combined Retroperitoneal and Transperitoneal Approach in Para-aortic Lymphadenectomy for Endometrial Cancer.

BACKGROUND/AIM: This study aimed to compare laparoscopy with laparotomy and evaluate the effectiveness of a laparoscopic combined retroperitoneal and transperitoneal approach for para-aortic lymphadenectomy in patients with endometrial cancer. PATIENTS AND METHODS: In this single-center retrospective study, patients with endometrial cancer who underwent para-aortic lymphadenectomy between December 2016 and November 2019 were analyzed. The patient's clinical and pathologic data were procured from medical records. Statistical analyses were performed using Fisher's exact and the Mann-Whitney U-tests. RESULTS: A total of 37 and 28 patients were included in the laparoscopic and laparotomy groups, respectively. The laparoscopic group had similar operative time, similar number of resected para-aortic and pelvic lymph nodes, less intraoperative blood loss and complications, lower rate of blood transfusion, and shorter postoperative stay than the laparotomy group. CONCLUSION: Laparoscopic combined retroperitoneal and transperitoneal approach for endometrial cancer is safe and effective compared to laparotomy.

Prognostic Benefit of ≥6 Cycles of Neoadjuvant Chemotherapy for Advanced Ovarian, Tubal, and Peritoneal Cancers.

BACKGROUND/AIM: A higher number of neoadjuvant chemotherapy (NACT) cycles translate to a lower risk of morbidity and mortality, but few studies have analyzed the prognostic impact of >4 cycles of NACT. PATIENTS AND METHODS: Overall, 52 patients [31 patients, NACT plus interval debulking surgery (IDS); 21 patients, NACT alone owing to progressive disease] who underwent NACT between January 2008 and December 2014 were evaluated. RESULTS: In total, 6, 7-10, and 11-18 cycles of NACT were performed in 52.3%, 27.3%, and 20.5% of the patients, respectively. The median overall survival was 76.0 months (range=36.0-94.0 months), and the median progression-free survival was 26.0 months (range=18.0-54.0 months) in the NACT plus IDS group. CONCLUSION: At least six cycles of NACT plus IDS are associated with a lower rate of multi-organ resection and a high rate of complete resection or optimal (<1 cm) following IDS.

Laparoscopic Versus Robotic Hysterectomy in Obese Patients With Early-stage Endometrial Cancer: A Single-centre Analysis.

BACKGROUND/AIM: To compare the surgical outcomes of robotic and laparoscopic hysterectomy with or without pelvic lymphadenectomy among obese patients [body mass index (BMI) >30 kg/m2] with early-stage endometrial cancer. PATIENTS AND METHODS: We examined 42 obese patients with early-stage endometrial cancer who underwent laparoscopic (LH) or robotic hysterectomy (RH) between April 2014 and April 2020 in our institution. We analysed intraoperative and postoperative data for both procedures. RESULTS: Of the 42 women, 22 and 20 patients underwent RH and LH, respectively, with or without pelvic lymphadenectomy. The operation times, harvested lymph nodes, and BMI did not differ between the groups. In the subset of patients who underwent pelvic lymphadenectomy, those in the RH group had shorter hospital stays (p=0.001) and less intraoperative bleeding (p=0.006). CONCLUSION: Obese patients with endometrial cancer who underwent robotic surgery had less blood loss and shorter hospital stays than those who underwent laparoscopic surgery.

Tadalafil treatment for preeclampsia (medication in preeclampsia; MIE): a multicenter phase II clinical trial.

PURPOSE: To evaluate the effectiveness and safety of tadalafil treatment for hypertensive disorder of pregnancy (HDP). MATERIALS AND METHODS: In an open-label, randomized clinical trial, singleton pregnancies with HDP between 20 and 33 weeks of gestation were randomized to take 20 mg oral tadalafil every day (tadalafil treatment group) or no drug (conventional treatment group). The primary outcome was prolongation of pregnancy from randomization to delivery. However, this article primarily focuses on the safety assessments performed in the tadalafil treatment for HDP population, because the safety of using PDE5 inhibitors as therapeutic agents for fetal growth restriction (FGR) has been a problem worldwide. RESULTS: From October 2016 to March 2018, 28 patients were randomized to each group and two cases were excluded (tadalafil treatment group: 12 cases; conventional treatment group: 14 cases). The significant adverse events related to tadalafil did not occur in the tadalafil treatment group. Among maternal adverse events, specifically with regard to headaches, there were significant differences between the two groups (0% in tadalafil group versus 43% in conventional treatment group; p = .02). There was no difference in the prolongation period of pregnancy that served as primary outcomes in both the groups (17.5 d in tadalafil group versus 16.5 d in conventional group, p = .96). The significant adverse events occurred at the same frequency as between the conventional treatment group and the tadalafil treatment group. And, maternal headache decreased significantly in the tadalafil treatment group. CONCLUSIONS: Tadalafil treatment is safe for pregnant women with HDP. Moreover, tadalafil did not prolong the gestational period in pregnant women with HDP.

Dose-dense paclitaxel and carboplatin vs. conventional paclitaxel and carboplatin as neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: a retrospective study.

BACKGROUND: The purpose of this study was to determine the optimal regimen of neoadjuvant chemotherapy (NAC) for advanced epithelial ovarian, fallopian tube, and peritoneal cancers. METHODS: A clinical information survey involving 171 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer was conducted. These patients underwent NAC followed by interval debulking surgery at the Hyogo Cancer Center (Hyogo, Japan) between January 2006 and December 2015. RESULTS: The median observation period was 41 (range 4-138) months. Dose-dense paclitaxel and carboplatin (TC) was administered in 101 patients (59%); tri-weekly TC was administered 70 patients (41%). Median progression-free survival was 21 [95% confidence interval (CI) 18-23] months and 15 (95% CI 13-17) months in the dose-dense TC and conventional-TC group [hazard ratio (HR) = 0.69, 95% CI 0.46-0.96; p = 0.02], respectively. The median overall survival was 59 (95% CI 46-72) and 40 (95% CI 32-57) months in the dose-dense TC group and conventional-TC group (HR = 0.72, 95% CI 0.48-1.06; p = 0.09). Multivariate analysis for progression-free survival demonstrated that dose-dense TC represented an independent prognostic factor (HR = 0.70, 95% CI 0.50-0.99; p = 0.04). CONCLUSIONS: Dose-dense TC is a promising regimen of NAC for advanced epithelial ovarian cancer.

Safety trial of tadalafil administered for the treatment of preeclampsia.

Purpose: The aim of this study is to evaluate the safety of clinical usage of tadalafil in women with preeclampsia.Materials and methods: Maternal, fetal, and neonatal adverse events were closely examined in eight preeclampsia patients receiving tadalafil treatment.Results: There were no maternal adverse events associated with 10 mg/day of tadalafil. Even at 20 mg/day, only grade 1 headaches in two cases and grade 1 palpitation in one case were observed, which resolved spontaneously within 3 days. At a dose of 40 mg/day, there was only one case of grade 1 headache. All these adverse events were grade 1 and spontaneously resolved within 3 days. There were no fetal adverse events. All observed neonatal adverse events were thought to be caused by prematurity and not related to tadalafil.Conclusion: This study shows that tadalafil treatment for preeclampsia is deemed sufficiently tolerable. Although there was a dose-dependent increase in maternal adverse events, all the adverse events were mild and deemed to be safe for the mother and fetus at all dosages.