Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

Clinical relevance of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecology.

This study reviews the progress and recent advances in vaginal natural orifice transluminal endoscopic surgery (vNOTES) as a minimally invasive gynecologic procedure. The proposed advantages of vaginal natural orifice transluminal surgery include enhanced cosmesis due to a scarless procedure, better exposure compared with the pure vaginal approach, tolerable pain scores, fewer perioperative complications, and a shorter hospital stay. Recent advances in surgical instrumentation and technology have improved the feasibility of vNOTES as an innovative treatment option for gynecological conditions. However, technical challenges and training issues must be overcome before its widespread use. As a promising surgical innovation, further randomized comparative studies are required to clarify the safety and effectiveness of vNOTES in gynecology.

Effect and Safety of Diluted Vasopressin Injection for Bleeding Control During Robot-assisted Laparoscopic Myomectomy in Reproductive Women With Uterine Fibroids: A Randomized Controlled Pilot Trial (VALENTINE Trial).

BACKGROUND/AIM: Vasopressin injected during myomectomy is known to effectively reduce bleeding but is sometimes associated with intraoperative vasoconstriction and hypertension due to systemic absorption. Although there is a growing preference for the use of diluted vasopressin, evidence of its effect and safety is still lacking. PATIENTS AND METHODS: We performed a randomized controlled pilot trial to evaluate the effect and safety of vasopressin diluted in a constant volume during robot-assisted laparoscopic myomectomy (RALM), where a total of 39 women with uterine fibroids were randomly assigned into the following three groups (group 1, 0.2 IU/ml; group 2, 0.1 IU/ml; group 3, 0.05 IU/ml with a total of 100 ml of normal saline). The primary endpoint was to compare estimated blood loss (EBL), and the secondary endpoints were to compare postoperative value and drop ratio of hemoglobin, operation time, transfusion, hospitalization, and complications among the three groups. RESULTS: There were no differences in the number and largest size of uterine fibroids, total weight of uterine fibroids, console time, and volumes of intravenous fluid administered during RALM among the three groups, whereas combined operation was performed more commonly in group 2 than in groups 1 and 3 (53.9% vs. 0 to 7.7%; p=0.01). The primary and secondary endpoints were also not different among the three groups. However, two patients in group 1 (15.4%) showed vasopressin-related hypertension. CONCLUSION: Vasopressin diluted in a volume of 100 ml showed an effective hemostatic effect and safety during RALM (Trial No. NCT04874246 in ClinicalTrial.gov).

Optimal Nozzle Position and Patient's Posture to Enhance Drug Delivery into the Peritoneum during Rotational Intraperitoneal Pressurized Aerosol Chemotherapy in a Swine Model.

Even though rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) has been developed to improve the distribution and penetration depth of anti-cancer agents by pressurized intraperitoneal aerosol chemotherapy (PIPAC), the optimal nozzle position and patient's posture have not been investigated. Thus, we used nine pigs weighing 50-60 kg, and sprayed 150 mL of 1% methylene blue as an aerosol through the nozzle, DreamPen® (Dreampac Corp., Wonju, Republic of Korea), with a flow rate of 0.6 ml/min under a pressure of 140 to 150 psi for RIPAC in six and three pigs with supine and Trendelenburg positions, respectively. When we evaluated its distribution and penetration depth, even distribution among 13 regions of the abdomen was observed in three pigs with Trendelenburg position regardless of the depth of the nozzle. Regarding penetration depth, the numbers of regions with maximal penetration depth were high in the 2 cm depth of the nozzle with supine position (n = 5) and the 4 cm depth with Trendelenburg position (n = 3). Conclusively, even distribution and maximal penetration of anti-cancer agents can be expected during RIPAC in the medium depth (4 cm) between the nozzle inlet and the visceral peritoneum located on the opposite side of it and the Trendelenburg position.

Effect and safety of diluted vasopressin injection on bleeding during robot-assisted laparoscopic myomectomy: a protocol for a randomised controlled pilot trial.

INTRODUCTION: Even though the injection of diluted vasopressin into the uterus is expected to reduce intraoperative bleeding with decreased adverse effects during robot-assisted laparoscopic myomectomy (RALM), there is a lack of relevant trials to show its effect and safety. Thus, this study was designed to compare the effect and safety of vasopressin injection on bleedings based on dilution levels of vasopressin with constant volumes during RALM. METHODS AND ANALYSIS: This is a randomised controlled pilot trial, where a total of 39 patients will be randomly divided into three experimental groups in a 1:1:1 ratio. All patients will be classified into the three groups based on the dilution level of vasopressin: group 1-a solution prepared by mixing 20 units of vasopressin with 100 mL of normal saline to make a total of 100 mL; group 2-a solution prepared by mixing 20 units of vasopressin with 200 mL of normal saline to make a total of 100 mL and group 3-a solution prepared by mixing 20 units of vasopressin with 400 mL of normal saline to make a total of 100 mL. During RALM, we will inject diluted vasopressin at different concentrations with a total of 100 mL. As the primary endpoint, estimated blood loss would be compared. As secondary endpoints, we will check the level of haemoglobin and haematocrit, operation time, amount of transfusion, and the period of hospitalisation. In addition, we will check other complications related to vasopressin injection. ETHICS AND DISSEMINATION: This pilot study has been approved by the Institutional Review Board of the Seoul National University Hospital (No. H-2011-107-1174). All potential subjects will be provided written informed consent. The results of this study will be published in peer-reviewed journals and be presented at academic conferences. TRIAL REGISTRATION NUMBERS: NCT04874246 and CKCT0006225.

Is increased chronological age a contraindication to debulking surgery for elderly patients with advanced ovarian cancer?

We collected data of elderly patients aged 65 years and older who underwent debulking surgery for advanced ovarian cancer in order to explore the impact of old age on surgical outcomes and complications. A total of 120 patients were classified as follows: group 1, 65-69 years (n = 58); group 2, 70-74 years (n = 38); group 3, 75-79 years (n = 17); group 4, ≥80 years (n = 7). There were no differences in most of the characteristics, surgical extent and outcomes, and postoperative complications between the four groups, whereas polypharmacy was more common (6 vs. 5-16; p=.02) and operation time was shorter (median, 194 vs. 285-330 min; p=.02) in group 4. Factors related to frailty rather than age, polypharmacy, preoperative albumin level, estimated blood loss and transfusion increased the risk of postoperative complications. Thus, the impact of old age on surgical extent, outcomes and postoperative complications may be minimal in elderly patients with advanced ovarian cancer. Impact StatementWhat is already known on this subject? Optimal debulking surgery is a significant factor in improving the prognosis of ovarian cancer but it is not easy to perform such radical surgery on elderly patients in fear of increasing surgical morbidity and mortality. Some studies suggest that underlying comorbidities may be a stronger contributing factor to increasing such risk rather than old age although there is not enough evidence yet.What do the results of this study add? Through this study, we could see that increased age is not the determining cause of increased morbidity and mortality in elderly patients who undergo optimal debulking surgery in ovarian cancer. There are other aspects describing a patient's health status that can predict prognosis better rather than age.What are the implications of these findings for clinical practice and/or further research? Old age need not be a contraindication when performing optimal debulking surgery in elderly patients with advanced ovarian cancer.

Safety and feasibility of laterally extended endopelvic resection for sarcoma in the female genital tract: a prospective cohort study.

OBJECTIVE: This study aims to evaluate the safety and feasibility of laterally extended endopelvic resection (LEER) for sarcoma in the female genital tract. METHODS: We prospectively recruited gynecologic cancer patients with sarcoma arising from female genital tract who underwent LEER at Seoul National University Hospital from December 2016 to March 2021. Clinicopathologic characteristics, surgical outcomes including postoperative complications and pain control, and survival outcomes of the patients were investigated. RESULTS: A total of nine patients were registered for this study. The median age was 56 years. Carcinosarcoma (n=2, 22%), leiomyosarcoma (n=2, 22%), and undifferentiated uterine sarcoma (n=2, 22%) were common histology types. Complete resection was achieved in 88.9%. The most common location of pelvic sidewall tumors was infra-iliac acetabulum (66.7%). The pathologic outcome showed a median tumor size of 9.0 cm and internal iliac vessel resection with pelvic sidewall muscle was performed in all patients. The median estimated blood loss was 1,600 mL (range, 300-22,300), and the patients were postoperatively admitted to the intensive care unit for median 1 day (range, 0-8). Complete response was observed in 44.4% (4/9) in radiologic studies after LEER, and median progression-free survival, treatment-related survival, and overall survival were 3.3, 19.6, and 98.9 months, respectively. CONCLUSION: LEER was feasible and safe in treating recurrent sarcoma presenting pelvic sidewall invasion with acceptable survival outcomes and manageable postoperative complications.

Rotational intraperitoneal pressurized aerosol chemotherapy with paclitaxel and cisplatin: pharmacokinetics, tissue concentrations, and toxicities in a pig model.

OBJECTIVE: We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. METHODS: We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. RESULTS: Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2-6,237.9) than for cisplatin (0.1-9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. CONCLUSION: Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol.

BACKGROUND: The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. METHODS: This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. DISCUSSION: We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.

Long Non-coding RNA LOC285194 Promotes Epithelial Ovarian Cancer Progression via the Apoptosis Signaling Pathway.

BACKGROUND/AIM: To explore the molecular mechanism and clinical significance of a newly identified lncRNA LOC285194 in epithelial ovarian cancer (EOC). MATERIALS AND METHODS: LOC285194 transcript levels were analyzed in EOC cells compared to normal cells. Small interfering RNAs were used to suppress LOC285194 expression. Levels of apoptosis-related proteins were determined by western blot. LOC285194 expression in ovarian cancer and non-tumor tissues were compared with clinicopathologic and survival data. RESULTS: Knockdown of LOC285194 decreased cell migration and proliferation, enhanced reactive oxygen species production and resulted in increased levels of proteins of the extrinsic apoptotic signaling pathway. LOC285194 expression level was higher in ovarian cancer tissues compared to control. Overall survival was significantly shorter in patients with high LOC285194 expression. Lymph node metastasis and high LOC285194 expression were significant prognostic factors of mortality (HR=4.614 and 5.880; p=0.026 and p=0.002, respectively). CONCLUSION: LOC285194 can promote the progression of EOC via an anti-apoptotic mechanism. It may serve as a novel biomarker for predicting prognosis of EOC.

Hypoxia-induced Maspin Expression Affects the Prognosis of Ovarian Clear Cell Carcinoma.

BACKGROUND/AIM: To investigate the role of the expression of hypoxia-related genes on the prognosis of ovarian clear cell carcinoma (OCCC). MATERIALS AND METHODS: Basal mRNA levels of eight hypoxia-related genes were compared. Cell viability was assayed after treating ES-2 cells under hypoxic conditions. The mRNA and protein levels were evaluated after the induction of hypoxia and administration of increased doses of N-acetylcysteine (NAC). Finally, the prognostic role of their expression levels was evaluated in 61 patients with OCCC. RESULTS: The mRNA and protein levels of maspin increased gradually with the induction of hypoxia. Maspin protein expression decreased after treatment with paclitaxel and NAC. High expression of maspin was related to poor progression-free and overall survival in patients with OCCC (adjusted hazard ratios, 3.97 and 7.47; 95% confidence intervals=1.34-11.81, and 1.98-28.13). CONCLUSION: High expression of maspin induced by hypoxia might be associated with poor prognosis of OCCC.

The Clinical Desire for Pressurized Intraperitoneal Aerosol Chemotherapy in South Korea: An Electronic Survey-based Study.

BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.

Identification of Patients with Recurrent Epithelial Ovarian Cancer Who Will Benefit from More Than Three Lines of Chemotherapy.

PURPOSE: This study aimed to identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Recurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients' survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease or better) and poor response (progressive disease or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated. RESULTS: A total of 189 patients were evaluated. Ninety-four and 95 patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (median, 2.1 months vs. 9.7 months; p < 0.001) and overall survival (median, 5.0 months vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment-free interval (TFI) (hazard ratio [HR], 5.557; 95% confidence interval [CI], 2.403 to 12.850), platinum-resistant EOC (HR, 2.367; 95% CI, 1.017 to 5.510), and non-serous/endometrioid histologic type (HR, 5.045; 95% CI, 1.152 to 22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor response groups (p=0.167). CONCLUSION: Third and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.

Solution to prevent tumor spillage in minimally invasive radical hysterectomy using the endoscopic stapler for treating early-stage cervical cancer: Surgical technique with video.

Gynecologic oncologists had originally preferred minimally invasive surgery (MIS) over laparotomic surgery for patients with early-stage cervical cancer until the Laparoscopic Approach to Cervical Cancer (LACC) trial reported a worse prognosis and more loco-regional recurrence in patients treated with MIS. Although some controversy remains, experts suggested that tumor cell spillage and aggravation may have been caused by intra-corporeal colpotomy, usage of uterine elevators, maintenance of Trendelenburg position, and tumor irritation by capnoperitoneum during surgery. Thus, we introduce a surgical procedure with some steps added to the conventional MIS radical hysterectomy for preventing tumor spillage during the surgery, which is currently being evaluated in terms of safety and efficacy through a prospective, multicenter, single-arm, phase II study, entitled "Safety of laparoscopic or robotic radical surgery using endoscopic stapler for inhibiting tumor spillage of cervical neoplasms (SOLUTION trial: NCT04370496)".

Impact of gynecologic hospitalist on patient waiting time at the emergency department in Korea: A retrospective pre-post cohort study.

OBJECTIVE: This study aimed to identify the impact of care and change in the consultation process given by a gynecologic hospitalist on patient waiting time in the emergency department (ED). MATERIALS AND METHODS: This is a pre-post study that compared patients' length of stay at the ED ten months before and after intervention by the gynecologic hospitalist in 2018. The consultation process changed from ED staff contacting the gynecologic resident (pre-intervention group) to directly contacting the gynecologic hospitalist (post-intervention group). Times elapsed from gynecologic consultation to final disposition, from gynecologic consultation to discharge, and from arrival at ED to discharge were compared between the two groups. RESULTS: Among 945 referrals at the ED during the study period, the number of daytime weekday gynecologic consultations were 68 and 187 cases in the pre-intervention and post-intervention groups, respectively. The time elapsed from gynecologic consultation to the final disposition, the time elapsed from gynecologic consultation to discharge and the time elapsed from arrival at ED to discharge were shorter in the post-intervention group than in the pre-intervention group (median values, 98 vs. 167.5 min, 205 vs. 311.5 min, and 419 vs. 497 min; P < 0.05), and extended length of stay more than 12 h at the ED was less common in the post-intervention group than in the pre-intervention group (9.6 vs. 19.1%; P < 0.01). CONCLUSION: The waiting time of gynecologic patients upon admission and prolonged length of stay at ED significantly decreased after the establishment of the gynecologic hospitalist system.

Knockdown of E2F4 suppresses the growth of ovarian cancer cells through the cell cycle pathway.

Ovarian cancer remains one of the major causes of death from gynecologic cancer in developed countries. The E2F family has been shown to have a central role in the control of cell proliferation, differentiation, and cell cycle progression in various types of cancer. Despite advances in cancer research, the carcinogenic role of E2F transcription factor 4 (E2F4) in ovarian cancer remains unclear. In this study, we investigated the underlying molecular mechanism of E2F4 in human ovarian cancer cells (OCC). E2F4 expression was demonstrated by quantitative real time polymerase chain reaction (qRT-PCR) in OCC. The alterations of expression values were determined using 2(-ΔΔCt) method. The effects of suppressing E2F4 on cell proliferation, migration, and differentiation were evaluated by cell proliferation assay, colony formation assay and wound healing assay in vitro. Overexpression of E2F4 was found at both mRNA and protein levels in OCC. Small interfering RNA was used to suppress E2F4 expression. Depletion of E2F4 inhibited cell proliferation and suppressed the cell migration and colony formation ability compared to controls. The expression of cell cycle machinery including cyclin A, cyclin D and cyclin dependent kinase 2 (CDK2) was increased after E2F4 knockdown. E2F4 modulates ovarian cancer cell proliferation and migration through cell cycle components including cyclin A, cyclin D, and CDK2. Our findings indicate that E2F4 may serve as a valuable candidate and therapeutic target for ovarian cancer treatment in regard to cell cycle control.

SERPINB11 Expression Is Associated With Prognosis of High-grade Serous and Clear Cell Carcinoma of the Ovary.

BACKGROUND/AIM: To evaluate the role of serine protease inhibitor B11 (SERPINB11) expression as a prognostic biomarker in high-grade serous carcinoma (HGSC) and clear cell carcinoma of the ovary (CCC). MATERIALS AND METHODS: We obtained tumor tissues from patients with HGSC (n=145) and CCC (n=59). We evaluated immunohistochemically the expression of SERPINB11 and investigated whether SERPINB11 expression affects platinum-resistance and the prognosis of HGSC and CCC. RESULTS: High expression of SERPINB11 was more common in CCC than in HGSC (57.6% vs. 28.3%; p<0.01), and SEPRINB11 expression did not correlate with platinum-resistance of HGSC and CCC. High expression of SERPINB11 was associated with worse progression-free survival and overall survival with marginal significance in HGSC; no relation between SERPINB11 expression and the prognosis of CCC was found. CONCLUSION: SERPINB11 expression maybe a prognostic biomarker for HGSC.

Comparison of Vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) and Laparoendoscopic Single-Site (LESS) Hysterectomy on Postoperative Pain Reduction: A Randomized Pilot Study.

INTRODUCTION: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy has shown benefit in postoperative pain and operation time compared to laparoscopic hysterectomy in recent studies. However, no prospective studies comparing laparoendoscopic single-site (LESS) and vNOTES hysterectomy have been performed. This study aims to evaluate postoperative pain and safety of vNOTES hysterectomy compared to LESS hysterectomy for benign uterine disease. METHODS: This study is a prospective, investigator-initiated randomized controlled pilot trial. A total of 26 patients were randomized and allocated to vNOTES group (n = 13) and LESS group (n = 13). The primary outcome was postoperative abdominal and vaginal pain evaluated 24 h after surgery. Secondary outcomes included the number of additional analgesics administered and the maintenance rate of patient-controlled analgesia (PCA). RESULTS: No differences were shown in baseline characteristics between the two groups. Operation time was longer in the LESS group (median, 55 vs. 75 min; P = 0.027), and there were no differences in estimated blood loss, postoperative hemoglobin level, surgical indications, and hospitalization days. Postoperative abdominal pain intensity did not differ between the two groups, while the vNOTES group showed higher postoperative vaginal pain than the LESS group at 16 and 24 h after surgery (median, 3 vs. 1 and 2 vs. 0, P = 0.007 and P = 0.010, at 16 and 24 h respectively). No differences were shown in the number of additional analgesics and PCA use between the two groups. CONCLUSIONS: vNOTES hysterectomy can be safely performed for benign uterine disease requiring hysterectomy. However, vNOTES hysterectomy might be associated with higher postoperative vaginal pain intensity compared to LESS hysterectomy. TRIAL REGISTRATION: CRIS identifier KCT0004605.

Preservation of the ovarian reserve and hemostasis during laparoscopic ovarian cystectomy by a hemostatic agent versus suturing for patients with ovarian endometriosis: study protocol for randomized controlled, non-inferiority trial (PRAHA-2 trial).

BACKGROUND: Endometriosis (EMS) can be implanted everywhere, especially in pelvic organs. EMS can be asymptomatic, but it can result in pelvic pain and infertility by inducing local inflammation and pelvic adhesion. The prevalence of EMS is about 10% in reproductive-age women and higher in women with pelvic pain or infertility. For young patients with ovarian EMS, laparoscopic ovarian cystectomy is effective in relieving pelvic pain and preventing local recurrence. However, there is a concern that the ovarian reserve would decrease after the operation because of the removal of a part of the normal ovarian tissue and thermal damage during hemostasis, which depends on the types of hemostasis such as bipolar electrocoagulation, suturing, and the use of a hemostatic agent. In this study, we aim to evaluate the protective effect for the ovarian reserve and hemostasis between a hemostatic agent and suturing during laparoscopic ovarian cystectomy for patients with ovarian EMS. METHODS: This study is a randomized controlled, non-inferiority trial, where a total of 90 patients with ovarian EMS will be randomly assigned to the experimental (hemostatic agent) and control (suturing) groups. In the control group, a barbed suture will be applied for hemostasis, whereas a hemostatic agent will be applied in the experimental group. If two methods are insufficient, bipolar electrocoagulation will be applied for complete hemostasis. As the primary endpoint, the reduction rate of serum anti- Müllerian hormone (AMH) levels reflecting the ovarian reserve will be compared between the two groups 12 weeks after surgery. As secondary endpoints, we will compare the reduction rate of AMH level 48 weeks after surgery, the time required to complete hemostasis, the success rate of hemostasis within 10 min, and adverse events associated with operation. DISCUSSION: We expect that the protective effect for the ovarian reserve and hemostasis may be comparable between the two methods, suggesting that a hemostatic agent may be preferred considering that it is easy to use during laparoscopic ovarian cystectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04643106 . Registered on 22 November 2020.

Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum.

This study aims to evaluate the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs. Because relevant medical devices have not been introduced, we developed our prototype of pressurized intraperitoneal aerosol chemotherapy (PIPAC) and RIPAC by adding a conical pendulum motion device for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate the drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate the tissue concentrations and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via the nozzle, DreamPen® (Dalim Biotech, Gangwon, South Korea), with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars, and capnoperitoneum of 12 mmHg was maintained for 30 min. As a result, RIPAC showed a wider distribution and stronger intensity than PIPAC. Compared with PIPAC, RIPAC demonstrated high values of the tissue concentration in the central, right upper, epigastrium, left upper, left lower, right lower, and right flank regions (median, 375.5-2124.9 vs. 161.7-1240 ng/ml; p ≤ .05), and higher values of the depth of concentrated diffusion and depth of maximal diffusion (median, 232.5-392.7 vs. 116.9-240.1 µm; 291.2-551.2 vs. 250.5-362.4 µm; p ≤ .05) in all regions except for bowels. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no related toxicities. Conclusively, RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.