Comparison of Transvaginal Paracervical and Transperitoneal Approaches in Lymphadenectomy During v-NOTES Surgery for Patients Diagnosed With Endometrial Cancer (ENDONOTE)

The aim of this study is to compare two types of lymphadenectomy (transperitoneal vs. paracervical) during the lymphadenectomy phase of endometrial cancer staging surgery performed using V-NOTES, a new and advanced technique. This study seeks to optimize the V-NOTES technique for endometrial cancer staging. This randomized, prospective, controlled study will include patients diagnosed with endometrial cancer via histology, following physical examination and imaging, and who are electively scheduled for the V-NOTES endometrial cancer staging procedure. Patients will be randomized into two groups: the transvaginal paracervical lymphadenectomy group and the transperitoneal lymphadenectomy group. The parameters related with surgical and functional outcomes will be compared in both groups.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer; Natural Orifice Transluminal Endoscopic Surgery; Sentinel Lymph Node Biopsy; Lymphadenectomy; Minimally Invasive Surgical Procedures
• Intervention / Treatment: Procedure: Transperitoneal lymphadenectomy; Procedure: Extraperitoneal(transvaginal paracervical sentinel lymphadenectomy) group lymphadenectomy

Detailed Description

Surgical staging is often the primary management strategy for endometrial cancer. Sentinel lymph node (SLN) procedures are considered an alternative standard of care in the treatment of significant uterus-confined malignancy. Both accurately estimate nodal status and reduce the surgical morbidity associated with complete lymphadenectomy. Laparoscopic surgery for endometrial cancer has been associated with equal or better quality of life, less blood loss and similar cancer-related outcomes. A new innovation, natural orifice transluminal endoscopic surgery (NOTES), has been developed to further reduce morbidity and scarring associated with laparoscopic surgery. NOTES utilizes the natural orifices of the human body for access to the peritoneal cavity when performing endoscopic surgery.

However, there is no standardization in vNOTES SLN mapping and lymph tracers are diverse. Many procedures and tracers have been reported, such as intra- or retroperitoneal surgery, a range of vaginal surgeries, SLN exposure method, and indocyanine green or methylene blue injection, and they lack comparative studies. This study will evaluate feasibility and surgical outcomes by comparing transvaginal paracervical and transperitoneal mapping in vNOTES hysterectomy with SLN procedure in endometrial cancer.

The study is an observational study with a prospective design. It will be implemented in a single institution, specifically Diyarbakır Gazi Yaşargil Training and Research Hospital, which functions as a tertiary cancer treatment facility.

Between March 2025 and December 2025, patients with newly diagnosed clinical early stage (FIGO 2023 stages 1 and 2) endometrial cancer who will be treated with laparoscopic surgical staging with SLN mapping.

According to inclusion and exclusion criteria, the patients will be randomized into two groups: the transvaginal paracervical lymphadenectomy group and the transperitoneal lymphadenectomy group.

Surgical Procedure of transvaginal paracervical sentinel lymphadenectomy group:

All patients(26) will receive V-NOTES with transvaginal paracervical sentinel lymph node (SLN) mapping followed by V-NOTES hysterectomy and bilateral salpingo-oophorectomy (BSO).

Transperitoneal sentinel lenfadenectomy group's Surgical Procedure:

All patients (26) will receive vNOTES hysterectomy with bilateral salpingo-oophorectomy (BSO) followed by transperitoneal vNOTES sentinel lymph node (SLN) mapping.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kevser Arkan, MD; Phone Number: +905536476838; Email: kevser.toprak1989@gmail.com

Study Locations

• Turkey
  • Baglar
    • Diyarbakir, Baglar, Turkey, 21090
      • Recruiting
      • Gazi Yaşargil Training and Research Hospital
      • Contact: Email: kevser.toprak1989@gmail.com
      • Contact: Sedat Akgol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Patient Selection and Data Collection This study will be implemented in a single institution, Diyarbakır Gazi Yaşargil Training and Research Hospital, which functions as a tertiary cancer treatment facility.

Between March 2025 and December 2025, patients with newly diagnosed clinical early stage (FIGO 2023 stages 1 and 2) endometrial cancer who will be treated with laparoscopic surgical staging with SLN mapping at our institution will be randomized into groups. The research procedure has been approved by the ethics committee/institutional review board of Diyarbakır Gazi Yaşargil Training and Research Hospital and informed consent signed by the patient will be included in each table reviewed.

Eligible participants will be required to give informed consent to participate in the study.

Inclusion criteria will include

• Participants whose endometrial biopsy resulted in endometrial cancer and whose disease will be detected limited to the uterus using imaging modalities (computed tomography [CT], magnetic resonance imaging or Fluorine-18 fluorodeoxyglucose positron emission tomography/CT)
• Absence of synchronous malignancies.
• No neoadjuvant treatment before surgical intervention.

Exclusion criteria will include:

• Contraindications to using methylene blue dye or contraindications to the vNOTES procedure.
• Patients who have had previous malignancy surgery.
• Severe, deeply penetrating endometriosis or enlarged uterus that may require forced vaginal extraction
• Receiving neodajuvant therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Transperitoneal lymphadenectomy; In this arm, patients will undergo transperitoneal lymphadenectomy with V-NOTES. The procedure begins with methylene blue injection for sentinel lymph nodes. Methylene blue will be injected at the 3 and 9 o'clock positions on the cervix, first at a depth of 1 mm and then at 4 mm, with 1 cc administered at each point. This will result in a total of 4 cc (1 cc x 4). Then, the procedure will continue with anterior and posterior colpotomies, followed by placement of the V-NOTES apparatus. Hysterectomy is performed first, followed by peritoneal dissection and lymph node excision.	Procedure: Transperitoneal lymphadenectomy; In this arm, patients will undergo transperitoneal lymphadenectomy with V-NOTES. The procedure begins with anterior and posterior colpotomies, followed by placement of the V-NOTES apparatus. Hysterectomy is performed first, followed by peritoneal dissection and lymph node excision.
Experimental: transvaginal paracervical sentinel lymphadenectomy group; Surgical Procedure of transvaginal sentinel lymphadenectomy group: All patients will be operated in accordance with Memorial Sloan Kettering Cancer Center procedure. V-NOTES will consist of transvaginal paracervical sentinel lymph node (SLN) mapping followed by V-NOTES hysterectomy and bilateral salpingo-oophorectomy (BSO). SLN Mapping: Under general anesthesia, subjects will be placed in supine lithotomy position. Methylene blue solution (BLUMET IV INJECTION INJECTABLE 50 mg/5 ml 1x5 ml) (1 mL submucosal to the cervix at the 3 and 9 o'clock positions and 1 mL at a depth of 1-2 cm, using a total volume of 2-4 mL. Monitoring of lymphatic ducts includes identification of structures stained with methylene blue dye in the expected anatomical location, typically between the internal and external iliac veins or in the obturator region. Bilateral and symmetrical structures believed to be sentinel lymph nodes (SLNs) will be removed. When unilate	Procedure: Extraperitoneal(transvaginal paracervical sentinel lymphadenectomy) group lymphadenectomy; The procedure begins with a vaginal incision in the lateral vaginal fornices (on both sides), which is then extended to allow placement of the V-NOTES apparatus. By identifying an appropriate cleavage plane, the obturator fossa is accessed to excise the obturator lymph nodes. Following this, an anterior colpotomy is performed to access the vesicocervical space, and a posterior colpotomy is made to open the rectouterine pouch. The V-NOTES apparatus is then placed to continue with the hysterectomy and bilateral salpingo-oophorectomy (BSO).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total operation duration	The total duration of the operation in minutes	During surgery
Duration of right and left lymphadenectomy	The duration of lymphadenectomies in minutes	During surgery
number of positive lymph nodes	Sentinel positive lymph nodes in the pathology report	Postoperative second week
Hospitalization duration	Number of days patients stayed at the hospital postoperatively	During hospital stay
Total bleeding volume	Measured by the suction bottle's volume and number of surgical gauzse used during surgery	During surgery
Surgical complications	Clavien dindo scale of surgical complications	During hospital stay
Number of lymph nodes excised	Lymph node count in the pathology report	Postoperative second week
Difference between pre- and postoperative hemoglobin values	Hemoglobin level (g/dL)	Postoperative 1st day
Location o SLN	The area that sentinel lymph node detected internal iliac, external iliac ,bifurcation or obturator fossa	During surgery
Preoperative and postoperative hematocrit values	Hematocrit level (%)	During hospital stay
Tumor's patological features	Histophatology, grade, lymphovascular invasion, tumor diameter(cm), myometrial invasion, stage, total positive lymph node count	Postoperative second week
Management of complications	intraoperative and postoperative complication's management	through study completion
Duration of lateral colpotomy	at transvaginal retroperitoneal procedure ; before the lymphadenectomy we are making and incision to the lateral of cervix .this time describes the time that to reach the obturator fossa to pick the nodes.	During surgery
Duration of hysterectomy	minutes	During surgery
Sentinel lymphnode's side and number	number	Postoperative second week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain	visual analogue scale, higher scores indicate worse pain	3rd and 6th month after operation
6th hour and 24th hour VAS score	The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain."	postoperatively 6th and 24th hours score
Sexual function	assessed by Female Sexual Function Index, higher scores indicate greater satisfaction	at postoperative 3rd and 6th month
Timing of passing gas	Bowel function	During hospital stay
Demographic features	Age, gravidity, parity, previous vaginal delivery, body-mass index	Postoperative second week
Previous abdominal surgery	Medical history	Preoperative day
Initiation of mobilization	After operation the time (hour) that paient is avaliable to mobilize out from the bed	During hospital stay

Collaborators and Investigators

• Sponsor: Saglik Bilimleri Universitesi Gazi Yasargil Training and Research Hospital
• Investigators: Study Chair: Behzat Can, Assoc. Prof., Health Sciences University Gazi Yaşargil Training and Research Hospital; Study Director: Sedat Akgol, Assoc. Prof., Health Sciences University Gazi Yaşargil Training and Research Hospital; Principal Investigator: Kevser Arkan, MD, Health Sciences University Gazi Yaşargil Training and Research Hospital

Publications and helpful links

General Publications

• Deng L, Liu Y, Yao Y, Deng Y, Tang S, Sun L, Wang Y. Efficacy of vaginal natural orifice transluminal endoscopic sentinel lymph node biopsy for endometrial cancer: a prospective multicenter cohort study. Int J Surg. 2023 Oct 1;109(10):2996-3002. doi: 10.1097/JS9.0000000000000551.
• Can B, Akgol S, Adiguzel O, Kaya C. A new, less invasive approach for retroperitoneal pelvic and para-aortic lymphadenectomy combining the transvaginal natural orifice transluminal endoscopic surgery (vNOTES) technique and single-port laparoscopy. Int J Gynecol Cancer. 2024 May 6;34(5):789-790. doi: 10.1136/ijgc-2023-005093. No abstract available.
• Baekelandt J, Jespers A, Huber D, Badiglian-Filho L, Stuart A, Chuang L, Ali O, Burnett A. vNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series. Acta Obstet Gynecol Scand. 2024 Jul;103(7):1311-1317. doi: 10.1111/aogs.14843. Epub 2024 Apr 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: endometrial cancer; sentinel lymph node; lymphadenectomy; extraperitoneal; transperitoneal; V-NOTES
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: ENDOCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication will be shared.
• IPD Sharing Time Frame: It will be shared when the study is published.
• IPD Sharing Access Criteria: When the study is published, the data will be shared by the corresponding author on request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No